Prostate cancer drugs:

Prostate cancer is cancer that starts in
the prostate gland. The prostate is a
small, walnut-sized structure that
makes up part of a man's reproductive
system. It wraps around the urethra,
the tube that carries urine out of the
body.

Currently, the world's top selling
prostate cancer drugs are Taxotere
(docetaxel), a chemotherapy sold by
Sanofi , and drugs that reduce
testosterone, the male hormone that
fuels the growth of prostate cancer.
They also include AstraZeneca Plc's
Zoladex and Casodex, and widely-used
Lupron.




FDA APPROVES XTANDI FROM
MEDIVATION AND ASTELLAS

The U.S. Food and Drug
Administration in August 2012  
approved Xtandi (enzalutamide)  from
Medivation and Astellas Pharma to
treat men with late-stage (metastatic)
castration-resistant prostate cancer
that has spread or recurred, even with
medical or surgical therapy to minimize
testosterone.

Approved for prostate cancer patients
previously treated with docetaxel,
another anti-cancer treatment, Xtandi
was reviewed under the FDA's priority
review program. The program provides
for an expedited six-month review for
drugs that may offer major advances in
treatment or that provide a treatment
when no adequate therapy exists.
Xtandi received FDA approval three
months ahead of the product's
prescription drug user fee goal date of
Nov. 22, 2012.

Prostate cancer forms in a gland in the
male reproductive system found below
the bladder and in front of the rectum.
The male sex hormone testosterone
stimulates the prostate tumors to grow.
According to the National Cancer
Institute, an estimated 241,740 men
will be diagnosed with prostate cancer
and 28,170 will die from the disease in
2012.


FDA APPROVES ZYTIGA FOR
PROSTATE CANCER
In April 2011 the U.S. Food and Drug
Administration approved Zytiga in
combination with prednisone to treat
patients with a certain type of late-
stage prostate cancer in patients who
have been previously treated with
chemotherapy.

Zytiga, made by Centocor Ortho
Biotech, a unit of Johnson & Johnson ,
is a pill that targets a protein called
cytochrome P450 17A1 (CYP17A1),
which plays an important role in the
production of testosterone. The drug
works by decreasing the production of
this hormone that would stimulate
cancer cells to continue growing.

In prostate cancer, the male sex
hormone testosterone stimulates
prostate tumors to grow. Drugs or
surgery are used to reduce
testosterone production or to block
testosterone's effects. However,
sometimes prostate cancer can
continue to grow even when
testosterone levels are low. Men with
these cancers are said to have
castration-resistant prostate cancer,
which is the type of cancer Zytiga was
approved to treat.

The company said Zytiga would cost
about $5,000 per month. A typical
course of therapy is about eight
months.



ZYTIGA (ABIRATERONE ACETATE)
ORAL PILLS GO ON SALE IN THE UK
The once-daily pill officially launched in
the UK in September 2011 after the
European Commission  approved it for
the treatment of metastatic prostate
cancer. Abiraterone acetate was
licensed for use in combination with
the steroids prednisone or
prednisolone, by men whose disease
has developed resistance to
conventional hormone therapies and
docetaxel-based chemotherapy.

The pill is marketed by Janssen (a
Johnson & Johnson company) under
the trade name ZYTIGA. It  has been
shown in clinical trials to prolong
survival for men with advanced
prostate cancer.

An estimated 10,500 men in the UK
have advanced prostate cancer that
has become resistant to standard
hormone treatments.

Abiraterone acetate is a new type of
treatment for prostate cancer that
works by blocking the synthesis of
testosterone in all tissues including the
tumor itself, not just the testes. This
testosterone would otherwise continue
to fuel prostate cancer growth and
spread.

Abiraterone was discovered at the ICR
in what is now the Cancer Research
UK Cancer Therapeutics Unit and
further developed at the ICR and The
Royal Marsden Hosptal.

Abiraterone is taking the market by
storm; there is a much faster effect
with it than with Dendreon's Provenge.
Patients feel they're getting something
beneficial. Pain is markedly improved,
along with the ability to eat, drink, go
out and do what they normally would
do.

A patient says, 'Look, I really don't see
the need to sit here and send my
(blood) to wherever. I really don't want
to wait. I want to take a pill and go to
Florida.' "

While Zytiga is expensive -- at about
$5,000 a month, usually for eight
cycles -- it is far less costly than
Provenge.



MEDIVATION'S  MDV3100 IS
SUCCESSFUL IN PHASE 3 TRIAL
In January 2012 it was reported that
the phase III study  men treated with
MDV3100, a pill, reported a median
survival of 18.4 months compared to
13.6 months for men treated with a
placebo -- or a 4.8-month survival
benefit favoring MDV3100.

Analyzed another way, the risk of a
man dying of prostate cancer while
being treated with MDV3100 was
reduced by 37%. The results from the
interim analysis were statistically
significant, which is why the study was
stopped early.

The results came from an interim
analysis of a late-stage trial of the
drug, MDV3100, in men who had
previously received chemotherapy.
The benefit was strong enough to stop
the 1,200-patient study early and
switch men who had taken the placebo
over to MDV3100.

The estimated median overall survival
in men who had received MDV3100
was about 18.4 months, compared with
13.6 months for the placebo group, for
a 37% reduction in risk of death, the
companies said.

MDV3100 is the first in a new class of
medicines called androgen receptor
signaling inhibitors, and is an oral,
once-daily drug. The company is
running a separate study of the drug in
men who haven't undergone
chemotherapy.

If it comes to market, it would mark the
latest in a series of new therapies for
prostate cancer, including products
from Dendreon Corp. and Johnson &
Johnson.

J&J's Zytiga also is a hormonal-related
treatment for prostate cancer, and is
approved for use in men who have
already undergone chemotherapy.

In June 2011 Medivation, Inc.  and
Astellas Pharma Inc.  presented
preliminary data on their prostate
cancer candidate, MDV3100, from an
ongoing study.

Preliminary results confirmed the anti-
tumor effects and tolerability profile of
MDV3100 as seen in earlier phase I/II
studies. The 160 mg daily dose of
MDV3100 is being evaluated.

The study is being conducted with 58
heavily pre-treated advanced prostate
cancer patients.

Results showed that 45% of the 55
evaluable patients enrolled in the
study experienced at least a 50%
reduction in prostate-specific antigen
(PSA) levels. The bone marrow biopsy
data showed that MDV3100 was
associated with decreased levels of
androgen receptor in the cell nucleus
where it can promote cancer growth.

MDV3100 was found to be generally
well tolerated with fatigue being the
most common adverse event.

Medivation has an agreement with
Japanese company, Astellas Pharma,
for the development and
commercialization of MDV3100.

An open-label, single-arm study (n=60)
is being conducted in Europe.
MDV3100 is currently in another phase
II (head-to-head) study (TERRAIN),
which is comparing MDV3100 with
AstraZeneca’s  Casodex (bicalutamide).

MDV-3100 is now seen as a rival for
Johnson & Johnson’s Zytiga, Dendreon’
s Provenge, and Exelixis’ cabozantinib.




NEW VACCINE PROSTVAC IS TESTED
In clinical trials  an experimental
vaccine is tested to treat prostate
cancer that could be taken out of the
freezer and injected into patients --
eliminating the hassles seen with
Provenge.

The National Cancer Institute
developed the vaccine, called
ProstVac, and licensed it to Danish
biotechnology company Bavarian
Nordic . NCI would be entitled to
royalties on sales of the vaccine, which
is slated to move into late-stage trials
in late  2011.

ProstVac prolonged patient lives by
eight months in mid-stage trials --
roughly twice the benefit seen in
separate trials of Provenge and Zytiga.
But  ProstVac's true potential will not
be known until its far-larger planned
Phase III trials are completed.

The vaccine coaxes immune system T-
cells to attack a protein called Prostate-
Specific Antigen (PSA) -- could prove
to be a bigger drug than Provenge.

Here's why: because it is off the shelf.
There are no logistical constraints.




ALPHARADIN FROM BAYER FOR
PROSTATE CANCER: TRIAL
STOPPED FOR EFFICIENCY
In June 2011, Algeta and Bayer
Pharma AG announced that the phase
III trial evaluating Alpharadin (radium-
233 chloride) for treating symptomatic
bone metastases in  patients met its
primary endpoint by significantly
improving overall survival. The trial
was stopped early based on this
positive result and a recommendation
from the Independent Data Monitoring
Committee.

Radium-223 chloride is being
developed by Algeta (a Norwegian
company) with Bayer Pharma AG
(formerly Bayer Schering Pharma AG).

The development of bone metastases
represents a serious development for
cancer patients as they are associated
with a dramatic decline in patient
health and quality of life, ultimately
leading to death.

Bone metastases represent a major
unmet medical need, occurring
frequently in certain late-stage
cancers, e.g. prostate (in up to 90%
patients), breast (up to 60 %) and lung
(up to 40%).



CABOZANTINIB FROM EXELIXIS IS
PROMISING FOR PROSTATE CANCER
Perhaps a drug referred to as "cabo"
deserves to have its day in sun.
Indeed, there are plenty of folks at
Exelixis  who are hoping that XL184
(cabozantinib) shines in clinical trials;
it's the most advanced candidate in the
South San Francisco-based drug
developer's pipeline.

Exelixis says that the drug---which at
the same time inhibits two molecular
drivers of tumor growth, vascular
endothelial growth factor (VEGF)
receptor 2 and MET---is the most
advanced treatment that targets MET.

In February 2011, the company said
that a Phase II trial of the drug
involving patients with prostate cancer
that had spread to other organs was
showing promise. For 62 men whose
cancer had spread into their bones
and could be evaluated with bone
scans, the drug showed it had at least
stabilized the cancer in all but one of
them.

The drug is now in six clinical trials,
including a Phase III trial involving
adults with medullary thyroid cancer.

The company has been riding solo with
"cabo" since Bristol-Myers Squibb  
handed back rights to it in June 2010
after the two companies couldn't see
eye-to-eye on plans to develop the
drug. Exelixis CEO Michael Morrissey
might get the last laugh if the drug
performs as well as he hopes.

At ASCO, the company  showed more
results in prostate cancer patients,
both in terms of bone scans and more
traditional endpoints such as soft
tissue responses and progression free
survival.

Despite the sensational results earlier
this year, it is still unclear what the
clinical relevance of bone scan
resolution is. For example, some argue
that bone scans provide indirect
evidence to the presence of bone
metastases and as such are not
reliable. Exelixis is expected to present
cabozantinib's anti-bone mets effect,
assessed by other means such as MRI
or biopsy.



XGEVA (PROLIA) FROM AMGEN
SHOWS STRONG SALES POTENTIAL
FOR PROSTATE CANCER
The drug was approved in November
2010 for preventing cancer-related
bone injury.

The U.S. Food and Drug
Administration approved Xgeva
(denosumab)  to help prevent skeletal-
related events (SREs) in patients with
cancer that has spread (metastasized)
and damaged the bone. Skeletal-
related events include bone fractures
from cancer and bone pain requiring
radiation.

Xgeva is a monoclonal antibody that
targets a protein involved in cancer-
related bone destruction called human
RANKL. Other FDA-approved drugs
for similar conditions include Zometa
(zoledronic acid) and Aredia
(pamidronate disodium).

Xgeva is not approved for patients with
multiple myeloma or other cancers of
the blood.

Xgeva has a different mechanism of
action than currently approved drugs
aimed at reducing bone complications
from cancer.

Xgeva’s safety and effectiveness were
confirmed in three randomized, double-
blind clinical studies in 5,723 patients
comparing Xgeva with Zometa. One
study involved patients with breast
cancer, another in patients with
prostate cancer, and a third included
patients with a variety of other cancers.

The studies were designed to measure
the time until occurrence of a fracture
or spinal cord compression due to
cancer or until radiation or surgery for
control of bone pain was needed.

In patients with breast or prostate
cancers, Xgeva was superior to
Zometa in delaying SREs. In men with
prostate cancer, the median time to an
SRE was 21 months with Xgeva
compared to 17 months with Zometa.

In patients with breast cancer, the
median time to an SRE was 26 months
with Zometa and has not yet been
reached with Xgeva. In patients with
other solid tumors, time to
development of an SRE was similar for
both Xgeva and Zometa. The most
common solid tumors were non-small
cell lung cancer, multiple myeloma,
kidney (renal) cancer, and small cell
lung cancer.

Amgen reports late-stage clinical trial
results showing Xgeva stopped
prostate cancer from spreading to the
bones of patients for about four
months longer than a placebo.
The results make Xgeva a stronger
competitor to Novartis AG's bone drug
Zometa, as Xgeva is more effective
than Zometa at treating bone
metastases.

Xgeva is also approved as an
osteoporosis drug under the name
Prolia.




JEVTANA, A CHEMOTHERAPY DRUG
FOR PROSTATE CANCER
In June 2010 the FDA  approved
Jevtana, a chemotherapy drug used in
combination with the steroid
prednisone to treat men with prostate
cancer.

Jevtana, made by French drug
company Sanofi-Aventis SA, was
reviewed under the FDA's priority
review program, which provides for an
expedited six-month review for drugs
that may offer major advances in
treatment.

Jevtana's safety and effectiveness was
established in a single, 755-patient
study. The study was designed to
measure overall survival, or the length
of time before death, in men who
received Jevtana in combination with
the steroid compared with those who
received the chemotherapy drug,
mitoxantrone, in combination with the
steroid.
It is the first and only therapy to show a
significant survival benefit in a very
difficult-to-treat group of men.

Jevtana is the first treatment for
advanced, hormone-refractory,
prostate cancer that has worsened
during or after treatment with
docetaxel, a commonly used drug for
advanced prostate cancer.

In prostate cancer, the male sex
hormone testosterone can cause
prostate tumors to grow. Drugs,
surgery, or other hormones are used
to reduce testosterone production or
to block it. Some men have hormone
refractory prostate cancer, meaning
the prostate cancer cells continue to
grow, despite testosterone
suppression. Different treatments are
needed for men with this type of
cancer.






NINE EMERGING THERAPIES FOR  
PROSTATE CANCER
A marketing  advisory firm for
pharmaceutical and healthcare issues
projects  that the launch and uptake of
nine emerging therapies will drive the
prostate cancer drug market to more
than double from nearly $4 billion in
2009 to $8.4 billion in 2019 in the
United States, France, Germany, Italy,
Spain, the United Kingdom and Japan.

It is predicted that sales of emerging
therapies, most notably Dendreon's
Provenge, will account for
approximately 57 percent of the total
prostate cancer market in 2019.
In addition to Provenge, market growth
will be driven by the uptake of Sanofi-
Aventis’s Jevtana, AstraZeneca’s
zibotentan, Johnson & Johnson’s
abiraterone, Amgen/GlaxoSmithKline/’s
Prolia, Medivation/Astellas Pharma’s
MDV-3100, Algeta/Bayer Schering
Pharma’s Alpharadin, Bristol-Myers
Squibb’s Sprycel and Celgene’s
Revlimid.



OTHER DEVELOPMENTS
Medarex's Ipilimumab along with a
standardized hormone treatment and
radiation therapy has shrunk tumor in
trial;