Blood clotting inhibitor:



FDA APPROVES COVIDIEN'S
SOLITAIRE DEVICE
In March 2012 Covidien  announced
that the Solitaire FR revascularization
device has been approved by the U.S.
Food and Drug Administration. The
Solitaire FR device is intended to
restore blood flow to the brain in
patients suffering acute ischemic
stroke by mechanically removing blood
clots from blocked vessels.

The approval  was based on the
results of the SWIFT clinical study.The
study compared  two devices.The
Solitaire FR device demonstrated
superior performance compared to the
Concentric Medical Merci Retriever
device, a commercially available
mechanical clot retriever.

The study randomly assigned 113
stroke patients at 18 hospitals to a
procedure to restore blood flow to the
brain with either the Solitaire FR
device or the Merci Retriever device
within eight hours of stroke onset. The
Solitaire FR device showed a 2.5x
benefit in restoring blood flow to the
brain, as determined by a blinded core
lab, a 1.7x improvement in post-stroke
neurological function and a 55%
reduction in mortality at 90 days.

"This new device heralds a new era in
acute stroke care," said Dr. Jeffrey L.
Saver, the SWIFT study's principal
investigator and a professor of
neurology at the David Geffen School
of Medicine at UCLA. "We are going
from our first generation of clot-
removing procedures, which were only
moderately good in reopening target
arteries, to now having a highly
effective tool. This really is a game-
changing result."

Stroke is a disease that affects the
arteries leading to and within the brain.
Ischemic stroke occurs when a blood
vessel that carries oxygen and
nutrients to the brain is blocked by a
clot. According to the American Heart
Association, stroke is the fourth
leading cause of death in the U.S. and
a leading cause of long-term disability.

This is good news for the
approximately 700,000 people each
year in the U.S. who suffer an acute
ischemic stroke.  

The Solitaire FR device received CE
Mark approval in Europe and has been
commercialized internationally by
Covidien since November 2009. The
Solitaire FR device will be available in
the U.S. from April 2012.

The Mansfield, Mass.-based medical
products conglomerate acquired
Solitaire as part of its $2.6 billion
purchase of ev3 Inc. in 2010.

In a separate news Stryker Corp.
acquired rival stroke device maker
Concentric in an all-cash $135 million
deal in September 2011.






FDA APPROVES BRILINTA, A NEW
BLOOD THINNER FROM
ASTRAZENECA
In July 2011 the FDA has approved
AstraZeneca's  blood thinner Brilinta
(ticagrelor) for acute coronary
syndromes.

The approval comes with a boxed
warning, however, stating that use of
ticagrelor with aspirin doses above 100
mg/day decreases the effectiveness of
the medication.

Brilinta is designed to keep blood
platelets from sticking together in order
to prevent blood clots that can lead to
heart attacks and strokes. It was
approved for patients diagnosed with
acute coronary syndrome. The product
will compete with the market-leading
anticlotting drug Plavix, marketed by
Sanofi-Aventis SA and Bristol-Myers
Squibb. Plavix is the second best-
selling drug globally after Pfizer Inc.'s
Lipitor with $8.8 billion in sales last
year.

The main international clinical study
AstraZeneca submitted to the FDA in
support of approval compared Brilinta
to Plavix in 18,624 patients in 43
countries who were being treated for a
blocked artery or heart attack. The
results showed Brilinta reduced the
combination of heart attacks, strokes
and death from cardiovascular causes
by 16% compared with Plavix after
patients were treated for a year. All
patients received aspirin. But the FDA
said when looking only at U.S. patients,
they had "worse results" with Brilinta,
which the agency said could have
been related to a higher aspirin dose.

In approving Brilinta  FDA said clinical
trials showed the drug "was more
effective than Plavix in preventing
heart attacks and death, but that
advantage was seen with aspirin
maintenance doses of 75 to 100
milligrams once daily."
Brilinta is sold under the brand name
Brilique outside the U.S.





XARELTO APPROVED BY THE FDA
In March 2012 researchers and J&J
officials said the 4,833-patient study
showed Xarelto was as effective as
customary dual therapy -- injections of
the clot-buster heparin given about the
same time as the blood-thinning pill
warfarin -- for treating the clots and
preventing new lung clots or
dangerous clots in the legs that can
break free and cause lung clots. The
vast majority of patients were treated
for more than six months.

The largest clinical trial ever
conducted among lung-clot patients
also showed that those taking Xarelto,
also known by its chemical name
rivaroxaban, experienced only half the
number of major bleeding incidents,
largely brain hemorrhages, as patients
receiving the heparin/warfarin
combination.

Brain bleeding is one of the most
worrisome side effects of warfarin, the
active ingredient of rat poison that has
been a mainstay anti-coagulant for
more than half a century.

Based on the favorable findings, J&J
said it plans in the second quarter of
2012 to ask U.S. regulators to approve
Xarelto for lung clots and leg clots.

Johnson & Johnson  and Bayer AG's  
Xarelto pill won U.S. approval for
orthopedic-surgery patients in July
2011, expanding the blood thinner’s
presence in a market to block clots
expected to reach as much as $15
billion annually.

The Food and Drug Administration
cleared Xarelto as an alternative for
preventing blood clots in patients after
hip or knee surgery.

“Shorter hospital stays following hip
and knee replacement have made
prevention of venous blood clots” a
concern for patients, said Paul Chang,
a vice-president for J&J’s Janssen
Pharmaceuticals unit, in the statement.
“Xarelto provides a safe and effective
oral treatment option.”

The drug will help protect the more
than 800,000 U.S. patients who
undergo hip and knee surgeries
annually and run the risk of developing
potentially fatal clots, the companies
said.

J&J, based in New Brunswick, New
Jersey, has U.S. rights to the medicine.
Bayer, with headquarters in
Leverkusen, Germany, sells the drug
in Europe, where the treatment won
approval in 2008 for use by hip- and
knee-surgery patients.




BLOOD THINNER PRADAXA
APPROVED BY FDA
In October 2010 German drugmaker
Boehringer Ingelheim won the first U.S.
approval for a new stroke-fighting
medicine that will compete in an
estimated $10 billion market for drugs
to replace the 65-year-old blood
thinner warfarin.
Boehringer's drug, Pradaxa, is cleared
for preventing strokes in patients with
a type of irregular heart beat.
The approval gives Boehringer a head
start over several other drugmakers,
including partners Bayer and Johnson
& Johnson, and Bristol-Myers Squibb
Co and Pfizer, that are working on
competing drugs.

Pradaxa and potential rivals are
alternatives to warfarin, a problematic
medicine originally developed as rat
poison.

Pradaxa is an anticoagulant that acts
by inhibiting thrombin, an enzyme in
the blood that is involved in blood
clotting. The FDA said the safety and
effectiveness of Pradaxa were studied
in a clinical trial comparing Pradaxa
with the anticoagulant warfarin. In the
trial, patients taking Pradaxa had fewer
strokes than those who took warfarin.

In August 2011 Boehringer Ingelheim’s
Pradaxa has become the first drug in
50 years to be approved in Europe for
stroke prevention in atrial fibrillation  
patients.

Pradaxa is already approved for
preventing blood clots in adults who
have undergone elective total hip or
elective total knee replacement
surgery.

But it can now be used in the EU for
the prevention of stroke and systemic
embolism in adult patients with non-
valvular AF with one or more risk
factors – an indication it has already
achieved in the US, Canada, Japan
and Australia.







SEMULOPARIN, THE ULTRA-LOW
WEIGHT HEPARIN
Mulsevo (semuloparin) from Sanofi, is
going to be ready for U.S. and EU
regulators in the third quarter of 2011
It is to treat  venous thrombo-embolism
events in cancer patients initiating a
chemotherapy regimen.

Patients undergoing major orthopedic
surgery are at increased risk of
developing a dangerous blood clot that
blocks veins, which is known as venous
thromboembolism (VTE). Without
treatment, the incidence of confirmed
deep-vein thrombosis, blood clots
within the veins of the legs and pelvis,
is  up to 40 to 60 per cent following
major orthopedic surgery.



HEPARIN'S MANUFACTURING
PROBLEMS  AND POSSIBLE
REPLACEMENT
Back in 2007 and 2008, tainted
heparin from China was responsible
for the deaths of over 80 people in the
U.S. If you had some sort of warm and
fuzzy reassurance that authorities were
looking into the matter, a new
congressional probe should quash that
feeling pretty quickly. The Wall Street
Journal reported that the probe, by two
congressmen from Texas, has found
that China never looked into the
heparin scandal at all.

Heparin is a blood thinner, and
chemically speaking, it’s a variably
sulfated glycosaminoglycan
polysaccharide composed of
alternating D-glucosamine and uronic
acid residues. Now, the blood thinner
term is sort of a misnomer- heparin
doesn’t actually thin the blood. What it
really does is inhibit coagulation-
prevent blood clots from forming or
reduce clots actively present.

Heparin does this by binding to a
protein called antithrombin III,
ultimately affecting the proteases
thrombin and Factor Xa, which both
play important roles in blood clot
formation.

We’ve known that heparin affects
blood clotting since 1916, but the stuff
has been extraordinarily tough to
replace. Today there exist many
different heparin-type products.
Garden-variety unfractionated heparin
is used in certain surgeries and in
kidney-dialysis patients. Fractionated
heparins like the low-molecular-weight
heparin Lovenox are used to prevent
and treat dangerous blood clots in the
leg veins of patients on bedrest or who
are having a hip or knee replacement.
And there are synthetic
pentasaccharides like fondaparinux,
essentially made from the business
end of heparin, which affect only
Factor Xa.

All of these products have the same
inconvenience- they all must be given
via injection. And outside the
fondaparinux-type drugs, it’s not easy
to manufacture them from scratch in a
lab because the structures are so
unwieldy and heterogenous.

There are a slew of drugs in the
pipeline that target Factor Xa or
thrombin directly, that are
straightforward molecular entities, and
that drugmakers would love to see
replace heparins and their coagulation
blocking buddy, warfarin, at least for
some applications. One of the potential
new drugs is Merck’s betrixaban.

Drugmakers have many reasons to
replace heparin and its ilk. But the
ability to manufacture a drug in a
controlled way has to be one of them.
Heparin itself might be cheap, but its
human cost has already been too high.



OTHER DEVELOPMENTS
Fruitflow, a paste made from tomato, it
speeds up blood flow just like aspirin,
made by Provexis,UK, can be found in
sirco, a health drink.

Otamixaban by SanofiAventis in Phase
2, competing with heparin;


Bivalirudin/Angiomax by Medicines Co;

Prasugrel by Eli Lily;

Atryn by GTC;

Enoxaparin (Lovenox) by
Sanofi/Aventis;