MEDICAL PIONEERS

A PIONEERING THERAPY
THAT REWIRES THE IMMUNE
SYSTEM TO FIGHT
LEUKEMIA


7 years old Emily was diagnosed with
the most common childhood cancer,
acute lymphoblastic leukaemia (ALL)
in May 2010. Unfortunately her case,
like 15 per cent of sufferers, was
resistant to traditional treatment.
She was put forward for an
experimental therapy known as
CTL019.
In certain cancers, including the
type of ALL that Emily was battling, a
subset of cells in the immune
system become leukaemia. These
are called B cells.
Another set of cells in the immune
system, called T-cells, normally
recognise and attack invading
disease. But in cancers like ALL, the
abnormal leukemia cells fly under
the radar of the normal T-cells that
are meant to kill them.
In the experimental treatment, her T-
cells were collected from her blood,
then re-engineered in a lab to
recognise and attach to a protein
called CD19 that is found only on the
surface of B cells.
To do this they used a gutted HIV
virus, called a lentivirus, to carry
special receptors into the T-cells.
There is no risk of HIV infection from
a lentivirus.

Source: Daily Mail, UK


The Children's Hospital of
Philadelphia
34th Street and Civic Center
Boulevard
Philadelphia, Pa. 19104 Main
Number: 215-590-1000 Physician
Referral Service: 1-800-879-2467
_____________

MEDICAL PIONEERS

Growing Evidence To
Support Use Of Human Stool
In Treating C. Diff Infection


Clostridium difficile is a deadly bacteria
present in everyone's intestine but in small
numbers, and is kept 'under control' by the
beneficial bacteria in our digestive tracts. But
when we are taking antibiotics, many of the
beneficial bacteria in our intestines are killed,
paving way for Clostridium difficile to multiply
in high numbers, causing infection.
According to the Centers for Disease Control
and Prevention, C. difficile infections are
linked to 14,000 deaths in the U.S. each year.
It is estimated that the infections cost at least
$1 billion in extra health care costs annually.
Fecal transplantation involves taking stool
from a healthy person, diluting it with water
and transferring it into the infected patient's
intestine.
There are a number of ways to perform this
procedure like, nasogastric tube, nasojejunal
tube, upper tract endoscopy, colonoscopy or
retention enema.


In the Henry Ford Hospital study, researchers
evaluated 49 patients who contracted
Clostridium difficile, and treated them with
donated stool from a healthy family member,
either through a nasogastric tube or
colonscopy on an outpatient or inpatient
basis.
The study produced striking results - with 43
of the 49 patients fully recovering with no side
effects. Four patients died of causes
unrelated to Clostridium difficile, one patient
underwent intestinal surgery and one had no
improvement.


Source: RTT News

________________

MEDICAL PIONEERS

Swedish doctors claim
pioneering uterus transplant

In September 2012  a team of researchers at
the University of Gothenburg performed the
world's first mother-to-daughter uterus
transplantation. The procedure was
completed without complications.

Two Swedish women received new wombs
donated by their mothers.
The first patient have had her uterus removed
many years ago because of surgery for
cervical cancer; the other patient was born
without a uterus. Both women, who are in
their 30s, have undergone IVF-treatment well
before transplantation.

The transplantations, which are the result of
more than ten years of Swedish and
international research collaboration, was
completed without complications.

"More than 10 surgeons, that had trained
together on the procedure for several years,
took part in the complicated surgery " says
team leader Mats Brännström, professor of
Obstetrics and Gynecology at the University
of Gothenburg chief physician at the
Sahlgrenska University Hospital Women's
Clinic. "Both patients that received new uteri
are doing fine but are tired after surgery. The
donating mothers are up and walking and will
be discharged from the hospital within a few
days ".

BY: Krister Svahn
+4631 786 38 69

_______________

MEDICAL PIONEERS

In August 2012, surgeons at Emory
University in Atlanta implanted a
second dose of neural cells into a
patient's spinal cord, part of an
experimental treatment aimed at
slowing the progression of ALS, or
Lou Gehrig's disease. The patient,
Ted Harada, is the third person this
summer to receive a second dose
as part of the trial. The cells are
produced by a Rockville, Maryland-
based company called Neuralstem
that isolates stem cells from the
brain and spinal cord of aborted
fetuses. The company is also
targeting other major central
nervous system conditions with its
cell therapy platform, including
spinal cord injury, ischemic spastic
paraplegia, chronic stroke, and brain
cancer.

ALS gradually destroys the
connections between the spinal
cord and motor neurons, eventually
robbing patients of all ability to
move. The hope is that the cells
injected into the spinal cord will
provide support, perhaps by
releasing growth factors, and
prevent motor neurons from dying.
"They nurture the dying motor
neurons back to health or make
them healthier and slow down the
degenerative process," says
Richard Garr, CEO of Neuralstem.

"We have found that the procedure
is extremely safe," says Eva
Feldman, a neurologist at the
University of Michigan and the lead
investigator of the trial. "In a subset
of patients, we seem to see that the
disease is no longer progressing,"
but it is too early to know if the
result from that small number of
patients is meaningful, she says.

Source: MIT Technology Review
_________________

FOR INVESTORS

Megaseller drugs and the ompanies
that make them


On a recently published list of the
fastest growing prescription drugs
the top ten companies are:

Merck (MRK), Vertex (VRTX), Abbott
(ABT), Sanofi (SNY), Eli Lilly (LLY),
Novartis (NVS), Johnson & Johnson
(JNJ), Amgen (AMGN), Novo Nordisk
(NVO) and Regeneron (REGN).

The race was measured by the
absolute  increase in drug sales
worldwide in the first half of 2012
compared to the same period in
2011.

This list of companies could be used
as a basis for an experimental
portfolio to see what effect of
having a fast growing star or stars in
the drug business  have on stock
prices.

Assigning one share of each stock
to the portfolio on January 3rd  2012,
the portfolio value comes to $548.21
and  at the end of the second
quarter it is $698.76, resulting in  a
gain of 23.06%  in   6 months.

Some of the stocks have shown
especially outstanding results.
Regeneron rose 102%, Vertex  
73.50%,  Novo Nordisk 24 %, Abbott
14% in the first half of the year.

At the end of June  Regeneron was
over  the 200 but below the 50 day
simple moving average, all other
stocks were over both.  

These are the superseller drugs:  


(The sales figures were sourced
from company SEC filings,  all
represent  2012 second half
worldwide sales, measured  in
millions of US dollars. Foreign
currencies are converted were
necessary. The sales increase in
percentage is comparing 2012 first
half to the same period in 2011)


Diabetes
Januvia/Janumet from Merck
These drugs are the fastest growing
products in Merck’s portfolio.
Januvia is an oral medicine that
helps control blood sugar levels  for
people with type 2 diabetes.

Janumet contains a combination of
metformin and Januvia. Metformin is
an older drug that works by
decreasing sugar production in the
liver. Janumet is used along with
diet and exercise to lower blood
sugar in adults with type 2 diabetes.
Neither Januvia nor Janumet are  for
treating type 1 diabetes.
Sales:  $2.780 billion,  up 30%


Hepatitis C
Incivek from Vertex
Incivek is an antiviral medication
that prevents certain virus cells
from multiplying in the body. It is
used in combination with
peginterferon alfa or  ribavirin
injections  to treat hepatitis C in
adults.

Incivek, approved in May 2011,
earlier in 2012 eclipsed $1 billion in
total sales, making it the fastest
prescription drug to reach that mark
in pharmaceutical history.
But it must be taken with the
injectable drug interferon and
Incivek's life as a blockbuster is
likely to end once all oral treatment
options become available over the
next two years.
Sales:   $685 million,  up  813%

Arthritis
Humira  from Abbott

Anti-TNF (tumor necrosis factor)  
biologic that dominates the
immunology and inflammation
market.  Humira reduces the effects
of the inflammation  in the body.
Humira is used to treat rheumatoid
arthritis, psoriatic arthritis,
ankylosing spondylitis, and plaque
psoriasis. It is also used to treat
Crohn's disease after other drugs
have been tried without success.

According to Decision Resources  
while Humira will maintain its
dominance among biologics through
2021, sales will start declining  in
2018 due to deeper penetration of
Johnson & Johnson’s Stelara,
competition from new agents, and
the  market entry of biosimilars.
Sales:   $4.259 billion,   up 17%

Diabetes
Lantus  from Sanofi (SNY)

Lantus is a man-made insulin.  It
works by lowering levels of sugar in
the blood. Lantus is a long-acting
form of insulin that is slightly
different from other forms of insulin
that are not man-made.
Lantus is used to treat type 1 or type
2 diabetes.
Sales: $2.896 billion,  up 16.8%.  (EUR
2,346
million)                                                    
    

Depression
Cymbalta from Eli Lilly

Cymbalta is an antidepressant which
affects chemicals in the brain that
may become unbalanced and cause
depression.  Cymbalta is used to
treat major depressive disorder and
general anxiety disorder. It  also
used to treat a chronic pain disorder
called fibromyalgia.
This drug will go generic in 2013.

Sales: $2.338 billion,  up  22%

Multiple  Sclerosis
Gilenya from Novartis

The only oral therapy approved to
treat people with relapsing forms of
multiple sclerosis.

Gilenya capsules intends  to reduce
relapses and delay disability
progression in patients with
relapsing forms of multiple sclerosis
((MS)).
Gilenya is an immunosuppressant. It
works by keeping immune cells
trapped in the lymph nodes so they
can't reach the central nervous
system: brain and spinal cord.
This medication will not cure the
illness, only decrease the frequency
of relapses.

Sales:   $530 million, up  292%

Cancer
Zytiga  from Johnson & Johnson
Prostate cancer pill Zytiga, currently
given after chemotherapy fails,
significantly slows tumor growth,
prevents pain and lengthens life
when used earlier.

In trials, men treated with Zytiga plus
steroids who had not received
chemotherapy gained at least 16
months before the cancer resumed
spreading.
Zytiga was approved by the FDA in
April 2011. The expected approval
for  pre-chemotherapy use would
give Zytiga an advantage as it
competes with Sanofi's Jevtana,  
which had sales of around $50
million  in the first quarter of 2012.
Zytiga sales for the same quarter
were 4 times higher at  $200 million,  
reflecting that  oncologists
preferred to use Zytiga.

Sales:  $432 million,     increase: 700%

Osteoporosis
Xgeva/ Prolia  from Amgen

Xgeva is used to prevent bone
fractures and other skeletal
conditions in people with tumors
that have spread to the bone. Bone
metastases represent a major cause
of pain and suffering in patients with
cancer.
Xgeva is a monoclonal antibody that
targets a protein involved in cancer-
related bone destruction called
human RANKL.
Prolia is another brand used to treat
osteoporosis in postmenopausal
women who have high risk of bone
fracture.
Sale $540 million,  up   190%

Diabetes
Victoza from Novo Nordisk

Victoza is a once-daily injection to
treat type 2 diabetes in some adults.
Victoza is intended to help lower
blood sugar levels along with diet,
exercise, and selected other
diabetes medicines.
Victoza is in a class of medicines
known as glucagon-like peptide-1
(GLP-1) receptor agonists that help
the pancreas make more insulin
after eating a meal.
Victoza is used to treat type 2
diabetes only,  not type 1.
Sales:          $707.93 million  up
73%        (DKK 4.283 billion)

Eye Macular Degeneration

Eylea  from Regeneron is an eye
injection medicine for wet macular
degeneration ((AMD)) which is  a
leading cause of vision loss and
blindness in Americans ages 60 and
older.

The wet form of AMD includes the
growth of abnormal blood vessels.
The blood vessels can leak fluid into
the central part of the retina, also
known as the macula. When fluid
leaks into the macula, the macula
thickens and vision loss occurs.
Eylea works by keeping new blood
vessels from forming under the
retina. It is injected into the eye
either every four weeks or every
eight weeks by an ophthalmologist.
Sales:  $327.5 million,   up 3170%

________________


MEDICAL PIONEERS

Brain Surgery through the
nose
Traditional methods of treating a
ruptured brain aneurysm usually involve
pretty invasive techniques, such as
removing a piece of a patients skull, but
surgeons at the University of North
Carolina at Chapel Hill School of
Medicine have found a new way to stop
the bleeding – and they do it by going
right through the nose.
In a report published in the March 2011
edition of the journal Neurosurgery, Dr.
Anand V. Germanwala and Dr. Adam M.
Zanation describe a case involving
Alfreda Cordero, who was the first person
to undergo this innovative surgery.

Instead of doing open brain surgery or
endovascular coiling, which involves
snaking a catheter through the groin up
to the brain to stop the bleeding –
surgeons opted to thread their tiny
equipment through Corderos' nose to
reach the two aneurysms, which were
located right behind her nasal cavity. The
new approach is called "clipping the
aneurysms through the nose."

UNC School of medicine
email: dom-admin@med.unc.
edu
______
Hospital pioneers wireless
control for incontinence

Millions of patients with incontinence
caused by an overactive bladder can now
use a new wireless device that could solve
the embarrassing condition at the click of
a button - without drugs, needles or
surgery.

The VERV system, which involves a small
patch placed on the lower back and a
remote control, is the first device to halt
the symptoms of overactive bladder
(OAB) syndrome from outside the body
via the wireless technology.
The condition, which occurs when the
bladder muscles contract suddenly or
when the bladder is not full, causes
sufferers to pass small amounts of urine
before they can reach a toilet, or feel a
frequent and urgent desire to urinate.

The system is portable and consists of a
patch, placement tool and a remote
control. The single application patch is
water resistant and designed to be worn
during most normal activities and is
replaced every seven days. The placement
tool helps the patient place the patch
correctly after proper fitting from the
healthcare practitioner. The remote
control is portable and handheld and is
designed to activate and adjust the signal
transmitted by the patch.

It is available in the UK.

Maker:
Ethicon Endo-Surgery
4545 Creek Road  Blue Ash, OH
45242
(513) 786-7000

_______________

MEDICAL PIONEERS

20 month old baby alive
today because her doctor
corrected a birth defect while
still in the womb

About 20 months ago a young
mother, Tammy Gonzalez  in Florida,
midway through her pregnancy, saw
an ultrasound picture on which it
seemed like her unborn baby
blowing a bubble.

Doctors saw a disaster in the
making: a large tumor growing from
the baby's mouth.
There was little chance that the baby
would survive birth.

Tammy did not want to end her
pregnancy, so she sought help from
world-renowned University of
Miami/Jackson Memorial fetal
surgeon Ruben Quintero, M.D., a
pioneer in fetal medicine.

Fetal medicine means  treating birth
defects and high risk conditions
while the baby is still in the womb.

Dr. Quintero explained the risks to
Tammy and agreed to take her case.
In May 2010, Dr. Quintero and
UM/Jackson fetal surgeon Eftichia
Kontopoulos, M.D., operated on
Tammy's baby in utero, using an
endoscope guided by ultrasound.
Using a laser, they resected the
mass and cleared the baby's mouth.
The procedure, in which Tammy was
under local anesthesia and awake,
was done at Jackson Memorial
Hospital and lasted just over an
hour.


Ruben Quintero, M.D
Eftichia Kontopoulos, M.D
University of Miami/Jackson
Memorial Hospital Fetal Therapy
Center,
Miami, FL.


____________

MEDICAL PIONEERS

10 year old girl saved with new
vein grown from stem cells in
Sweden

Doctors in Sweden have replaced a
vital blocked blood vessel in a 10-
year-old girl using the first vein
grown in a lab from a patient's own
stem cells.

The successful transplant operation,
reported online in The Lancet
medical journal in June 2012 , marks
a further advance in the search for
ways to make new body parts.

It could open the door to stem cell-
based grafts for heart bypass and
dialysis patients who lack suitable
blood vessels for replacement
surgery, and the Swedish team said
it is now working with an
undisclosed company to
commercialize the process.

"I'm very optimistic that in the near
future we will be able to get both
arteries and veins transplanted on a
large scale," said Suchitra Sumitran-
Holgersson, professor of
transplantation biology at the
University of Gothenburg, and a
member of the team that performed
the operation in March 2011.
The advantage of using tissue
grown from a patient's own cells is
that there is no risk of organ
rejection and hence no need for
lifelong immunosuppressive drugs.


Phone
031 - 342 10 00
Due to technical adjustments, it may be
difficult to reach our switchboard using the
regular number.
It is also possible to search the switch via
031-343 40 00.
Postal Address
Sahlgrenska University Hospital
413 45 Gothenburg, Sweden


----------------

Surgeons restore some
hand function to
quadriplegic patient

In May 2012 it was reported that
surgeons at Washington University
School of Medicine in St. Louis, MO
have restored some hand function
in a quadriplegic patient with a
spinal cord injury at the C7 vertebra,
the lowest bone in the neck.

Instead of  operating on the spine
itself, the team focused on the
patient's still healthy upper arm
nerves. Bypassing the hand's
original (and now damaged)
connection to the injured spine, the
team effectively used the upper arm
nerves to rewire a fresh connection
to the intact motor control region of
his brain.

These nerves still "talk" to the brain
because they attach to the spine
above the injury.

The surgery was  performed at
Barnes-Jewish Hospital. It was
followed by a one year of intensive
physical therapy. As a result,  the
patient regained some hand
function, specifically the ability to
bend the thumb and index finger. He
can now feed himself bite-size
pieces of food and write with
assistance.

"This procedure is unusual for
treating quadriplegia because we do
not attempt to go back into the
spinal cord where the injury is," says
surgeon Ida K. Fox, MD, assistant
professor of plastic and
reconstructive surgery at
Washington University. "Instead, we
go out to where we know things
work — in this case the elbow — so
that we can borrow nerves there
and reroute them to give hand
function."

Although patients with spinal cord
injuries at the C6 and C7 vertebra
have no hand function, they do have
shoulder, elbow and some wrist
function because the associated
nerves attach to the spinal cord
above the injury and connect to the
brain. Since the surgeon must tap
into these working nerves, the
technique will not benefit patients
who have lost all arm function due
to higher injuries — in vertebrae C1
through C5.

The surgery was developed and
performed by Susan E. Mackinnon,
MD, chief of the Division of Plastic
and Reconstructive Surgery at
Washington University School of
Medicine. Specializing in injuries to
peripheral nerves, she has
pioneered similar surgeries to
return function to injured arms and
legs.

Washington University School of
Medicine in St. Louis
Barnes-Jewish Hospital
1 Barnes Jewish Hospital Plaza
St. Louis, MO
(314) 747-3000

For general information about the
Center for Nerve Injury and
Paralysis or to make an
appointment, please contact
Marci Bailey, RN, MSN, at 314-362-
4598.
______________



Woman Regains Voice After
Not Being Able To Talk For
Past 35 Years
April 2012
A 52-year-old Ohio woman finally got
her voice back after she hit her
throat on the dashboard in a severe
car accident 35 years ago.

Jan Christian broke her neck in four
places during that car accident, and
she was left with a weak voice. Two
years later, she married her
husband, who never really heard
her speak.
However, Christian recently met Dr.
Sid Khosla, an ear, nose and throat
specialist at University Hospital in
Cincinnati – and he was able to fix
her larynx through a series of
operations.

After the surgeries, Christian began
weekly appointments with UC
therapists van Leer and Bernice
Klaben to relearn how to produce
voice. One of her exercises is
designed to narrow the opening of
the vocal tract at the mouth,
creating pressure on the vocal
cords and producing greater
vibration.

Now, Christian is talking more than
ever.

She and her husband have been
married for 33 years and when asked
how he likes her ability to talk she
said, "he thinks it's great, although
he used to joke that he had the
perfect wife, one that can't talk".


Khosla, a professor of
otolaryngology, works with a
research partner aerospace
engineer Ephraim Gutmark.
With $2.5 million in funding from a
National Institutes of Health grant,
the pair have been collaborating on
the causes of voice disorders and
the most effective ways to treat
them.

University of Cincinnati
Dr. Sid Khosla
Dr. Khosla sees patients at
University Pointe with University
Voice & Swallowing Center and
the Medical Arts Building. To
schedule an appointment call,
(513) 475-8400.

231 Albert Sabin Way | Cincinnati,
OH 45267 | (513) 558-4152


____________________
MEDICAL PIONEERS:
Yale doctors fix a little girl's
heart by training her body to
grow new part
March 2012
A 4-year-old girl born with only 1
working heart chamber is
undergoing an experimental new
treatment to grow a new blood
vessel inside her body using a
bioabsorbable tube coated with
stem cells from the girls' own bone
marrow


Four-year-old Angela Irizarry was
born with a single pumping chamber
in her heart, a potentially lethal
defect. To fix the problem, Angela is
growing a new blood vessel in her
body in an experimental treatment
that could advance the burgeoning
field of regenerative medicine.

In August 2011 doctors at Yale
University  implanted in Angela's
chest in a bioabsorbable tube that is
designed to dissolve over time. The
tube was seeded with cells,
including stem cells, that had been
harvested from Angela's bone
marrow.

By March 2012,  the doctors say, the
tube has disappeared, leaving in its
place a conduit produced by
Angela's cells that functions like a
normal blood vessel.
"We're making a blood vessel where
there wasn't one," says Christopher
Breuer, the Yale pediatric surgeon
who led the 12-hour procedure to
implant the device. "We're inducing
regeneration."


Angela's condition, known as
hypoplastic left heart syndrome,
affects some 3,000 newborns in the
U.S. each year. With just one
pumping chamber, or ventricle,
instead of the usual two, the babies
can't deliver sufficient levels of
oxygen to their organs and
extremities,  compromising their
development and causing them to
turn blue and suffer from a lack of
energy. Without a surgical repair,
70% of them die before their first
birthday.

Pediatric surgeons typically treat the
condition with a series of operations
called the Fontan procedure,
designed to enable the heart to
function without the missing
ventricle. The last operation
involves implanting a synthetic
blood vessel made of Gore-Tex to
reroute blood from the lower
extremities directly to the lungs
instead of through the heart. The
device works, but it is prone to
clotting, infection and in some
cases, the need for additional
surgery later in life as the child
grows.

The idea behind Dr. Breuer's project
is that a natural conduit with the
biology of a normal blood vessel
would grow with the child and avoid
or significantly reduce complications
associated with a synthetic tube.

Today, Angela seems more like a
regular kid, says her father, Angel
Irizarry, who works as a carpenter.
"It's a huge difference," he says.
"It's like going from a four-cylinder
to an eight-cylinder car in one
operation."Before the surgery, he
adds, "her eyes weren't as happy as
they are now."

Christopher Kane Breuer, MD
Schedule an Appointment
Appointment Phone
(203) 785-2701
Appointment Fax
(203) 785-3820
Office Phone
(203) 785-2701
Office Fax
(203) 785-3820
christopher.breuer@yale.edu


_______________________
MEDICAL PIONEERS:
FULL GENOME SEQUENCING
HELPS  SOLVE THE
MYSTERY ILLNESS  OF THE
TWINS
March 2012
Noah and Alexis Beery are twins.
They had serious medical problems
since early childhood.

They were diagnosed with cerebral
palsy at age 2,  and with that
diagnosis their parents thought they
had an answer to the problems that
had plagued their twins since birth.
But the case turned out to be more
complicated.

When the twins reached age 4, it
became apparent that the diagnosis
of cerebral palsy did not match the
problems the children were facing.
Their mother did internet research
and found a description of a disease
that fit her daughter's diagnosis
better – dopa-responsive dystonia.

The muscles of people with dystonia
contract and spasm involuntarily. In
this case, the disease was
responsive to a drug called L-dopa,
which substitutes for the
neurotransmitter dopamine that they
lacked. Neurotransmitters are
critical to proper functioning of
nerves that, in this case, control
muscle fibers.

Their doctor started them on small
doses of the drug at age 6, which
alleviated many of their symptoms.
They went to school and began to
function as normal children.

They are now teenagers. Suddenly  
Alexis Beery began to have
breathing problems so severe that
eventually she had  to stop the
athletics she loved. Twice,
paramedics came to the Beery
house because her breathing
problem became acute. Her mother
began another desperate search for
an answer.

Luckily, their father is in the genome
sequencing business.
He is the chief information officer of
Life Technologies Inc., a company
pioneering the research equipment
for next-generation sequencing.

That brought them to Baylor College
of Medicine in Texas  and  to
Richard Gibbs, Ph.D., director of the
Baylor Human Genome Sequencing
Center

There, a team began the search for
the mutated gene that was causing
the twins' problems. Existing single-
gene tests for the two genes known
to cause the dopa-responsive
dystonia were negative. Then the
Baylor team sequenced the whole
genome of each twin (and studied
their parents and brother for
comparison), and  they found the
twins had three genes with
mutations that might be suspect.

Two of the genes had no known
purpose, but one – sepiapterin
reductase, or SPR – had also been
associated previously with dopa-
responsive dystonia.

The twins each inherited two
mutated copies of that gene. One of
the copies came from their mother
and the other from their father. The
mother had a nonsense mutation
and the father had a missense
mutation.


A nonsense mutation stops the
reading of messenger RNA,
resulting in a truncated protein that
does not work.

A missense mutation is a change
that results in the production of a
different amino acid that causes an
alteration in the protein associated
with the gene.

When SPR is mutated, it disrupts a
cellular pathway that is responsible
for not only the production of
dopamine but also two other
neurotransmitters – serotonin and
noradrenalin. Both dopamine and
serotonin act at the synapse, the
junction at which one neuron
passes electrical or chemical signals
to the next.


The result meant that the twins were
not only deficient in dopamine, they
were also deficient in serotonin. In
consultation with the twins'
California pediatric neurologist,
Jennifer Friedman, M.D., of Rady
Children's Hospital in San Diego, the
Baylor doctors at Texas Children's
Hospital advised adding a small
dose of a supplement called 5-HTP
to their medications. Friedman, a
neurologist, had actually treated
another child with the disorder.

"A month after adding the new
therapy, Alexis' breathing improved
dramatically," said Retta Beery, their
mother. "She's been running track
again."

Noah, the brother  has also
benefited, she said. His handwriting
has improved and he was able to
focus more in school.

The Beery case also has important
general implications for studying
human genetics. Each of the Beery
parents has one of the gene
mutations that affected their
children. While the two mutated
genes caused profound disease in
the children, at least one mutation
appeared to be potentially
associated with Retta Beery's
susceptibility to fibromyalgia, which
also affected other members of her
family.

In other words, two mutated copies
of the gene (even when the
mutations are different) cause the
profound disease. A single mutated
copy of the gene may confer
susceptibility to a more common
ailment.


Human Genome Sequencing
Center
Mail: One Baylor Plaza, MSC-226,
Houston, TX 77030
Phone: 713-798-6539 | Fax: 713-
798-5741
E-mail: hgsc-web@bcm.edu
_______________________________



____________
PROMISING TRENDS IN
BRAIN CANCER THERAPY

Glioblastoma Multiforme (GBM) is
a horrible illness and its current
statistics are depressing.

In Europe, two to three people in
100,000 develop glioblastoma
each year. In the United States,
about three new cases per
100,000 are reported anually.
Though rare, glioblastoma is the
most aggressive form of primary
brain tumors and has a poor
prognosis in adults with a two-
year overall survival rate of 27.2%
with standard of care treatment
(radiotherapy plus
temozolomide).  

However, there are promising
new developments.

An initial study of the
experimental ICT-107, a dendritic
cell-based vaccine for the
treatment of GBM, showed 80.2%
of patients were alive at the two-
year mark.

ImmunoCellular Therapeutics,  a
Los Angeles-based oncology firm
and developer of ICT-107,
reported overall survival of 55%;
progression-free survival of 38%,
among patients with this
aggressive form of brain cancer
after three years of study.

Earlier in 2011 the approval of
Dendreon's Provenge vaccine
opened up a trend  toward using
immunotherapy for cancer
treatment and trying to improve
upon  the dismal survival profile
that surgery, radiotherapy, and
chemotherapy offer brain cancer
subjects.

Some other companies are also in
the race.

Genentech, a subsidiary of the
Roche Group, Northwest
Biotherapeutics, and CellDex
Therapeutics among others.

Avastin, Genentech's GBM drug,
has been noted to cause stroke,
blood clot, hemorrhage, and other
serious adverse events.

Maryland-based Northwest
Biotherapeutics is developing
immunotherapeutic DCVax-Brain,
which shares a stark
resemblance to ImmunoCellular
Therapeutics' dendritic cell-based
vaccine. Like ICT-107, DCVax
returned excellent safety data and
a hint of efficacy in treating GBM
in a Phase I study. Survival was
documented at 68% at the two-
year mark; 53% after three years.

CellDex is developing CDX-10
and its latest trial showed overall
survival at 50% after two years,
and median progression-free
survival close to 15 months.
However the trial also generated  
some complaints that  the
requirement of gross total
resection and uncommon EGFR
(+) status left the majority of
patients ineligible for the vaccine.

Some say that Genentech's
Avastin is unlikely to warrant
approval given its overall
risk/benefit profile as a front-line
treatment for GBM. Avastin is
currently approved to treat
recurring GBM.

Cilengitide, developed in Merck
Serono's own laboratories, is the
first in a new class of
investigational anti-cancer
therapies, known as integrin
inhibitors, to reach Phase III
development.

Integrins are cell surface
receptors that are improperly
regulated in many cancer types.
This lack of regulation enables
them to enhance tumor growth,
survival and invasiveness.
Integrins are fundamental in the
process of angiogenesis (blood
vessel growth) – a process that is
essential for tumors as it enables
them to grow past a finite size.

Cilengitide is thought to control
tumor growth by working in two
ways: through attacking the
tumor cells directly in a targeted
manner and through starving
tumor cells by stopping the
formation of new blood vessels
that feed the tumor.

What next in the development
process?

CellDex Therapeutics reported in
August 2011  that the company
would begin enrolling patients in
their Phase III study of
rindopepimut (CDX-10) for newly-
diagnosed GBM in the second
half of 2011.


ImmunoCellular Therapeutics
stated recently that they expect
enrollment for their Phase II trial
to be completed by the second
quarter of 2012.

Northwest Biotherapeutics' last
update told investors that 33 of
240 patients were enrolled in their
pivotal GBM trial.


Merck Serono's CENTRIC is a
randomized Phase III clinical trial
assessing the efficacy and safety
of the investigational integrin
inhibitor, cilengitide, in
combination with standard
treatment (radiotherapy plus
temozolomide, followed by
temozolomide maintenance
therapy) versus standard
treatment alone in newly
diagnosed glioblastoma patients.


Provenge, which serves as a
benchmark being the first FDA-
approved immune therapy, faced
headwinds in sales  lately, related
to its high price.

ImmunoCellular Therapeutics is
one among several firms to
realize far more efficient
manufacturing practices that will
lower the price of its immune
therapy product, once it reaches
the market.

_____________


NEW IDEAS IN DIABETES  
TREATMENT

DIET TO REVERSE DIABETES
It isn't news that weight loss
surgery can correct Type 2
Diabetes in the obese. However,
what is news is that you might be
able to obtain the same results
following a strict diet and skip
surgery entirely.

The idea of the crash diet came
from the observation that gastric
bypass patients often quickly
stopped being
Type 2 diabetics.
Many thought this was because
surgery affected gut hormones
which had a knock-on impact on
the pancreas.
But Prof Roy Taylor of Newcastle
University (UK)  thought it might
really be because the surgery
severely constrained what
patients could eat.

He set up the diet experiment to
test his 'fat' hypothesis.

Prof Taylor asked 11 volunteers,
all recently diagnosed, to go on
what he admitted was an
"extreme diet" of  specially
formulated drinks and non-
starchy vegetables, for eight
weeks of 600 calories a day.

After just a week, pre-breakfast
('fasting') blood sugar levels had
returned to normal, suggesting a
resumption of correct pancreas
function.
After eight weeks, all had
managed to reverse their
diabetes. Three months
on, seven remained free of it.

Prof Taylor explained that too
much fat "clogged up" the
operation of the pancreas at a
cellular level, preventing
normal secretion of insulin which
regulates blood sugar.
When this fat was removed - by
way of the diet - normal function
resumed.

He said special MRI scans
showed the proportion of fat in
volunteers' pancreases dropped
during the eight
weeks, from eight to six per cent.

He said: "This is a radical change
in understanding Type 2 diabetes.
It will change how we can explain
it to people newly diagnosed with
the condition."
"While it has long been believed
that someone with Type 2
diabetes will always have the
disease, and that it will steadily
get worse, we have shown
that we can reverse the
condition."


What does this mean?

It is quite possible that bariatric
surgery isn't the essential
ingredient to reversing Type 2
Diabetes that everyone seems to
believe. The essential ingredient
is  the dramatic, sudden weight
loss and very restricted calories.  

While this low calorie diet is
referred to as "extreme", it  is very
much like what bariatric patients
eat for the first month after gastric
bypass surgery--extremely low
calories mostly consumed in the
form of liquid.

It certainly merits more research.  
If patients can replicate these
results by merely behaving as
though they have had weight loss
surgery, without the actual risks
of surgery, untold millions of
dollars can be saved along with
millions of lives.


AN INEXPENSIVE VACCINE MAY
REVERSE TYPE 1 DIABETES
The first trial in a handful of
humans has suggested that
injecting patients with Type 1
diabetes with an inexpensive
vaccine normally used to prevent
tuberculosis can block
destruction of insulin-secreting
pancreatic cells in humans and
allow regeneration of the
pancreas.

Such a finding, if confirmed and
expanded on, could lay the
foundation for freeing the
estimated 1 million U.S. Type 1
diabetics from their daily insulin
shots. It brings up a word that is
rarely or never used in
considering the disease: "cure."

Such an outcome is still a long
way in the future, but Dr. Denise
Faustman of Massachusetts
General Hospital has already
come a long way in her quest to
find a new treatment paradigm for
diabetes.


The key player in the diabetes
study is a protein of the immune
system called tumor necrosis
factor, or TNF. Studies by others
have shown that if you increase
levels of TNF in the blood, it will
block other parts of the immune
system that attack the body,
especially the pancreas.

To raise TNF levels, Dr. Faustman
her colleagues have been
working with the BCG vaccine,
known formally as Bacille
Calmette-Guerin. BCG has been
used for more than 80 years in
relatively low doses to stimulate
immunity against tuberculosis.
More recently, it has been used in
much higher doses to treat
bladder cancer.


Faustman studied six patients
who had been diagnosed with
Type 1 diabetes for an average of
15 years. They were randomly
selected to receive either two
doses of BCG spaced four weeks
apart or a placebo.

Careful examination of those
receiving the vaccine showed a
decline of T cells that normally
attack the pancreas. It also
revealed a temporary but
statistically significant elevation
of an insulin precursor called C-
peptide, an indication that new
insulin production was occurring


"If this is reproducible and
correct, it could be a phenomenal
finding," said Dr. Robert R. Henry
of UC San Diego. It suggests that
once the destructive immune
response is controlled, the body
has the capability to produce
more insulin, he said.



ARTIFICIAL PANCREAS

Artificial Pancreas Works While
Diabetes Patients Sleep, a Yale
Study Shows.

A computer-controlled device
designed to mimic the human
pancreas by sensing and
regulating glucose controlled the
blood sugar of Type 1 diabetics at
night works better than a
traditional insulin pump.

The study of 12 people showed
that 86 percent of patients using
the so-called artificial pancreas
had blood sugar at recommended
levels at night, according to
researchers at Yale University in
New Haven, Connecticut.

The findings are leading
researchers closer to the goal of
creating a device that can act like
the pancreas, which senses when
the body needs insulin and
delivers it without a person being
aware. Such a device can
improve the ease and
effectiveness of managing blood
sugar, a difficult task that
diabetics must do several times a
day -- before meals, and
sometimes at night.

The patients in the study were
hooked to a Medtronic Inc.
glucose monitor, which sent a
signal to a laptop computer. The
computer ran algorithms to
determine how much insulin, if
any, to release, and then sent a
signal to the patients' insulin
pump while they slept in a
hospital.


At night, patients using the
pancreas-mimicking pump had
blood sugar levels within target
72 percent of the time, compared
with 52 percent of those who
used insulin pumps.

A study published in the British
Medical Journal  found that if an
artificial pancreas were available,
Medicare would save nearly $2
billion over 25 years in costs
related to diabetes complications.


The artificial pancreas would
combine two existing diabetes
technologies—a low blood sugar
sensor and an insulin pump—into
one system that works in tandem,
performing both of these
functions automatically. Several
companies are working to
develop artificial pancreas
devices. Medtronic Inc. already
has a semi-automatic version for
sale outside the U.S. The
combination of these
technologies has the potential to
relieve the burden of constant
blood sugar level monitoring and
lessen the risk of those levels
becoming dangerous.

US Lawmakers at a Senate
Homeland Security and
Government Affairs Committee
hearing asked an FDA official why
a pancreatic pump was available
in other countries but not in the U.
S. and urged the agency to move
its special artificial pancreas
initiative forward.



LONGER ACTING INSULIIN

Longer-acting insulin degludec
cuts nighttime hypoglycemia.

Hypoglycemia is deficiency of
glucose in the bloodstream.


The new longer-acting diabetes
drug insulin degludec (made by
Novo Nordisk) improves long-
term glycemic control with a
lower rate of nocturnal
hypoglycemia compared with
insulin glargine (made by Lantus,
Sanofi-Aventis) in patients with
both type 1 and 2 diabetes,
according to the results of two
recent trials.
________________


PERSONALIZED CANCER
TREATMENT

Cancer patients fare better if they
are diagnosed and treated based on
their tumor's genetic abnormality
rather than its location.
In this vision of the future, a tumor
will not be treated as a breast
cancer or a colorectal cancer; the
tumor will be treated according to
the driver mutations that are found,
and these will be targeted with
mutation-specific drugs.

This approach requires  molecular
profiling.

THE ANDERSON TRIAL
A trial led by University of Texas M.
D. Anderson Cancer Center doctors
suggests so-called targeted drugs,
both experimental ones and existing
ones in new combinations, are more
effective than the one-size-fits-all
drugs routinely given for tumors
found in common parts of the body.

"This study shows the future is
here," said Dr. Razelle Kurzrock,
chair of M.D. Anderson's department
of investigational cancer
therapeutics and the study's senior
author. "In more and more patients,
matching drugs to the genetic
abnormality yields significantly
better responses."

The concept, known as personalized
cancer care, has been touted for at
least a decade, since Herceptin and
Gleevec dramatically improved the
outlook for certain breast cancer
and leukemia patients.
The promised bonanza of targeted
drugs was perceived as slow to
follow, however, and most cancers
are still treated based on which
chemotherapy drug historically has
benefitted the most patients, even
though it's often ineffective with
many of them.

The study involved more than 1,000
M.D. Anderson patients whose
metastatic or inoperable cancer
failed to respond to numerous
conventional therapies.

DNA testing found one or more of 12
molecular aberrations in 460 of the
patients, whose tumors originated in
wide-ranging areas of the body.
The study found that 27 percent of
patients with a gene defect who
were matched to a targeted drug
had significant tumor shrinkage,
more than five times the rate of
patients treated with "non-matched"
therapy. The average survival of
patients treated with a matched drug
was 15.8 months, compared to 9.7
months for those patients not
matched to a targeted therapy.

DNA TESTING IS NEEDED

DNA testing of tumors is mostly done
at academic cancer centers, but its
availability is picking up. For
example at Memorial Sloan-
Kettering Cancer Center in New
York, everyone with metastatic lung
or colon cancer undergoes tests for
dozens of variations that may
influence how they respond to
treatment.

Tyrosine kinases are signaling
molecules that are frequently
mutated.  One of their
responsibilities is regulating a cell's
growth based on the extracellular
signals they receive. The presence
of extracellular growth factors tells
them to induce the cell to grow more
rapidly, while a lack of oxygen or
nutrients tells them to grow more
slowly. When these kinases are
mutated they make the cell grow
uncontrollably, divorcing growth
from the conditions outside the cell.
In some cases, this mutation is what
makes a cell cancerous.

In the 1980s, a mutated kinase was
identified that caused white blood
cells to grow in this uncontrolled
manner and caused chronic myeloid
leukemia (CML). The mutated kinase
is a hybrid formed from two halves
of different proteins that is created
when pieces of chromosome 9 and
12 switch segments in white blood
cells.

The drug imatinib (Gleevec)  was
developed in the 1990s by Brian
Druker of Oregon Health and
Science University and Charles
Sawyers of Memorial Sloan Kettering
to block this mutant kinase, called
BCR-ABL.

In the years that it has been on the
market, Gleevec has transformed
CML from a death sentence to a
manageable condition, with a five
year survival rate exceeding 90%.

Similar fusion genes (and proteins)
have since been found in other
blood cancers but had not been
detected in solid tumors, such as
those affecting the breast, prostate,
colon, lung, and pancreas, thyroid,
kidney and brain. Such solid tumors
account for 80% of cancer deaths in
the U.S. In 2005 Arul Chinnaiyan at
the University of Michigan found the
first gene fusions in a solid tumor, in
prostate tumors.

In Texas polymerase chain reaction
(PCR)-based sequencing,
immunohistochemistry, and
fluorescence in situ hybridization
(FISH) were used to analyze the
tumor tissue for specific
genetic/molecular aberrations.

Initially, the researchers looked for
PIK3CA, KRAS, NRAS, BRAF, EGFR,
CKIT, and PTEN, but then added to
the profile a few more, including
GNAQ, cMET, p53, and ALK.

Molecular aberrations are found in
40% of the tumors; the majority of
these (33%) had 1 aberration. When
considered by cancer type, the most
aberrations were found in melanoma
(73%), followed by thyroid (53%),
colorectal (51%), endometrial (43%)
and lung (41%) cancers.


IT'S NOT A MAGIC BULLET

While the approach may benefit
more patients who enter cancer
studies and speed drug
development, it narrows the number
of people who qualify for
experimental treatment -- and the
potential size of the market.
Historically it has been difficult to
get drug companies to be interested
in this type of approach because it
potentially limits their market. If you
have a drug that works in 10 percent
of the population but you can sell it
to everybody, that has been a widely
successful business model.

On the other hand the targeted
approach may save an experimental
drug from failure.
As an example, initial studies of
Pfizer Inc.'s crizotinib included
patients with any kind of cancer.
Researchers quickly realized that
the three patients who responded to
treatment, out of 37, had a defect in
a gene known as ALK that is key to
the growth and survival of tumor
cells.

The company decided in 2009 to
focus solely on lung cancer patients
with the ALK mutation, a group that
makes up just 5 percent of the lung
cancer population. The bet paid off.
The company filed for regulatory
approval in the U.S. based on its
early trials, with data showing
dramatic response to treatment in
the properly targeted patients.

The executive in charge was
concerned that a drug that could
only benefit 5 percent of patients
might not be commercially viable.
"Fortunately, my colleagues in
commercial development
immediately recognized that, given
the high incidence of non- small-cell
lung cancer, it still accounted for a
considerable number of patients,"
he said.


Matching tumors to treatment isn't a
magic bullet. The treatment stopped
working in the M.D. Anderson trials
after 5.2 months for those getting
targeted care, compared with 2.2
months for patients treated with
unmatched drug therapy.
Which means that a lot more work is
needed.

___________________


ALLERGY SEASON
Some new ideas and some old ones  
revived

What is an allergy?
In the case of seasonal allergies,
pollen gets into the body, and the
body recognizes pollen as foreign
and potentially dangerous.
The body develops an exaggerated
immune response, trying its best to
fight off the pollen invaders.
Typically an allergic reaction is rapid.
The body generates white blood
cells known as mast cells and
basophils. This results in acute
inflammation characterized by
coughing, sneezing, runny nose,
redness of the eyes, and general
malaise.
Pollen allergies are not healthy
reactions. And seasonal allergy
sufferers know only too well that
while they hack, sneeze, wheeze,
cough and run with mucous, others
around them are unaffected. In this
process heredity, gender, race and
age can all play roles.

RUSH IMMUNOTHERAPY
A Dublin doctor in the UK  is taking a
new approach to the misery of
allergy season, providing most of
the needed shots at once, instead of
weekly doses.
Dr. Summit Shah, from Dublin
Methodist Hospital, is using the
technique to immunize patients.
The new approach to allergy
treatment is called rush
immunotherapy.
"Instead of taking 50 shots over the
course of one year, we get through
that same dosage in one day," Shah
said.
The drug-free shots are filled with
tiny amounts of the substance
patients are allergic to, so they will
build up a tolerance to it quickly.
"If you're allergic to, let's say
ragweed, which is coming up this
fall, if you undergo rush therapy
today, by this upcoming fall season,
you'll be symptom free," Shah said.
"This is a lifelong cure."
The shots come once an hour.
In between the staff watches the
patients closely for bad reactions,
and frequently checks their blood
pressure and lung function to make
sure there are no complications.
After the one-day session, patients
need to return for weekly shots for a
couple months, then they should be
allergy-free for the rest of their lives.


ALLERGY MEDICINES DEVELOPED
BY CICASSIA
Cicassia is a UK based allergy
vaccine firm.
It has a   Phase III development
programs for cat and ragweed
allergy therapies, completion of
Phase II testing for house dust mite
and grass allergy T-cell vaccines,
and advancement of development
programs for additional allergy
therapies.

Circassia's T-cell vaccines are based
on its ToleroMune technology.
ToleroMune identifies short peptide
sequences, typically 10 to 20 amino
acids long, from the allergen
proteins that are responsible for
causing allergic reactions in
sufferers. These peptides are
selected for their ability to bind to
multiple major histocompatibility
class II molecules on the surface of
antigen-presenting cells.


DEVICE FOR ASTHMA TREATMENT
In 2010  the U.S. Food and Drug
Administration approved the first
device used in a non-drug
procedure for adults with severe
persistent asthma that is not well
controlled with standard
medications.
The procedure, called bronchial
thermoplasty or "BT" is an out-
patient procedure done by
pulmonologists using thermal
energy to reduce excessive smooth
muscle in the lungs, decreasing the
ability of the airways to constrict and
reducing the frequency of asthma
attacks. This procedure has shown
long-lasting benefits for a subset of
severe asthma patients.
It is estimated that more than 20
million people in the U.S. are living
with asthma, one of the most
common chronic diseases among
children and adults. While most
asthma can be controlled with
medication, an estimated 5-10% of
the asthma population is considered
to have the most severe form of the
disease that doesn't respond well to
treatment. People who have severe
asthma are likely to have more
attacks and are more at risk of a fatal
attack.

In 2010 Boston Scientific
Corporation has acquired  Asthmatx,
Inc., a privately held company in
Sunnyvale, California.
Asthmatx designs, manufactures and
markets a less-invasive, catheter-
based bronchial thermoplasty
procedure for the treatment of
severe persistent asthma in the 6 to
8 million patients 18 years and older
worldwide whose asthma is not well
controlled with drugs (inhaled
medications).


NATURAL REMEDIES
NETTLE
For seasonal allergies, you can turn
to natural remedies that can help
without similar detrimental effects.
A traditional remedy is nettle, Urtica
dioica. Also known as stinging
nettle, this traditional remedy is
safe, inexpensive, non-toxic, and
often highly effective.
Nettle is found profusely throughout
North America, Europe, Asia and
Africa, and has been used for
centuries.
The easiest way to use nettle is as a
tea, though supplements are also
available. Two to three cups daily
will likely improve your condition if
you suffer from hay fever.

EUCALYPTUS
For symptomatic relief of nasal
congestion, eucalyptus is a favorite
remedy.
The eucalyptus tree produces
leaves rich in a natural aromatic oil
that helps to open clogged sinuses
and relieve congestion. It can also
help to curb runny nose and thus
alleviate some of the suffering
caused by hay fever.
One convenient way to employ the
decongesting power of eucalyptus
is with a natural inhaler. The Swiss
company Olbas makes an inhaler
that contains essential oils of
eucalyptus, along with other
aromatic, sinus-opening oils such as
peppermint, cajeput, wintergreen,
juniper  berry and clove.
You can use an essential oil-based
inhaler as often as necessary,
without developing a dependence,
which is common with over-the-
counter nasal sprays.

CAT'S CLAW
Another  way to go in fighting
seasonal allergies is to attack the
problem directly via the immune
system.
A favorite herb for this is the
Amazon plant cat's claw.
Known as an immune modulator,
cat's claw helps to strengthen
immune function in cases where
immune defense is lacking. Cat's
claw accomplishes this by causing
the body to produce more
protective immune factors.
But cat's claw is also a very powerful
anti-inflammatory agent as well, and
thus can help to relieve seasonal
allergic reactions.

HONEY
The theory behind honey is that if
you eat local honey from bees that
live in your area, the nectar created
by the flowers that they draw from
has pollen grains in it that are local
to your area.

VITAMIN C TAKEN WITH QUERCETIN
Vitamin C taken with Quercetin
works in unison to stabilize mast
cells. Mast cells are tiny cells that
line your nasal passages and go
down into your lungs. Basically,
when a mast cell is exposed to a
pollen grain that you're sensitive to,
it releases histamine and causes the
symptoms typical to allergies. By
stabilizing the mast cell, you reduce
its activity so it doesn't release
histamine as easily as it would have.


INHALING STEAM WITH ESSENTIAL
OILS
If you inhale steam with certain
essential oils, you can breathe easily
-- quickly. Bring water to a boil in a
saucepan, turn off the heat and add
4 drops of eucalyptus oil, 1 to 2
drops of tea tree oil and three drops
of rosemary essential oil. The
eucalyptus oil opens up your airway.
The tee tree oil has antimicrobial
properties that align with the
rosemary. The effect won't last for
several hours, but it can provide
immediate relief.

_____________
RACE TO MARKETS

Battle of the
antithrombotic drugs

Plavix, the long time king of
bloodthinners, lost its patent
protection in May 2012. At the
same time the FDA approved
several generic versions.

Evaluatepharma  forecasts sharply
decreasing US  annual sales for  
Plavix:   $2.72 billions for 2012,
$142 millions for 2014 and $76
millions for 2012.  

Antithrombotic drugs can be
separated into those that inhibit
platelet function (antiplatelet
drugs) and those that decrease
the synthesis of coagulation
factors (anticoagulants).

In general, antiplatelet agents are
more effective for the prevention
and treatment of arterial
thromboses (which are platelet
rich), while the anticoagulants are
preferred for treatment and
prevention of venous thromboses
(which usually have few platelets).

The antiplatelet drugs include
aspirin, Plavix from Bristol-Myers
Squibb Co. (BMY) and Sanofi (SNY)
(approved in 1997), Effient from  Eli
Lilly (LLY) and Daiichi Sankyo
(2009), and Brilinta from Astra
Zeneca (AZN) ( 2011).

The anticoagulant agents include
heparin and its low molecular
weight derivatives, such as
enoxaparin (1993); direct thrombin
inhibitors, such as Pradaxa from
Boehringer Ingelheim (2010);  
factor Xa inhibitors, such  as  
Xarelto from Bayer (BAYRY) and
Johnson and Johnson (JNJ) (2011);
Eliquis from Bristol-Myers Squibb
(BMY) and Pfizer (PFE) (waiting for
approval); and the vitamin K
antagonist warfarin (1967).
Anticoagulants are used primarily
in the treatment and prevention of
venous thromboses, but are also
used to treatatrial fibrillation.

The sales results for the first
quarter of 2012, in millions of US
dollars are:
Plavix (still the king in the first
quarter) 1,693 billion,  Pradaxa  
215,  Effient  116 ,  Xarelto 55  and  
Brilinta 9.

But that was before the approval
of Plavix generics.
In May 2012 the FDA approved the
marketing rights for a 300 milligram
version of generic Plavix, known
as clopidogrel,for Dr. Reddy's
Laboratories (RDY), Gate
Pharmaceuticals, Mylan
Pharmaceuticals (MYL), and Teva
Pharmaceuticals (TEVA), and a 75
milligram version for Apotex
Corporation, Aurobindo Pharma,
Mylan Pharmaceuticals, Roxane
Laboratories, Sun Pharma, Teva
Pharmaceuticals, and Torrent
Pharmaceuticals.
Dr Reddy, Apotex, Aurobindo, Sun,
and Torrent are Indian firms.
Generic versions run about a $1 a
day at Walmart and other chain
stores.
Compare thatto brand-name Plavix
at $6.44 per day, $7.68 per day for
Brilinta, and $6.38 for Effient.

With the cheaper clopidogrel
generics available, doctors are
under increasing pressure from
insurance companies to justify the
use of more expensive brands.

Now that alternatives are
available, Plavix does not have the
monopoly power it once had.
For example, Plavix is not
recommended for patients with an
irregular heartbeat, called atrial
fibrillation, who take blood
thinners to prevent strokes. A
2009 report in the New England
Journal of Medicine said patients
with atrial fibrillation who took
Plavix were at an unacceptably
increased risk of severe bleeding.
For patients with atrial fibrillation,
anticoagulants like warfarin
(Coumadin), Pradaxa, and Xarelto
are indicated, and clopidogrel is
not an appropriate substitute.

Another example: About 30% of all
people have a variation in the
gene CYP2C19that limits Plavix's
ability to turn off activated
platelets in the blood vessels and
thus prevent them from forming
clots that can cause a heart attack.
A test that can check for this
genetic variation is available.

However, doctors debate how
useful CYP2C19 really is.

A German study involving 423
patients found that switching  poor
Plavix responders to Effient didn't
affect the number of heart attacks.
The study, published online in
April 2012  by the Journal of the
American College of Cardiology,
enrolled stable patients
undergoing a stent procedure and
the results may not apply to higher
risk patients.


When warfarin alternatives were
first nearing the market,
expectations were high.
Warfarin has a mixed reputation.
Notoriously difficult to dose and
manage, warfarin seemed ripe for
the overtaking, and the market for
new choices was estimated at $10
billion-plus. But as Reuters
reports, doctors are not as
enthusiastic as market-watchers
have been.
Patients taking warfarin require
close monitoring and regular
blood tests as well as dietary and
lifestyle changes.
Pradaxa and Xarelto do not require
regular blood monitoring or
frequent doctor follow-ups, but
patients run a risk of stroke,
serious bleeding, and blood clots
if the medicine is not taken
properly. This is particularly true  
in those with poor kidney function,
because concentrations tend to
build up in their bloodstreams.

There is one key difference
between warfarin and this new
group of rivals. Warfarin's effects
can be quickly reversed with an
antidote: vitamin K. This is not true
of the new drugs--including
Pradaxa, Xarelto, and the standby
Eliquis. As of now there is no
antidote for uncontrolled bleeding.

Pradaxa has had blockbuster sales
worldwide. In the US alone some
2.2 million Pradaxa prescriptions
were written in 2011.
But clouds are gathering.
The nonprofit Institute for Safe
Medication Practices  analyzes the
damage reports made to the FDA.
According to the Institute, in 2011   
Paradaxa  accounted for 3,781
adverse events overall (both
manufacturer and direct reports),
including 542 patient deaths in the
US. That surpasses the notorious
Warfarin (Coumadin),which  
accounted for 1,106 cases of
serious side effects, including 72
deaths.
At least one FDA official believes
that warfarin issues may go
unreported because of its known
risks after years of use.
The makers of Pradaxa and Xarelto
say it takes time for doctors to get
up to speed on new types of
treatments and figure out the best
way to control therisks.
European regulators supported
the company, but  have required
added  warnings about Pradaxa's
bleeding risks to its labeling. FDA
put the drug under a safety review
in December  2011, but affirmed its
risk-benefits balance at the time.

In the meantime lawsuits against
Boehringer are piling up.


Lovenox:  Lovenox, known
generically as enoxaparin, is a
rapid-acting version of heparin, a
widely used blood thinner critical
to millions of heart patients.
The brand name version is made
by Sanofi (SNY).  Lovenox's global
revenue was $4.28 billion in 2010.
In 2011  sales were lower, about   
$2.733 billion, thanks to generic
competition.
In the first quarter of 2012 sales
were down 10.5%  to $701.6 million.

Momenta Pharmaceuticals (MNTA)
is selling its generic drug Lovenox
in partnership with Sandoz, a unit
of Switzerland's
Novartis#HYPERLINK "http:
//public/quotes/main.html?
type=djn&symbol=NVS?
mod=inlineTicker" \t "_blank" AG
(NVS). Sandoz sold $176 million
worth of Lovenox generics in the
first quarter of 2012.

In September 2011 the FDA
approved  another generic
version from Amphastar
Pharmaceuticals  in partnership
with Watson Pharmaceuticals (WPI).
A third company, Teva, is seeking
to sell generic Lovenox, but  the
FDA has not approved it yet.

_________
PCSK9: THE RACE TO
REPLACE STATINS

Statins are the current standard
for cholesterol management and
they are effective.

Yet many patients have problems
achieving their cholesterol goals.
Moreover, some patients are
unable to tolerate statin therapy.

PCSK9 inhibitors are the next big
idea. Besides Amgen, several
other companies are working on
developing PCSK9 inhibitors.

The world's biggest drugmakers
are racing to market the first
medicine to tap into a gene
mutation that drops heart-attack
risk by as much as 88 percent.

Normally, the PCSK9 gene creates
a protein that disrupts the ability of
liver cells to remove bad
cholesterol from blood, enabling it
to accumulate. A mutated form of
the DNA found in 3 percent of
people, lowers levels of the
protein, allowing more of the
artery-clogging hormones to be
swept away.


Amgen's experimental AMG 145, a
fully human monoclonal antibody,
is a PCSK9 inhibitor.

In March 2012 Amgen presented
positive data on its
hypercholesterolemia candidate,
AMG145. Results were presented
at the American College of
Cardiology Scientific Session from
a phase Ib study that was
conducted in high cholesterol
patients taking statins.

The phase Ib study was conducted
to evaluate the safety, efficacy and
tolerability of AMG145 compared to
placebo. Results showed that
patients on low to moderate doses
of statin experienced a mean
reduction in LDL-C (bad
cholesterol) levels of up to 75% at
week 6 when administered
AMG145 every two weeks.

In the 51-patient study, patients
receiving monthly injections of
AMG 145 and taking low to
moderate doses of statins had up
to a 66 percent reduction in "bad"
LDL cholesterol by the eighth
week of the study.

AMG145 is currently in a phase II
program consisting of six studies
which will involve about 1,900
patients. The program will not only
evaluate AMG145 plus statins in
patients with or at risk for
cardiovascular disease, it will also
be studied in patients who cannot
tolerate statins.

Other companies pursuing
research on this front are Merck &
Co., Isis Pharmaceuticals Inc. with
partner Bristol-Myers Squibb Co.
and Alnylam Pharmaceuticals Inc.

In July 2011, Pfizer, the world's
biggest drugmaker, began a
second-stage testing of its anti-
PCSK9 antibody,

But ahead of all of them is
Regeneron.
Regeneron is developing its entry,
called REGN 727, in partnership
with French drugmaker Sanofi. The
product, which has completed mid-
stage trials and is heading toward
far larger Phase III studies, has
been considered to be the clear
front runner.

Amgen's drug, AMG 145, is just
entering mid-stage studies and is
considered about a year behind
REGN 727 in development.

Regeneron's second-stage trials
showed that adding their PCSK9
drug to high doses of Lipitor
lowered cholesterol by 65 percent
versus a 17 percent reduction for
high-dose Lipitor alone.

In January 2012 Alnylam
Pharmaceuticals  announced
positive preliminary results from
its ongoing clinical trial of ALN-
PCS, an RNAi therapeutic targeting
PCSK9 for the treatment of severe
hypercholesterolemia. ALN-PCS
demonstrated statistically
significant RNAi silencing of PCSK9
of up to 66% and reductions of up
to over 50% in levels of low-
density lipoprotein cholesterol
(LDL-C), or "bad" cholesterol, a
clinically validated endpoint.

This Phase I study continues with
planned dose escalation.
Additional results of the study are
expected in the first half of 2012.


________
AMGEN LOSES
ANEMIA DRUG
MONOPOLY
In March 2012  the FDA approved  
Omontys from Affymax Inc.

This drug is  a competitor to Amgen
Inc.'s anemia treatments that have
been the only options for patients with
loss of kidney function for more than
20 years.

Omontys, known as peginesatide, has
been cleared  for patients with chronic
kidney disease on dialysis. The drug
will be Palo Alto, California-based
Affymax's first marketed product.

Small and medium dialysis centers are
especially price sensitive. Peginesatide
would be the choice for these dialysis
providers. A key issue will be pricing
and the extent to which Affymax can
grab business from dialysis providers
that have recently endured price hikes
by Amgen, which sells Aranesp and
Epogen.

Dialysis removes toxins from the blood
when kidneys can't.

Amgen's Epogen, approved in 1989,
generated $2 billion in sales in 2011, a
decrease of 19 percent from 2010.
The reason for the slide in sales is
safety concern, such as increased
heart attack risk, and a recent change
in the Medicare payment system.

Anemia drugs built Amgen into the
world's biggest biotechnology
company. In the early 1980s, as a
small start-up, Amgen won a race to
isolate the gene for erythropoietin, or
Epo, a protein produced in the kidneys
that causes the body to produce
oxygen-carrying red blood cells.
Amgen then spliced the human Epo
gene into hamster ovary cells, which
were grown in culture and could churn
out large quantities of the protein to
use as a drug.

Over the years, Amgen has
successfully defended its monopoly in
patent lawsuits against Genetics
Institute, Transkaryotic Therapies and
Roche.

Unlike the drugs found to infringe
Amgen's patent, Omontys is not a
version of the Epo protein made in
living cells. It consists of two small
protein fragments, called peptides, that
are made chemically and do not share
amino acid sequences with Epo,
according to Affymax.

Peginesatide may compete to a lesser
extent with Amgen's Aranesp, which is
primarily used on nondialysis kidney
patients. Aranesp had $2.3 billion in
sales last year.

Amgen, the world's largest
biotechnology company, has deals with
DaVita Inc. of Denver, the largest U.S.
dialysis provider, and Fresenius,
based in Bad Homburg, Germany. The
deal with DaVita is exclusive and for
seven years, while Fresenius's
agreement isn't exclusive and is for an
undisclosed amount of years.

Johnson & Johnson's Procrit, the same
drug as Epogen, is used only in
patients who aren't undergoing dialysis.

In Europe Amgen's patent has expired
several years ago and there are now
near-generic versions of Epogen,
known as biosimilars, on the market.

The medicines are part of a class of
drugs known as erythropoiesis-
stimulating agents that boost
production of red blood cells. The FDA
recommended in June that doctors use
the lowest possible doses of the
agents because of potential heart
risks. The agency in 2006 first warned
that high doses of the anemia drugs
may cause heart attacks and strokes.




_____________
AMYLIN'S DIABETES
DRUG BYDUREON IS  
APPROVED  -
GLP-1 CLASS DRUGS
ARE BATTLEING IT
OUT
In January 2012 Amylin
Pharmaceuticals received FDA
approval for its diabetes drug
Bydureon, setting the stage for a
commercial battle against an
established rival drug from Novo
Nordisk.

Bydureon's U.S. approval comes on its
third attempt.

Bydureon is a longer-acting version of
Amylin's current diabetes drug Byetta
that will compete against Novo
Nordisk's Victoza. Both Bydureon and
Victoza belong to the growing GLP-1
class of diabetes drugs that stimulate
the release of insulin when a person's
blood sugar gets too high. The drug
delivery technology that allows
Bydureon to be injected once a week
comes from Alkermes, which receives
a royalty on Byudreon's worldwide
sales.

Bydureon's main advantage is that
patients only need to inject the drug
once a week. Victoza must be injected
once daily.

Many investors have been less
confident in Amylin's ability to succeed
with Bydureon because the drug's long-
delayed approval has allowed Novo to
gain a strong hold of the GLP-1
market. Amylin must also sell Bydureon
alone in the U.S. following the
departure of its former partner Eli Lilly.
In Europe, where Bydureon is already
for sale, Amylin is seeking a new
marketing partner to replace Lilly's
commercial efforts.

Novo Nordisk's diabetes drug Victoza
has been on sale in the  U.S. market
since February 2010 for treatment of
type-2 diabetes. The once-daily
injected product is just the second
drug in the new-generation GLP-1
category, rivalling Byetta from Eli Lilly
& Co.  and Amylin Pharmaceuticals
Inc.  

GLP-1 is short for glucagon-like
peptide 1, a naturally occuring
compound that works on different
organs to lower the levels of blood
sugar. For overweight diabetics, there
is another benefit: GLP-1 attaches to a
receptor in the brain to decrease
appetite, which over time, leads to
weight loss.


___________________
THE RHEUMATOID
ARTHRITIS  DRUGS
RACE

Twenty years ago, rheumatoid
arthritis was a condition that was
generally progressive, leading to
increased disability and even early
death.

With the advent of newer biologic
therapies approximately 18 years
ago, most patients with rheumatoid
arthritis will eventually achieve
remission.

Drug development for severe
rheumatoid arthritis (RA) has been
one of the most successful and
lucrative areas of drug
development over the last 15
years.

Currently, nine biologics are
approved for  the treatment of
patients who are hard  to treat with
methotrexate and other oral
disease modifying antirheumatic
drugs.

Those nine drugs  generate over
$16 billion in worldwide sales each
year for various autoimmune
conditions,  approximately ¾ of
which is due to use by RA
patients.

Five the drugs are TNF inhibitors :
Enbrel,  Humira,    Remicade,    
Cimzia,   Simponi

For patients who respond
inadequately to TNF inhibitors,
rheumatologists have four further
options:
Orencia,   Actemra,   Rituxan,
Kineret

But new drugs are on the horizon.

One of the newer class of
compounds that will be arriving on
the biologic scene are the protein
kinase inhibitor drugs. An example
is the JAK - 3 group. These drugs
block the signaling that occurs
between the surface of immune
cells and the nucleus of those
cells. The end result is a
"crippling" of the ability of the
immune cell to over react.

These new drugs hold the hope
for efficacy and  safety similar to
biologics with the convenience of a
once or twice daily pill.

Pfizer's JAK inhibitor  tofacitinib is
the most advanced. Its robust
phase III program has generated
promising  results.

In September 2011 Pfizer said its
experimental drug tofacitinib was
comparable to Abbott Laboratories'
blockbuster Humira in treating
rheumatoid arthritis in a clinical
trial, but associated with a higher
rate of serious adverse health
problems.

Pfizer also said an analysis showed
that death rates across clinical
trials of tofacitinib were in line with
those reported for certain other
rheumatoid-arthritis treatments
including Humira.

Tofacitinib is an oral pill that Pfizer
hopes can be an alternative to
injectible and infused rheumatoid-
arthritis drugs, including Humira.
Analysts are predicting annual
sales approaching $2 billion if it
reaches market. Pfizer submitted it
for regulatory approval, FDA action
date set for August 2012.

Behind tofacitinib are several
other oral kinase  inhibitors,
including Rigel and Astra Zeneca's
SYK  inhibitor fostamatinib
(beginning phase III) and two
phase II JAK inhibitors, one from
Vertex and one  from Lilly/Incyte.

At least thirty biologics are in
clinical trials for RA,  including
seven IL6 inhibitors that, if
approved, will  compete directly
with Actemra.

IL6 inhibitors  beginning phase III
or completing phase II are being
developed by Bristol-Myers
Squibb / Aldor, UCB, Johnson &
Johnson, and Regeneron / Sanofi.

A German company, 4SC  is
developing Vidofludimus, currently
in Phase 2. It is a so-called small
molecule, a drug manufactured by
chemical reactions in large vats,
like most pills. The medicine works
through two channels: It stops
certain immune cells linked to the
rheumatoid arthritis from
multiplying, and dulls some cellular
communication, calming the body's
immune reaction.

Vidofludimus is an oral, lower-
priced alternative to injected
therapies such as Enbrel.

_______________
STEM CELL RACE

In November 2011 US biotech
company Geron announced that it is
leaving the field of stem cell research.

Elsewhere however  stem cell therapy
is gaining credibility  as  real clinical
data starting to show up.

Aastrom Biosciences Inc recently
presented promising results from a mid-
stage trial of its treatment for patients
with critical limb ischemia, a disease in
which blood flow to the extremities is
restricted.

A mid-stage trial from Australia's
Mesoblast Ltd showed its stem cell
product reduced the rate of heart
attacks and the need for artery
clearing procedures by 78 percent.

Shire Plc said in May 2011 that it
planned to establish a new
regenerative medicine business, and
kick-started it with the $750 million
purchase of Advanced BioHealing Inc,
which makes a skin substitute for
treating diabetic foot ulcers.

Amorcyte is intent on developing
patients' own enriched bone-marrow
stem cells as a treatment for
cardiovascular disease. The idea is to
infuse the stem cells into the heart a
week or so after a severe heart attack,
where they will linger and help restore
damaged tissue.
In December 2010 the company
reported promising  results   of a
clinical trial evaluating its lead product
candidate, AMR–001 for the treatment
of damaged heart muscle following
acute myocardial infarction (AMI).

There are going to be dividing lines in
the industry between autologous and
allogeneic and there are some
indications where one will be better
than the other.


Some companies, such as Celgene
Corp, Pluristem Therapeutics Inc,
Athersys and Mesoblast are
developing so-called allogeneic
products designed to be sold with the
ease and scale of a traditional
pharmaceutical. Cells are taken from a
single donor, expanded, frozen and
shipped for use in thousands of people.

Aastrom, Baxter, NeoStem and Cytori
Therapeutics Inc use cells taken from
a patient's own body in what is known
as an autologous transfer. This
personalized approach eliminates the
risk that the cells will be rejected.

Different types of stem cell are being
used for different diseases. Cytori is
developing a heart disease product
derived from fat cells, for example,
while Celgene is using placental cells
for Crohn's disease and rheumatoid
arthritis therapies.

Fetal cells are also being explored.
Neuralstem Inc, for example, is
developing treatments for neurological
disorders from an aborted fetus and is
in the early stages of testing a
treatment for amyotrophic lateral
sclerosis, known also as Lou Gehrig's
disease.

Companies with credible partners will
likely have an advantage. Athersys
has a partnership with Pfizer; Cytori
has a partnership with General Electric
Co; Pluristem has a partnership with
United Therapeutics Corp. Celgene,
which makes cancer drug Revlimid,
has resources of its own.


______________

PROSTATE CANCER
DRUGS

In the treatment of prostate cancer,
70% of men who are diagnosed can
be cured with radical prostatectomy
surgery or radiation therapy. The
remaining 30% go on to hormone
therapy which lowers levels of
testosterone in the body to
castration levels. All of these
patients will eventually become
resistant to hormone therapy and
progress to metastatic disease. It is
at this stage of the disease that
Provenge can play a role.

Before Provenge, the only course of
treatment available after hormone
therapy failed was chemotherapy.
Oftentimes, patients who became
castration resistant would go
untreated until they began to show
the symptoms of the disease which
was pain resulting from metastases
to the bone.

Johnson & Johnson's Zytiga and
Medivation's MDV3100 have both
shown impressive results for
patients who have failed
chemotherapy. This is the patient
population in which Zytiga is now
being used and it will be the initial
market for MDV 3100. However, both
of these products will also go on to
be marketed in the same patient
group in which Provenge is now
indicated; castration resistant
patients with metastases who have
not yet progressed to chemotherapy.

Zytiga and MDV 3100 will probably
be given the same label indication
as Provenge in the 2013-2014 time
frame. This will then present an
issue for doctors on how and when
to use these three agents.




DENDREON'S PROVENGE
Dendreon's drug Provenge was
approved in 2011  and  it works by
stimulating the immune system to
attack the cancer cells. However, it
must be customized to each
individual. Treatment involves
taking white blood cells from a
patient, infusing them with a protein
that identifies prostate cancer cells,
and putting them back into the
patient. Because of the
customization required, treatment is
incredibly expensive. The standard
regimen, which involves three
infusions over a month time frame,
costs about $93,000.



ZYTIGA FROM JOHNSON AND
JOHNSON
The other metastatic prostate drug
currently on the market is Zytiga
from Johnson and Johnson.
Approved in April 2011, the drug
works by inhibiting the enzyme
CYP17 which facilitates the
production of testosterone. These  
are the hormones that stimulate
tumor growth. The drug has to be
taken with prednisone, which can
have major side effects. The drug
costs about $5000/month.




MVD 3100 FROM  MEDIVATION
This drug is still in trials. In
November 2011 the independent
data monitoring committee (IDMC)
had recommended ending the phase
3 trial early due to extremely
positive efficacy. The drug works on
the same principle as Zytiga,
working to prevent androgen from
stimulating tumor growth. However,
instead of blocking the production
of androgen, MDV 3100 blocks the
cellular receptors of the hormone.
By blocking receptors, the drug
inhibits the cells from replicating.


CABOZANTINIB FROM EXELIXIS
Cabozantinib, which is also in trials,
is designed to prevent and shrink
existing bone metastases by
blocking the MET and VEGF
signaling pathways. Bone
metastases are very common in
prostate cancer, occurring in 90% of
patients with castration resistant
prostate cancer. The metastases
can be very painful and are difficult
to target through traditional
radiation and chemotherapy.
Amgen's Xgeva (denosumab) has
been on the market since 2010 for
the treatment of the bone pain
caused by tumors, but has no
known impact on the cancer itself.

Cabozantinib is just entering phase
3 trials and since it was denied
Special Protocol Assessment (SPA)
by the FDA in November 2011, it is
likely to be two to three years before
any results are available.


CURTIRSEN FROM ONCOGENEX
AND TEVA
Another prostate drug currently in
phase 3 trials is Curtirsen (OGX-
011), a joint venture between
OncoGeneX and Teva
Pharmaceuticals. The drug,
currently in two different phase 3
trials, works to block the production
of the protein clusterin. Clusterin is
a cell survival protein that is
overproduced in many different
tumors. The protein, especially in
high quantities, reduces the
efficacy of chemotherapy
treatments. The SATURN trial was
started in March, 2010 with an
expected completion date of June
2013 and the SYNERGY trial started
October 2010 with an expected
completion of December 2013.



______________
HEPATITIS C

The hepatitis C race is heating up.

In November 2011 Gilead Sciences
bought Pharmasset for $11 billion in
cash, vaulting Gilead into the lead
to develop the next generation of all-
oral hepatitis C therapies.

Pharmasset is developing oral drugs
for hepatitis C, or HCV, which is
now  treated by injections. Gilead
made its largest purchase ever after
setbacks with GS 6620, the
company’s own hepatitis C drug
under development which does not
show much promise.

What Pharmasset has is potentially
the first all-oral hepatitis C
treatment. The company plans to
apply for US approval of its
experimental drug, PSI-7977, in the
second half of 2013.  

Companies including Inhibitex Inc.  
and Achillion Pharmaceuticals Inc.
are also racing to develop medicines
for the virus.

Roche Holding AG, based in Basel,
Switzerland, agreed in October 2011
to buy Anadys Pharmaceuticals Inc.,
another maker of experimental
medicines for hepatitis C.

Hepatitis C is a viral infection that
can lead to swelling of the liver. As
many as 170 million people globally
carry the virus, which is transmitted
through exposure to infected blood,
and more than 350,000 die from
related illnesses each year,
according to  World Health
Organization.

The hepatitis C market is currently
about $3 billion worldwide.

Earlier in 2011, Merck & Co. and
Vertex Pharmaceuticals Inc.  won
approval for the first new therapies
for hepatitis C in almost a decade.

In May 2011 FDA approved Incivek
(telaprevir) by Vertex Pharma.

Also in May 2011 FDA approved
Victrelis (boceprevir)  by Merck.

Vertex Pharmaceuticals Inc's  new
hepatitis C drug stormed out of the
gate, and as of July 2011 posting
sales  of nearly $75 million in its first
five weeks on the market.

Incivek  is likely to become part of
the standard of care for hepatitis C
and widely expected to become a
multibillion-dollar seller.

More than 3,000 patients had
started  therapy in the US with
Incivek by mid- July 2011 with a
broad mix of previously untreated
patients and those who failed to be
cured by older drugs.

Incivek prescriptions have been
outpacing Victrelis at a rate of
better  than 3-to-1 in the early
going,  according to data compiled
by Wolters  Kluwer's inThought unit.

Physicians are opting for the drug
that's easier to use and that's
Incivek.




______________
Eye Treatment: Wet
Macular Degeneration

In November 2011 Regeneron
Parmaceuticals  won approval from
the FDA for what is expected to be
its first big drug — to treat the wet
form of age-related macular
degeneration, a leading cause of
severe vision loss in the elderly.

The drug, called Eylea, can be
injected into the eye less frequently
than the current standard,
Genentech’s Lucentis.

Eylea is also slightly less expensive,
at $1,850 an injection versus $1,950
for Lucentis.

Regeneron argues that Eylea would
save the health care system
thousands of dollars a year per
patient, factoring in the fewer
injections and also fewer doctor
visits and examinations.

Eylea, however, is still more
expensive that Avastin, a
Genentech cancer drug that costs
only $50 a dose when used off-label
to treat macular degeneration.

Avastin accounts for more than half
the macular degeneration market,
despite some recent contamination
incidents that have raised safety
concerns.

___________________
SKIN
CANCER/MELANOMA

Zelboraf (Vemurafenib) from
Genentech/Roche/Daiichi Sankyo,  
comes in a pill and was approved in
the US in August 2011, attacks a
genetic mutation found in about
half of melanoma patients,
inhibiting the disease's ability to
spread.

A diagnostic test to determine
whether patients carry the mutation
was approved at the same time.

In March 2011, the FDA approved
another late-stage melanoma
treatment, Bristol-Myers Squibb's
Yervoy, which acts to trigger the
body's anticancer immune response.

Yervoy was found to extend
patients' lives, an improvement over
many current treatments. However,
the drug works for less than 20
percent of patients, and doctors say
they can't predict which patients
will find it most effective.

Zelboraf was clinically effective in
50 percent of patients who had a
specific genetic mutation called
BRAF V600E. Most of the melanoma
therapies work for less than 20
percent of patients.

Both Zelboraf and Yervoy are
expensive. Zelboraf will cost $9,400
a month — $56,000 for a standard
six-month course of treatment,
according to Genentech. Bristol-
Myers said it would charge $120,000
for a complete, three-month course
of Yervoy.

The Melanoma Research Foundation
said they expect insurers to cover
the cost of lifesaving drugs,
especially for cancer patients who
— until now — have had very few
options.

Despite the high price, the impact
might be temporary without the
addition of complementary
treatments. The molecular
mechanisms that have made for
such promising drug targets can
also lead the tumors to develop
resistance to the new treatments.
As a result, companies are
researching the combination of
therapies, including Zelboraf and
Yervoy.

It is hard to see the two drugs as
direct competitors, as they
represent such distinct approaches.
Yervoy, which stimulates the
patient's immune system to fight
cancer cells, rarely leads to
profound tumor shrinkage but
results in prolonged remissions and
perhaps cures in 5-10% of patients.
Zelboraf , on the other hand,
disrupts signaling in cancer cells
and shrinks tumors in the majority
of patients, but durable remissions
are quite rare. One advantage
Zelboraf has is its benign safety
profile compared to Yervoy's
problematic safety profile which
could be fatal in some cases.
Yervoy's biggest advantage is its
intended use for all melanoma
patients. This is in contrast to
Zelboraf , which will be used only in
patients with BRAF mutations (50-
60% of melanoma patients).

Due to the distinct mechanisms,
clinicians will probably use both
drugs when possible. The current
thinking is starting with Zelboraf to
decrease tumor burden and improve
patients' status, and then introduce
Yervoy to achieve maximal effect
and long term remissions. This
hypothesis is yet to be proven, even
though it makes a lot of sense.
___________________



ATRIAL
FIBRILLATION/STROKE
/BLOOD CLOTTING
INHIBITORS

• Pradaxa, from Boehringer
Ingelheim, was approved for sale in
the U.S. in 2010.

• Rivaroxaban (Xarelto), from
Johnson & Johnson and Bayer, is
awaiting FDA approval to prevent
stroke, but It has been approved by
the FDA to prevent deep vein
thrombosis in hip and knee surgery
patients.

• Eliquis (Apixaban), from Pfizer and
Bristol-Myers Squibb, is in Phase 3
of development, it is expected to be
approved by the end of 2011.

• Edoxaban, from Daiichi Sankyo, is
in Phase 3 development, with pivotal
trial expected to completed in 2012.


The team of Bristol-Myers Squibb
and Pfizer may have just cemented
their place atop a new market for
blood thinners that could exceed
$10 billion per year.

Their new pill, Eliquis (generic
name: apixiban), is the first
medicine proved to be both safer
and more effective than warfarin,
an 80-year-old blood-thinner
originally used as rat poison, in
patients with a heart rhythm
disorder called atrial fibrillation,
which raises the risk of stroke five-
fold. It is also the first to reduce the
deaths in a-fib compared to warfarin
by a statistically significant margin.
Eliquis has not yet been approved
for sale by the Food and Drug
Administration.

Those study results, published in
the New England Journal of
Medicine and presented at a medical
meeting in Paris in August 2011, will
give Bristol and Pfizer a big
marketing advantage over two rivals.

One, Pradaxa from Boehringer
Ingelheim, is already on the market
and is being prescribed 7% of the
time among atrial fibrillation
patients.

A second, Xarelto, from Bayer and
Johnson & Johnson, is already on
the U.S. market for preventing blood
clots during some surgeries and is
expected to be approved for atrial
fibrillation later this year.

But neither of those drugs was able
to prove it reduced the number of
deaths compared to warfarin.
Pradaxa was more effective at its
top dose but caused as much
bleeding as warfarin.

________________



BIOSIMILARS

Biosimilars are copies of
complex and expensive biotech
drugs. As the originals come off  
patent protection in the next few
years, it will be a multibillion
dollar industry to copycat them.

The prize is huge. Over the next
decade, patents on biotech
drugs with global sales of 90
billion euros ($127.5 billion) are
set to expire, according to the
European Generic Medicines
Association (EGA), opening the
door to copycat products.

But producing biosimilars is
complicated and expensive.
It is estimated that on average,
biosimilars will require about
$100 million and five to six years
to develop, reflecting the need
for clinical trials to prove safety
and efficacy in regulated markets
such as Europe and the United
States.

So heavywight companies are
moving in  for the business.

In June 2011 Merck & Co
signed  a deal worth up to $720
million with Hanwha of South
Korea for rights to its copy of
Amgen's best-selling arthritis
drug Enbrel, which is given by
injection. Hanwha Chemical is a
petrochemicals group.

Update: In November 2011  
Amgen announced the issuance
of a new composition of matter
patent (#8063182) by the US
Patent Office  related to Enbrel,
which describes and claims the
fusion protein that is etanercept
and has a 17-year term from this
year (or to 2028).
This may substantially delay the
biosimilar's launch in the US.

Earlier in 2011 Samsung, South
Korea's largest conglomerate,
set up a joint venture with
pharmaceutical services
provider Quintiles to contract
manufacture biotech drugs.

Celltrion and LG Life Sciences
are other South Korean players
with global ambitions in
biosimilars, Dr Reddy is from
India. Also players are Israel's
Teva and Sandoz, the generics
unit of Switzerland's Novartis as
well as Big Pharmas like Merck
and Pfizer.

Update: In November 2011
Celltrion Inc. said  it completed
the first successful clinical trial
of a biosimilar antibody drug for
rheumatoid arthritis.

Celltrion said it has tested the
new drug on 874 patients in 20
countries since last November.
It has spent 200 billion won in
the clinical experiments so far
and plans to spend another 80
billion won.
“It demonstrated equivalence in
our initial review of the clinical
and paraclinical trials. No
physical or chemical problems
were found in the 35 categories
of quality,” a Celltrion official
said in a press conference in
Seoul.

Celltrion’s success is a
biosimilar version of Johnson &
Johnson’s Remicade, the global
sales of which amounted to
about 7 trillion won last year.
“We plan to begin sales of the
product after getting approval
from the Korea Food and Drug
Administration within the first
half of 2012,” the company
official said.

Celltrion is also developing a
biosimilar version of the breast
cancer drug Herceptin and plans
to complete clinical trials in mid-
December.

In 2010 Pfizer Inc. and Indian
biotechnology company Biocon
Ltd. agreed to a licensing deal for
the rights to commercialize
Biocon's biosimilar insulin in
both emerging as well as
developed markets. The world's
biggest drug maker will gain
exclusive rights to
commercialize Biocon's
Recombinant Human Insulin,
Glargine, Aspart and Lispro
diabetes-treatment products.

Companies in India, China and
Korea have had products out in
the market for a few years now.
For example Dr Reddy's has
been selling a copycat version of
Roche's Rituxan cancer drug in
India since 2007.

Western markets are further
behind. Europe has approved
two major biosimilar products,
EPO (for chemotherapy and
renal failure)  and filgrastim for
blood disorders, and is
consulting on rules for
antibodies, while U.S. general
guidance on biosimilars are only
due later in 2011.
_______________________

HEART VALVE REPAIR
WITHOUT SURGERY

In August 2011 Medtronic Inc. said
that European regulators have
approved a type of heart valve that
is implanted in the body without
major surgery.

Medtronic's  31-millimeter
CoreValve System received the CE
Mark for sale in Europe. The valve is
the largest available in the world,
and adds to the company's portfolio
of two other sizes of the so-called
transcatheter valves.

The CoreValve system provides a
minimally invasive treatment option
for patients with symptomatic,
severe aortic stenosis, an abnormal
narrowing of the aortic valve, who
cannot tolerate open-heart surgery.

Roughly 300,000 people worldwide
have been diagnosed with the
condition, according to Medtronic.
Since 2007, Medtronic's CoreValve
has been implanted in more than
15,000 people worldwide.

The valve is not available for use in
the United States, and probably
won't be until 2014. The pivotal
clinical trial of the device needed
for Food and Drug Administration
(FDA) approval is underway.

In July 2011, an FDA advisory panel
recommended approval of a similar
valve made by California-based
Edwards Lifesciences. Analysts
expect the Edwards valve to win full
regulatory approval in the United
States by October 2011, with a
market launch shortly after.

Little Canada-based St. Jude
Medical Inc. is also working on a
transcatheter valve. The European
clinical trial for its Portico valve will
begin later this year, with a launch
in Europe expected in the first half
of 2013, pending regulatory approval.

St. Jude will submit an application
to the FDA to begin a clinical trial in
the first half of 2012.

_____________________



___________________

MULTIPLE SCLEROSIS

In August 2011 the UK health-care
watchdog, NICE  recommended
against reimbursing for Novartis
AG's  multiple-sclerosis medicine
Gilenya  because of uncertainties
over the  drug's clinical
effectiveness for certain  patients.

Gilenya, which has been approved
in  the U.S., Europe and elsewhere,
is one  of Novartis's most promising  
medicines, expected to reach
annual  peak sales of more than $3
billion. The  high price of the pill—
more than  $40,000 per patient per
year—has  been considered justified
because it is
easier to use than standard
treatments  that require injections
or infusions.

Gilenya is the first approved
oral
treatment indicated for relapsing
forms  of MS in the US, a major
advance for  people with this
disease.

Gilenya showed superior efficacy
by  reducing relapses by 52% at one
year compared with interferon beta-
1a IM, a commonly prescribed
treatment.

Two-year, placebo-controlled study
showed that Gilenya significantly
reduced the risk of disability
progression.

It has a well-studied safety and
tolerability profile with over 2,600
clinical trial patients.

Gilenya competes  with injectibles
from  Biogen Idec, Bayer, Merck
KGaA, and  Teva Pharmaceuticals.

In June 2011  Merck KGaA of
Germany  abandoned attempts to
market a rival  treatment.

That means Novartis has the only
oral  multiple-sclerosis treatment in
the  market at the moment.

Currently, Teva and its marketing
partner Sanofi-Aventis (SNY) lead
the  market with Copaxone, which
had more  than $2.8 billion in sales
in 2009.

Biogen's Avonex raked in more
than  $2 billion as well, and the
other drugs  in the category
managed to draw sales
over $1 billion each. The side
effects  for these drugs can often be
severe  and the inconvenience and
pain that  comes from daily
injections are  unwelcome to many
patients. Some  analysts estimate
that the market could expand
rapidly if an oral medication is
available just adding those patients
that couldn’t handle the side effects
or  pain of the injectibles.

Biogen Idec Inc. and Abbott
Laboratories in August 2011
reported positive data from
experimental once-monthly multiple
sclerosis drug daclizumab HYP.

Biogen and Abbott’s multiple
sclerosis drug daclizumab has
performed well in a mid-stage trial,
but two deaths marred the overall
results.

The phase IIb study involved
patients receiving daclizumab high-
yield process (or DAC HYP), an
injection which needs to be given
just once every four weeks.

Biogen is a lead player in multiple
sclerosis - Avonex leads the beta
interferon market with $2.5 billion
in sales, while Tysabri
(natalizumab), is co-marketed with
Elan and earned $1.2 billion last
year.

Biogen and Abbott hope the greater
convenience of the new injectable,
twinned with good efficacy can help
it maintain its dominant market
position, but competition is hotting
up.  

Convenience is a factor in the
attraction of daclizumab HYP, which
is given once a month by
subcutaneous injection compared
with once-weekly and once-daily
injections for popular MS
treatments. Although the
improvement is notable, it will have
to compete with the emerging
market for oral MS therapies,
thought to be the most attractive to
patients.

LEMTRADA/ CAMPATH-1H has now
progressed to a phase III clinical trial
(sponsored by Genzyme Inc./Sanofi)
comparing two short courses of
CAMPATH-1H a year apart with
standard beta-interferon injections
in relasping remitting MS patients.
Analysis of the results at 3 years
indicated that CAMPATH-1H
treatment reduced the risk of
accumulating disability by 70%
compared to beta inteferon
treatment.

Campath-1H is a potentially new
treatment for Multiple Sclerosis.  It is
currently (2011) undergoing trials in
the UK, USA, Italy and Croatia to
determine whether it can help those
with an early form of MS. The drug
is a monoclonal antibody designed
to target that part of the immune
system which is assumed to be
harming people with MS.

LAQUINIMOD BY TEVA MAY BE DEAD
In July 2011 Teva Pharmaceutical
Industries Ltd. ’s experimental
multiple sclerosis pill failed to
reduce relapses more than placebo
in a clinical trial, dealing a blow to
the company’s effort to find a
successor to an older drug.

Teva already sells the multiple
sclerosis drug Copaxone, which it
says is the most prescribed MS drug
in the world.

_____________
RACE TO CREATE
ORAL INSULIN
It is awfully tough to get effective
oral  delivery of a big, unwieldy
protein.

Acids and enzymes in the
gastrointestinal tract will chew up a
valuable therapeutic protein as
easily as they’ll tear into a bite of
steak.

An injection or IV drip may be
perfectly  reasonable for diseases
like cancer,  where drugs are
usually given in a hospital setting,
but for chronic  diseases like
diabetes or multiple  sclerosis,
which require daily or weekly
injections, a pill would be much
more  palatable.

Companies are especially keen to
develop alternative delivery
solutions  for insulin. Not only would
it represent  a major advance for
patients, but the  market for a
better-acting and easier-to-use
insulin would be gigantic—
insulin sales account for about $15
billion of the global diabetes market.

Attempts at inhaled insulin have
been  a colossal failure.

Here are some of the current
attempts  in clinical trials:

–India’s Biocon is developing IN-105,
an insulin molecule conjugated to a
short-chain polyethylene glycol
derivative. The technology was
originally developed at N.C.-based
Nobex, which Biocon bought in
2006.

–Ireland’s Merrion Pharmaceuticals
is  using technology acquired from
Elan  Corp. to enhance
gastrointestinal  permeation. In
2008, the company  began working
with Novo Nordisk on  solid oral
forms of insulin analogs; the  first
such analog was put into Phase I  
trials by Novo in late 2009.

–N.J.-based Emisphere Technologies
is working with Novo Nordisk on
GLP-1  analogs. In January 2011,
Novo started a  Phase I trial of the
first candidate using  Emisphere’s
Eligen technology.

–Israel’s Oramed is using capsules
with an enteric coating, which
controls  where in the intestinal
tract a pill is  absorbed. A Phase IIb
trial of ORMD-0801 conducted in
South Africa  showed the drug to be
safe and to  have a clinical impact
on insulin and  gluose levels.

–Dallas-based Access
Pharmaceuticals is using insulin-
containing nanoparticles coated with
vitamin B-12 analogs, which pull the
complex into circulation.

_______________________


OVERVIEW

OVERVIEW: ORGAN TRANSPLANT
INNOVATIONS


OVERVIEW: ADVANCES IN THE
TREATMENT OF
MRSA

OVERVIEW:  PANCREATIC CANCER
TREATMENT ADVANCES


FLU SEASON

HEPATITIS C:  TELAPREVIR VERSUS
BOCEPREVIR: A RACE TO BE THE
BEST

ANTIBIOTICS: THE GRAM NEGATIVE
BACTERIAL CHALLENGE

NEW MELANOMA DRUGS: HOPE
AND WORRY

ANEURYSM: THE SILENT KILLER

BREAST CANCER TREATMENT  
IMPROVEMENTS

LUNG CANCER TREATMENT HOPES

TARGETING CANCER STEM CELLS

AIRPORT SCANNERS RADIATION



___________
OPINION






COMPASSIONATE USE

What is expanded access?

For patients who cannot participate
in a clinical trial of an
investigational drug, but have a
serious disease or condition that
may benefit from treatment with the
drug, FDA regulations enable
manufacturers of such drugs to
provide those patients access to the
drug under certain situations,
known as "expanded access."

For example, the drug cannot
expose patients to unreasonable
risks given the severity of the
disease to be treated and the patient
does not have any other satisfactory
therapeutic options (e.g., an
approved drug that could be used to
treat the patient's disease or
condition). The manufacturer must
be willing to make the drug
available for expanded access use.
The primary intent of expanded
access is to provide treatment for a
patient's disease or condition, rather
than to collect data about the study
drug.

Expanded Access Studies can be
found by using the Advanced
Search feature at ClinicalTrials.gov.
Select "Search for Clinical Trials"
from the ClinicalTrials.gov
homepage, at http://ClinicalTrials.
gov .
Select "Advanced Search" on the
Search Page.
Find the field titled "Study Type"
and select "Expanded Access
Studies" from the pull-down menu
on the "Advanced Search" page.
Note: Additional search terms (e.g.,
condition) may be added to the
Advanced Search page.

A few important expanded access
trials that for the time being
(September 2011) are open for
applicants:

Carfilzomib Multiple Myeloma
Expanded Access Protocol for
Patients With Relapsed and
Refractory Disease
Condition:         Multiple Myeloma
Intervention:         Drug: Carfilzomib
Sponsor:         Onyx Pharmaceuticals

NCT ID:         NCT01410500
Call Center 1-866-518-4599

___________________

Expanded Access Program for
Aztreonam Lysine for Inhalation in
Canadian Patients With Cystic
Fibrosis
Conditions:         Cystic Fibrosis;   
Pseudomonas Aeruginosa
Intervention:         Drug: Aztreonam
lysine
Sponsor:         Gilead Sciences
Phase:         
NCT ID:         NCT00989807
Contact: Barbara Barrett         206-
832-2072         
barbara.barrett@gilead.com

_____________________

Use of TheraSphere For
Unresectable Hepatocellular
Carcinoma
Condition:         Liver Cancer
Intervention:         Device:
Theraspheres
Sponsors:         Stanford University;   
MDS Nordion
Phase:         
NCT ID:         NCT01076517
Start Date:         December 2008     
Contact: Shyam Panchal         (650)
725-9810         
spanchal@stanford.edu

______________________

Expanded Access Protocol (EAP)
Using the CliniMACS® Device for
Pediatric Haplocompatible Donor
Stem Cell Transplant
Conditions:         Acute
Lymphoblastic Leukemia;   Acute
Myeloid Leukemia;   Chronic Myeloid
Leukemia;   Myelodysplastic
Syndrome;   Lymphomas;   Bone
Marrow Failure;   
Hemoglobinopathy;   Immune
Deficiency;   Osteopetrosis;   
Cytopenias;   White Blood Cell
Abnormalities;   Red Blood Cell
Abnormalities
Intervention:         Biological: CD34+
enriched, T Cell Depleted donor
stem cell product
Sponsor:         University of
California, San Francisco
Phase:         
NCT ID:         NCT01200017
Start Date:         September 2010
Contact: Morton J. Cowan, MD         
415-476-2188         
mcowan@peds.ucsf.edu
Contact: Christopher Dvorak,
MD         415-476-2188         
DvorakC@peds.ucsf.edu

_________________

An Expanded Access Study of Oral
Liquid Efavirenz in the Treatment of
Children With HIV Infection
Condition:         HIV Infection
Intervention:         Drug: Efavirenz
Sponsor:         Bristol-Myers Squibb
Phase:         
NCT ID:         NCT00162227
Start Date:         September 2000
Contact: For participation
information at a USA site use a
phone number listed on  the
ClinicalTrials.gov homepage

___________________

Compassionate Use Trial for
Unresectable Melanoma With
Ipilimumab
Condition:         Melanoma
Intervention:         Drug: Ipilimumab
Sponsor:         Bristol-Myers Squibb
Phase:         
NCT ID:         NCT00495066
Call Center 1-866-518-4599

_____________________       

Expanded Access Protocol for PV-10
for Cutaneous or Subcutaneous
Tumors
Conditions:         Cutaneous or
Subcutaneous Tumors Where There
is no Comparable or Satisfactory;   
Approved Alternative Therapy
Intervention:         Drug: PV-10 (10%
rose bengal disodium)
Sponsor:         Provectus
Pharmaceuticals
Phase:         
NCT ID:         NCT01260779
Contact: Eric Wachter                 
wachter@pvct.com

_______________________

A Multicenter, Open-label Study of
CMX001 Treatment of Serious
Diseases or Conditions Caused by
dsDNA Viruses
Conditions:         Male or Female
Patients With a Serious or
Immediately Life-threatening;   
Disease or Condition Caused by
CMV, ADV, HSV, VAVC, VARV or;   
Monkeypox Viruses(s) Who Have a
Life Expectancy of ≥ 2 Weeks and
for;   Whom no Comparable or
Satisfactory Alternative Therapy is
Available
Intervention:         Drug: CMX001
Sponsor:         Chimerix
Phase:         
NCT ID:         NCT01143181
Contact: Herve Mommeja-Marin,
MD         919-806-1074         
hmommeja-marin@chimerix.inc

_______________________

VX-770 Expanded Access Program
Condition:         Cystic Fibrosis
Intervention:         Drug: VX-770
Sponsor:         Vertex
Pharmaceuticals Incorporated
Phase:         
NCT ID:         NCT01381289
Contact: VX-770 Expanded Access
Call Center         1-800-745-4484

_____________________
RECENT
UPDATES

FDA APPROVES
XTANDI FROM
MEDIVATION AND
ASTELLAS


OBESITY DRUG
BELVIQ APPROVED


GAUCHER DISEASE:
FDA APPROVES
ELELYSO



IMPOTENCE: FDA
APPROVES
STENDRA,
A NEW RIVAL TO
VIAGRA



PROSTATE CANCER:
HIFU PROSTATE
PROCEDURE SHOWS
LIMITED SIDE
EFFECTS



KIDNEY DIALYSIS:
THE FDA INITIATES 3
ARTIFICIAL KIDNEY
PROGRAMS



PSORIASIS: AMGEN'S
CANDIDATE IS
PROMISING IN PHASE
2



OBESITY DRUGS:
ARENA AND VIVUS
LOOKING TO FDA
APPROVAL LATER IN
2012



ANEMIC KIDNEY
PATIENTS: FDA
APPROVES A NEW
DRUG
OMONTYS


ORGAN
TRANSPLANTS:  STEM
CELLS LET
KIDNEY
TRANSPLANT
PATIENTS SKIP
REJECTION DRUGS



STROKE: FDA
APPROVES
COVIDIEN'S
SOLITAIRE DEVICE
FOR CLEARING
BLOOD CLOTS


ORGAN
TRANSPLANTS
INNOVATION: STEM
CELL INFUSION MAY
COMPENSATE FOR
REJECTION


FRENCH DRUG
PROCORALAN
RECEIVES EUROPEAN
APPROVAL FOR USE
IN HEART FAILURE


PANCREATIC
CANCER:DRUG
COMBO IS
PROMISING



DENTISTRY: WOMAN
RECEIVES
NEW JAW
MADE BY 3D
PPRINTER




DIABETES: AMYLIN'S  
DRUG
BYDUREON IS  
APPROVED


CYSTIC FIBROSIS:
FDA APPROVES
KALYDECO FROM
VERTEX



MULTIPLE
MYELOMA:FDA
APPROVES
VELCADE
SHOT


COLORECTAL
CANCER:
ZALTRAP
FROM REGENERON
AND SANOFI  IS
POTENTIALLY THE
FIRST NEW DRUG IN 5
YEARS




KIDNEY
CANCER:
INLYTA
FROM PFIZER SHOWS
STRONG PHASE 3
RESULTS


TRANSPLANTS, STEM
CELLS: FIRST US
PATIENT GETS STEM
CELL
TRACHEA
TRANSPLANT IN
EUROPE



BRAIN CANCER
VACCINE
ICT-107
TESTED IN PHASE 2


LIVER CANCER: LIVER
REMOVED,
RECONSTRUCTED,
REPLANTED



TELEMEDICINE
ROUNDUP AS OF
JANUARY 2012


BERLIN HEART: FDA
APPROVES THE FIRST
HEART PUMP FOR
CHILDREN



TENNIS ELBOW,
ACHILLES TENDON:
ULTRASOUND
GUIDED PROBE
CURES TENNIS
ELBOW IN 15 MINUTES


MYELOFIBROSIS:PRO
MISING RESULTS
FROM
YM BIO'S
MYELOFIBRIOSIS
DRUG: CYT387 IN  
MIDSTAGE TRIALS



LEUKEMIA:
PHARMACYCLICS
SHOWED STRONG
INTERIM RESULTS
FOR ITS LEUKEMIA
DRUG  PCI-32765





LEUKEMIA:
MICROMET'S
BLINATUMOMAB
PRODUCES HIGH
RATE OF DURABLE  
COMPLETE
REMISSIONS IN
PHASE 2 TRIAL



BREAST CANCER:
PERTUZUMAB FROM
ROCHE IS PROMISING
NEW BREAST
CANCER DRUG




PERIPHERAL
ARTERIAL DISEASE,
STEM
CELLS:
AASTROM
SHOWS GOOD
RESULTS IN PHASE 2
TRIAL



LIVER CANCER:
CELSION'S
PROMISING LIVER
CANCER DRUG IS  IN
PHASE 3 TRIAL



HEART STENTS: FDA
APROVES
PROMUS
STENT FROM
BOSTON SCIENTIFIC



ANEURYSMS: FDA
APPROVES APTUS
ENDOSTAPLING
SYSTEM TO REPAIR
FAILING  
AORTIC
ENDOGRAFTS


HEPATITIS C: THE
RACE FOR ORAL
HEPATITIS C DRUG IS
HEATING UP


LEUKEMIA: FDA
APPROVES ERWINAZE
TO TREAT A FORM OF
LEUKEMIA




WET
MACULAR
DEGENERATION OF
THE EYE: FDA
APPROVES
REGENERON EYE
DRUG EYLEA  



MYELOFIBROSIS:
FDA APPROVES
JAKAFI  THE FIRST
DRUG EVER FOR
MYELOFIBROSIS



ANEURYSM: FDA
APPROVES STENTS
TO REPAIR
ABDOMINAL
ANEURYSMS IN
PEOPLE WITH SMALL
ARTERIES

PROSTATE
CANCER:MEDIVATION'
S  
MDV3100 IS
SUCCESSFUL IN
PHASE 3 TRIAL


CYSTIC FIBROSIS:
VERTEX APPLIES FOR
FDA APPROVAL FOR
IVAFACTOR FOR
CYSTIC FIBROSIS


HEART: FDA
APPROVES EDWARD
LIFESCIENCE'S
HEART VALVE FOR US
MARKETS

STENTS: FDA
APPROVES ABOTT'S
XIENCE PRIME STENT
FOR US MARKETS


STENTS: FDA
APPROVES
MEDTRONIC'S STENT
FOR ILIAC ARTERIES



EXELITIS DRUG
CABOZANTINIB HELPS
WITH THYROID
CANCER


MULTIPLE
SCLEROSIS:  
BIOGEN'S
BG-12 IS A
PROMISING
COMPETITION TO
NOVARTIS'S GILENYA



HIV:
GILEAD'S QUAD
AND EVIPLERA


EPILEPSY: SURGERY
WORKS,  HALF OF
PATIENTS SEIZURE-
FREE FOR A DECADE


BRAIN INJURY: NEW
SUPERMACHINE TO
HELP
BRAIN INJURY
PATIENTS

ARTHRITIS:
VERTEX
HAS A PROMISING
DRUG TO TREAT
RHEUMATOID
ARTHRITIS



PROSTATE
CANCER:
ZYTIGA
(ABIRATERONE
ACETATE) ORAL PILLS
GO ON SALE IN THE
UK



BRAIN
CANCER:IMMUNOCEL
LULAR
THERAPEUTICS
ANNOUNCES 55%
OVERALL SURVIVAL
AT 3 YEARS FROM
PHASE 1 STUDY IN
GLIOBLASTOMA


BLOOD CLOTTING
PROMOTERS: FDA
APPROVES GEL TO
STOP BLOOD FLOW
DURING BLOOD
VESSEL SURGERY


LUNG
CANCER:SMOKERS
QUIT WITH CHEAP
REMEDY



HODGKIN'S
LYMPOMA:  FDA
APPROVES NEW
LYMPHOMA DRUG,
ADCETRIS



LYME DISEASE: NEW
ANTIBIOTIC
OINTMENT MAY
PREVENT LYME
DISEASE FROM TICK
BITES



ALZHEIMER'S:INHALAT
ION OF INSULIN
APPEARS TO SLOW
DOWN ALZHEIMER'S


PROSTATE
CANCER:
ALPHARADIN
FROM BAYER: PHASE
3 TRIAL STOPPED
FOR EFFICIENCY


LUNG CANCER: FDA
APPROVES
XALKORI
(CRIZOTINIB) FOR A
TYPE OF LATE STAGE
LUNG CANCER


RUXOLITINIB FROM
INCYTE IS
PROMISING DRUG
FOR MYELOFIBROSIS
SUFFERERS


MELANOMA: FDA
APPROVES
ZELBORAF FROM
ROCHE


GOUT:  
KRYSTEXXA
FROM SAVIENT
PHARMA  IS HELPFUL
FOR SEVERE GOUT
SUFFERERS


RHEUMATOID
ARTHRITIS: PFIZER'S
TOFACITINIB IS
EFFECTIVE IN  PHASE
3 TRIAL




LEUKEMIA: HUGE
RESULTS FROM A
SMALL TRIAL RAISE
HOPE FOR
BREAKTHROUGH IN
CANCER TREATMENT




FDA APPROVES RX
HERCULINK FOR
KIDNEY STENTING IN
THE US



INCIVEK, A NEW
HEPATITIS C DRUG
SHOWS STRONG
SALES


SILVER ALLOY
URINARY CATHETERS
REDUCE
URINARY
TRACT INFECTIONS



DANGER: FAKE
MEDICINES
PURCHASED BY
AMERICANS FOR
SERIOUS ILLNESSES


AVI-4658 IS
PROMISING DRUG
FOR MUSCULAR
DYSTROPHY


FDA APPROVES
BRILINTA, A NEW
BLOOD THINNER
FROM ASTRAZENECA



A SIMPLE FILTER
COULD CUT THE HIGH
RISK OF
STROKE
DURING THE TAVI
PROCEDURE


HEART:
TAVI
(TRANSCATHETER
AORTIC-VALVE
IMPLANTATION) TRIAL
SHOWS GOOD
RESULTS



WRIST ANGIOPLASTY:
THE CATHETER IS
PULLED THROUGH
THE WRIST INSTEAD
OF THE GROIN


VETERINARY:VACCINE
S TO HELP
SHRIMP
FARMERS




BIODEFENSE:
VACCINE ST-246 MAY
END THE THREAT OF
SMALL POX



TRUVADA: TAKING
DAILY PILL GREATLY
REDUCES THE RISK
OF ACQUIRING HIV



PLANNED  
IMPROVEMENTS  FOR
ARTHRITIS DRUG
HUMIRA TO MEET
COMPETITION



FIRST EVER
DOUBLE
LEG TRANSPLANT IN
SPAIN


ANTIBIOTIC
RESISTANT
GONORRHEA FOUND
IN JAPAN


STEM CELL THERAPY
PROVIDES RELIEF
FOR TRIAL PATIENTS
WITH UNTREATABLE
CHEST PAIN



AFINITOR BY
NOVARTIS HELPS
SHRANK
BENIGN
BRAIN TUMORS


AFINITOR BY
NOVARTIS IS A
PROMISING DRUG
FOR BREAST CANCER




OBESITY:
CHINESE
FOOD MAY BE MORE
FATTENING THAN
MCDONALDS



CANCER PATIENT
SAVED WITH
LAB-MADE
WINDPIPE



WEIGHT- LOSS  
SURGERY CURES
MANY OBESE
PEOPLE OF THEIR
DIABETES


COCAINE LACED WITH
VETERINARY DRUG
LEVAMISOLE EATS
AWAY AT FLESH


A STRICT DIET CAN
REVERSE
TYPE 2
DIABETES


LAVIV, A NEW
INJECTIBLE WRINKLE
TREATMENT TO
COMPETE WITH
BOTOX


NOVARTIS'S  
GILENYA
  FOR MULTIPLE
SCLEROSIS


FOR ATRIAL
FIBRILLATION
CATHETER ABLATION
PROCEDURE AVOIDS
DRUGS AND SURGERY


BELATACEPT  
APPROVED  FOR
PREVENTING GRAFT
REJECTION


POTIGA  TABLETS
APPROVED FOR
EPILEPSY


CHANGING
TREATMENT TO
FIGHT
E COLI


ROCHE'S
VEMURAFENIB FOR
MELANOMA
TREATMENT PLAYS A
STARRING ROLE AT
ASCO (American
Society of Clinical
Oncology)  IN 2011



HORMONE BLOCKING
DRUG REDUCES
BREAST CANCER RISK


DIFICID, A NEW
MEDICINE  BY
OPTIMER,  IS
APPROVED BY FDA  
AGAINST
C. DIFFICILE



BAD NEWS: NIASPAN
TRIAL, AIMING TO
INCREASE  GOOD
CHOLESTEROL IN
PATIENTS,   FAILS


NOVARTIS HAS
PROMISING
NEW
DRUG FOR GOUT


TELOVAC  VACCINE
TRIAL IN PHASE 3
WITH HIGH PROMISES
FOR PANCREATIC
CANCER


FDA APPROVES FIRST
MICROINJECTION
FLU VACCINE


TELEMEDICINE:
WORKING EXAMPLES
FROM  DENMARK


FDA APPROVES
ZYTIGA FOR
PROSTATE CANCER


$50 EYE DRUG EQUAL
TO  $2,000 DOSE

TRANSPLANT
ORGANS TO BE FIXED
BEFORE
TRANSPLANTATION



CATHERINE
ZETA-JONES IS
TREATED FOR
BIPOLAR II DISORDER



TELEMEDICINE:
STUDENT PROJECT
USE SMARTPHONE
CAMERA TO
DIAGNOSE MALARIA


SYNTHETIC DRUGS:
TEN TIMES WORSE
THAN COCAINE


USING A
PROGESTERONE GEL
WILL CUT THE RISK
OF PREMATURE
BIRTH


SCIENTISTS GROW
RETINA IN TEST TUBE
FOR THE FIRST TIME


MERCK'S GARDASIL
VACCINE  NOT
APPROVED FOR
OLDER WOMEN


GROW YOUR OWN
HEART


HOSPITAL TEXTILES
TO KILL MRSA
SUPERBUG


DIABETES DRUG
ACTOS REDUCES THE
RISK OF DEVELOPING
THE DISEASE



BEATING HEART
TRANSPLANTS USING  
TRANSMEDICS
ORGAN BOX



EPILEPSY:  
KETOGENIC DIET
REDUCES NUMBER
OF SEIZURES IN
DRUG RESISTANT
CHILDREN



REGENERON EYE
DRUG SHOWS
PROMISE FOR  WET
MACULAR
DEGENERATION



STEM CELLS FROM
BELLY FAT MAY BE A
TREATMENT FOR
HEART ATTACK



KIDNEY PROCEDURE
REDUCES HIGH
BLOOD PRESSURE


MERCK'S NEW DRUG
RAISES GOOD
CHOLESTEROL


STEM CELLS
INJECTED INTO THE
BRAIN OF A STROKE
PATIENT


CRIZOTINIB:
RESPONSE RATE
UNPRECENDENTED IN
LUNG CANCER STUDY


CONTRACEPTIVE GEL
COULD REPLACE
BIRTH CONTROL PILL

BOTOX HAS BEEN
APPROVED FOR
TREATMENT OF
MIGRAINE BY THE
FDA AND LICENSED IN
THE UK


HERCEPTIN TEST
APPROVED FOR
STOMACH CANCER


SURGEONS
IMPLANTED STENT
INSIDE THE SKULL OF
A 14 YEAR OLD BOY

BLOOD THINNER
PRADAXA APPROVED
BY FDA


HEART MONITORING
VIA MOBILE PHONE


AMG386 FROM
AMGEN  SHOWS
ANTITUMOR ACTIVITY
AGAINST OVARIAN
CANCER


NEW  DRUG  FOR
CHRONIC KIDNEY
DISEASE IMPROVES
KIDNEY FUNCTION


MEDICATIONS THAT
MAY CAUSE
MEMORY LOSS


3F8 ANTIBODY
FIGHTS EFFECTIVELY
NEUROBLASTOMA


IUD PROPOSED TO
TREAT UTERINE
CANCER

PLURISTEM STEM
CELL THERAPY
WORKS WELL FOR
PERIPHERAL
ARTERIAL DISEASE


MIROCOCEPT COULD
DOUBLE LIFE OF
TRANSPLANT ORGANS


ACNE:  SOME
LOW-TECH
SOLUTIONS   FOR
ACNE  FROM THE UK


VITAMIN
SUPPLEMENT DHEA
HELPS WOMEN TO
GET PREGNANT


ANTI-AGING: T-65  
THE FIRST COMPUND
TO POTENTIALLY
EXTEND HUMAN LIFE


TWO NEW FAT
REDUCING DEVICES
APPROVED BY THE
FDA


NEW TEST FOR  
DRUG-RESISTANT TB
GIVES RESULTS IN
HOURS NOT WEEKS

INDIAN DOCTOR:
KEYHOLE SURGERY
CAN CURE DIABETES

MEDTRONIC'S   
"SLINKY" STENT
IMPLANTED IN
EUROPE

DR DENISE
FAUSTMAN: TO STOP
DIABETES SHE'S  
ATTACKING THE
IMMUNE SYSTEM


MAGIC MUSHROOMS
INGREDIENT
BENEFICIAL TO
CANCER PATIENTS


PHOTOCHEMICAL
TISSUE BONDING TO
REPAIR WOUNDS
WITH LIGHT

PROMISING NEW
DRUGS FOR
UPCOMING  H1N1
SEASONS

BIOSYNTHETIC
CORNEA  CURED THE
BLIND

VALVE REPLACEMENT
FOR A 101 YEAR OLD
WOMAN

MAMMOGRAPHY:
BREAST PEM
IMAGING COMPARED
TO MRI

VACCINE FOR
SHINGLES TESTED IN
PHASE 3


PROMISING: PLX4032,
A BRAF INHIBITOR
FOR MELANOMA
TREATMENT

FOR MELANOMA, first
in its class,
ipilimumab showed
68% increase in
survival.

SURGERY MAY
REDUCE DIABETICS'
NEED FOR DRUGS

LUBRICANTS USED IN
ANAL SEX MAY MAKE
IT EASIER FOR HIV TO
BE TRANSMITTED

NASAL COOLING OF
THE BRAIN

BOTOX TO CLEAR UP
ACNE

NEXAGON:  A NEW
GEL FOR LEG ULCER


PLANT BASED H1N1
VACCINE
PRODUCTION


GUT INFECTION:  
FECAL
BACTERIOTHERAPY


LEUKEMIA:  
TAMIBAROTENE
ERADICATES EX-NBA
PLAYER'S LEUKEMIA


DENTISTRY:  A GEL
TO REPLACE FILLING
WORK


BIOHEART  TESTING
STEM CELLS IN
CONGESTIVE HEART
FAILURE

WINDPIPE
TRANSPLANTS USING
STEM CELLS

PROGESTERONE  
GIVEN WITHIN 4
HOURS FROM
INJURY TESTED


DR ZAMBONI'S
PIONEERING THEORY
REGARDING
MULTIPLE SCLEROSIS


DARPA'S THOUGHT
CONTROLLED
PROSTHETIC ARM


NOVOCURE'S
NOVOTTF DEVICE
FOR  RECURRENT
GLIOBLASTOMA


DELCATH DELIVERY
OF CANCER DRUG BY
CATHETER  FOR
MELANOMA


CARTILAGE REPAIR
BY CULTURING CELLS


GLYSENS
IMPLANTABLE
GLUCOSE MONITOR
FOR DIABETICS


TCA CELLULAR
THERAPY INFUSES
ADULT STEM CELLS
AFTER BYPASS


NEW DRUGS:
SPRYCEL AND
TASIGNA  IN
LEUKEMIA
TREATMENT


THE DRUG REOLYSIN
TESTED FOR
MULTIPLE CANCERS



U MICHIGAN
DEVELOPS
INHALABLE DRUG
AGAINST CYSTIC
FIBROSIS


PROLIA APPROVED
FOR OSTEOPOROSIS,
TESTED FOR CANCER


THORACAB:  BYPASS
WITHOUT CUTTING
THROUGH THE
BREASTBONE


STENTING  TO CURE
IMPOTENCE


IMPOTENCE:  
INHALER TO HELP
MEN GET AN
ERECTION IN A HURRY


NEW MEMOKATH
STENT FOR KIDNEY
STENTING


STENTING TO CURE
FLAT FOOT


TOMATO EXTRACT  
TO REDUCE
CHOLESTEROL


SPINE: LUMBAR
FUSION WITH STEM
CELLS


CREAM FROM
BREAST MILK TO
CLEAR UP ACNE


STROKE
DRUGS:APIXABAN
TRIAL STOPPED FOR
A REASON OF
WORKING TOO WELL


STEM CELL THERAPY
SHRINKS ENLARGED
HEARTS


LUNG CANCER:
ARTIFICIAL AIRWAY IS
A WORLD FIRST


GOUT: REGENERON
PHARMA HAS
PROMISING THERAPY
IN PHASE 3


AUTISM:ROUNDWORM
S SUPPLIED BY A
GERMAN COMPANY  
ELIMINATE VIOLENT
BEHAVIOUR IN
AUTISTIC CHILD

VERTEX REPORTS
SUCCESS WITH NEW
DRUG FOR CYSTIC
FIBROSIS

HIGH FAT CONTENT,
NOT CHOLESTEROL
TO BLAME FOR
STROKE


BREAST
RECONSTRUCTION
FROM STEM CELLS
AND BODY'S OWN FAT


PV-10 IS PROMISING
THERAPY FOR
METASTATIC
MELANOMA

FECAL
BACTERIOTHERAPY
TO CURE  PATIENTS
WITH C DIFFICILE


FOR ATRIAL
FIBRILLATION
MEDTRONIC DEVICE
IS APPROVED BY FDA


LUNG IMPLANT: A
STEP TOWARD  
ARTIFICIAL LUNG


XGEVA  FROM
AMGEN SHOWS
STRONG SALES
POTENTIAL
FOR PROSTATE
CANCER

FDA SAYS STOP
USING  DIETARY
SUPPLEMENTS  FOR
SEXUAL
ENHANCEMENT



PROMISING NEW
DRUG FOR
HODGKIN'S
LYMPHOMA



ZEBINIX  IS AN
ADD-ON TREATMENT
FOR PARTIAL ONSET
SEIZURES OF
EPILEPSY

3D MAMMOGRAPHY
OFFERS MORE
ACCURATE
SCREENING FOR
BREAST CANCER

MERCK'S GARDASIL
PREVENTS HPV
INFECTION, GENITAL
WARDS IN MEN


AROMASIN: A
HORMONE BLOCKING
DRUG REDUCES
BREAST CANCER RISK


MICROMET'S
BLINATUMOMAB IS
PROMISING DRUG
FOR LEUKEMIA


YERVOY  BY
BRISTOL-MYERS
SQUIBB FOR
MELANOMA

LILLY'S
ALIMTA FOR
NON-SMALL CELL
LUNG CANCER

CABOZANTINIB FROM
EXELIXIS  FOR
PROSTATE CANCER

AMGEN'S
AMG102
FOR COLON CANCER

ROCHE'S
METMAB
FOR LUNG CANCER

GDC-0449:
PROMISING DRUG
FOR SKIN CANCER

PONATINIB  IS
PROMISING DRUG
FOR LEUKEMIA

T-DM1 IS PROMISING
DRUG FOR BREAST
CANCER



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EMERGING  LUNG CANCER
DRUGS: A TREND TOWARD
PERSONALIZED  TREATMENT

Sales of Genentech/OSI
Pharmaceuticals/Roche/Chugai
Pharmaceutical's Tarceva and Eli
Lilly's Alimta, two branded
treatments that dominated the non-
small-cell lung (NSCLC) cancer
market in 2010, may weaken after
2015.

In the future testing for mutated
genes becomes more important.
As a result, many of the emerging
therapies for non-small-cell lung
cancer will increasingly provide
patients with a personalized
approach to treatment.


Previous studies suggest that
NSCLC patients with EGFR-mutated
tumors respond well to EGFR
inhibitors such as Tarceva or
AstraZeneca's Iressa. However,
patients with EGFR T790M
mutations and mutations in the
KRAS gene downstream of the
EGFR pathway are more likely to
develop resistance to EGFR
inhibitors. Testing for these
mutation types in NSCLC could
help oncologists decide whether
to treat patients with an EGFR-
inhibiting agent or an irreversible
pan-HER inhibitor, such as
dacomitinib.



In August 2011 Pfizer's Xalkori
(crizotinib) won FDA approval  for
treatment of some patients with
late non-small cell lung cancer
(NSCLC) who have a genetic
mutation which can fuel the growth
of cancerous cells. The agency
simultaneously approved a test for
the mutated gene, known as an
abnormal anaplastic lymphoma
kinase gene (ALK), from Abbott
Molecular Diagnostics. Around one
out of every seven NSCLC patients
have the gene.


In the next 10 years  several more
targeted treatments for small
patient subsets to enter the non-
small-cell lung cancer market.The
important candidates are as
follows.


BOEHRINGER INGELHEIMS'S
TOMTOVOK/AFATINIB
In October 2010 a new Boehringer
Ingelheim Phase III trial called "Lux-
Lung 5" began with this drug.

Afatinib is a next generation
tyrosine kinase inhibitor that
inhibits human epidermal growth
factor receptor 2 (Her2) and
epidermal growth factor receptor
(EGFR) kinases. Afatinib is not only
active against EGFR mutations
targeted by first generation TKIs
like erlotinib (Tarceva) or gefitinib
(Iressa), but also against those not
sensitive to these standard
therapies.

It is also undergoing Phase II trials
for breast, prostate, and head and
neck cancers, as well as glioma.

PFIZER'S DACOMINITIB
The KRAS test that Pfizer is using
for dacomitinib is also based on
Qiagen's PCR-based therascreen
KRAS RGQ kit. This is the same
platform upon which the company
has built KRAS companion tests for
two colorectal drugs, Amgen's
Vectibix and Bristol-Myers
Squibb's Erbitux.
Qiagen estimates that there are
more than 1.5 million NSCLC cases
reported each year globally. It is
estimated that between 10 percent
and 20 percent of NSCLC patients
have KRAS mutations.

If Pfizer can show that dacomitinib
is not only more effective than
currently marketed EGFR
inhibitors in advanced lung cancer
patients, but is specifically
superior to such drugs in a
molecularly defined subset of
refractory NSCLC patients, then
that would be a way to carve out a
specific market for the newer drug.



GENENTECH/ROCHE/CHUGAI'S
ONARTUZUMAB/METMAB
This is a  humanized monoclonal
antibody directed against the
hepatocyte growth factor receptor
(c-Met) with potential
antineoplastic activity.
Onartuzumab binds to the
extracellular domain of c-Met,
preventing the binding of its
ligand, hepatocyte growth factor
(HGF); the activation of the c-Met
signaling pathway is thus inhibited,
which may result in cell death in c-
Met-expressing tumor cells. c-Met,
a receptor tyrosine kinase, is
overexpressed on the cell
surfaces of a variety of cancer cell
types and may play a key role in
their proliferation, invasion and
survival.



ARQULE/DAIICHI SANKYO/KYOWA
HAKKO KIRIN'S TIVANTINIB
In March 2011 Daiichi Sankyo has
begun enrolling patients in Europe
into a large, multinational phase III
trial of tivantinib (ARQ 197).
Tivantinib is an investigational
small molecule inhibitor of the c-
MET receptor tyrosine kinase in
final phase of clinical development
for the treatment of advanced, non-
squamous, non-small cell lung
cancer (NSCLC).




THE FAILURE OF SOME PARP
INHIBITOR TRIALS
In early 2011, one of the most
exciting classes of compounds in
oncology at that time—inhibitors of
the DNA repair enzyme poly-(ADP
ribose) polymerase (PARP)—
suffered a double blow.

In January 2011, Paris-based
Sanofi-Aventis announced that
iniparib, the most advanced PARP
inhibitor at the time in trials, failed
to prolong survival in its first
phase 3 trial in metastatic, triple-
negative breast cancer despite
promising phase 2 trial results.
Then, the following month, London-
based AstraZeneca said that it
would not, as it had previously
planned, pursue phase 3
development of its PARP inhibitor
olaparib  in hereditary BRCA1- and
BRCA 2-associated breast cancer—
considered one of its strongest
indications.


At this point not all hope is lost.
The concept seems valid:  by
inhibiting PARP, the drugs make
tumor cells more sensitive to
chemotherapy because the PARP
protein is involved in removing
chemotherapy-induced platinum
damage from DNA. Without the
repair mechanism, the tumor cell is
more likely to die.

Abbott Labs has a PARP inhibitor
called veliparib, as does Pfizer .
And Teva Pharmaceuticals has one
as well through its purchase of the
company Cephalon.



UNMET NEEDS OF PATIENTS
Even as non-small-cell lung cancer
treatments become more specific
to particular histological and
molecular subtypes, few
treatments in advanced clinical
development will address the high
level of unmet needs of patients
with squamous cell tumors, which
represent approximately 30 to 40
percent of the total population,
and KRAS mutations, which
represent 22 percent of patients
with adenocarcinomas.  These are
sizeable and potentially
commercially lucrative
underserved patient populations.

_______________

HEART ATTACKS: NEWER
MEDICATIONS

Acute coronary syndrome,
or ACS, includes heart
attacks and chest pain and
results in 1.2 million
hospitalizations a year in
the US.


Even with good care,
patients hospitalized for
ACS remain at high risk of
having a subsequent heart
attack or stroke.


While doctors have been
attempting to come up with
better blood thinners for
heart patients for years, it
has been tricky to do this
without causing too much
bleeding.

In November 2011 US
company  Johnson&
Johnson and its German
partner, Bayer, said they
plan by year's end to seek
Xarelto's approval for
treating acute coronary
syndrome. Xarelto has  
already been approved for
atrial fibrillation.  

ACS treatment is a 1 billion
dollar market.

If cleared for ACS, Xarelto
would enter a market that
includes Brilinta from
London-based AstraZeneca
Plc  (FDA approved in July
2011), and Effient from
Indianapolis-based Eli Lilly
& Co. These drugs are used
instead of the standard
treatment, Plavix, a drug
made by New York-based
Bristol-Myers Squibb Co.
and Paris-based Sanofi.

Xarelto would likely be
used in concert with Plavix.

In its new study of 15,526
patients, J&J and Bayer
narrowly succeeded in
finding a dose that was
effective at preventing
heart attacks and heart
deaths without
unacceptable bleeding.

Overall, the drug reduced
heart attacks, strokes, and
cardiovascular deaths by 16
percent. The reduction in
deaths was only seen in the
lower of two doses tested.

Drugs already marketed for
ACS, including Brilinta,
Effient and Plavix, block
cell fragments in the blood
called platelets from
sticking together. Xarelto,
by contrast, blocks a
second process involved in
clotting, an enzyme
involved in producing fibers
that help the blood
coagulate.

Pradaxa from German
drugmaker Boehringer
Ingelheim GmbH and
Eliquis from New York-
based Pfizer Inc. and Bristol-
Myers Squibb Co. are from
the same family of
medicines. Until recently, it
wasn't clear this class
would be a competitor in
ACS patients. Eliquis a year
ago failed to prevent heart
attacks and cardiac deaths
in a study while causing
more major bleeding.

All three treatments are
attempting to replace
standard use of warfarin, a
more than 50-year-old
medicine that is a form of
rat poison.

One reason why the Xarelto
study may have worked is
that it used a low dose to
minimize bleeding, only
one-half to one- quarter of
the Xarelto dose used to
treat atrial fibrillation.

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