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Encysive Pharmaceuticals

Thelin May Offer Alternative for PAH Patients Who Have Failed on Bosentan, According to Data Presented at European Respiratory Society Congress

Houston (ots/PRNewswire)

- Study Shows Liver Toxicities Experienced by Patients on Bosentan
Were Not Experienced on Thelin
Encysive Pharmaceuticals (Nasdaq: ENCY) today announced the
presentation of new clinical data on Thelin(TM) (sitaxsentan) in
pulmonary arterial hypertension (PAH), at the European Respiratory
Society (ERS) 14th Annual Congress (September 4-8, 2004) in Scotland.
Data from this single center experience suggests that Thelin may
offer an alternative for PAH patients whose conditions are worsening
on bosentan. Two other abstracts were presented at the ERS meeting on
Thelin.
Data from this first study was presented by clinical investigator
Adaani Frost, M.D., Baylor College of Medicine, Houston, Texas.
Entitled, "Sitaxsentan Sodium for the Treatment of Pulmonary Arterial
Hypertension in Patients Failing Bosentan: Preliminary Single Center
Data," the trial showed that 10 out of 11 PAH patients who had failed
on bosentan due to clinical deterioration or liver toxicities
improved or stabilized when given Thelin oral therapy. All 10
patients are continuing on Thelin today, some as long as 10 months.
Eight (8) patients in the study who had deteriorated on bosentan
were given Thelin 100 mg and followed for up to 12 weeks. Seven
patients stabilized or experienced improvement in the six-minute walk
test (6MW), a standard measurement of function in patients with PAH.
One patient in the study discontinued Thelin treatment due to
continued disease progression and had no evaluable 6MW measurements.
Three other patients were enrolled after failing bosentan therapy due
to liver toxicity. All three improved clinically on Thelin without
recurrence of their liver abnormalities. One patient who had
clinically deteriorated on bosentan experienced a single occurrence
of an abnormal liver function test. This patient has continued on
Thelin without a recurrence.
"As the first generation, nonselective endothelin receptor
antagonist, bosentan has provided an important treatment option for
patients with PAH. We do, however, see up to one-third of patients
come off this therapy due to lack of efficacy or liver toxicities,"
said Dr. Frost. "While trials are ongoing, sitaxsentan, an oral ETA
selective endothelin receptor antagonist, may provide value to newly
diagnosed PAH patients. The exciting potential from this study,
however, is the opportunity for sitaxsentan to salvage some of the
one-third of patients who are currently failing bosentan therapy."
"The clinical strategy for Thelin is to expose a broad and
multi-faceted patient group to our selective endothelin antagonist,"
said Terrance Coyne, M.D., Vice President and Chief Medical Officer
of Encysive Pharmaceuticals. "In addition to alternatives for de novo
patients, one of the greatest and most immediate needs in PAH today
is the development of effective alternative treatments for those
failing on current options. We believe Thelin, with its selective
mode of action, has the potential to be an important new option for
these difficult-to-treat patients."
Additional Data Presentations
The second abstract, entitled, "Long-Term Sitaxsentan Therapy in
PAH," Drs. Horn, Langleben, et al., demonstrated that Thelin was
similarly effective in improving symptoms at doses of 100 mg and 300
mg. Given the better safety profile for the 100 mg dose, the data
supports the selection of 100 mg as the maximum dose.
The third abstract, entitled, "Efficacy of Sitaxsentan, an
Endothelin-A Receptor Antagonist in PAH in Traditional Versus
Expanded Study Populations," by Drs. Frost, Langleben et al., was
also presented at the meeting. The data supports the existence of a
"ceiling effect" as provided for in traditional PAH trial designs.
Frequent exclusion of patients with milder PAH, in order to increase
treatment effect sizes and statistical power, is customary when using
6MW as the endpoint. STRIDE-1, a 12-week, randomized, double-blind,
178-patient trial employing placebo and Thelin at 100 mg or 300 mg
doses, included patients with NYHA functional class II, congenital
heart disease and a baseline 6MW > 450m-groups often excluded from
previous trials. For patients meeting traditional enrollment criteria
(NYHA class III or IV and 6MW less than or equal to 450m at baseline
with idiopathic PAH or PAH-related to connective tissue disease),
Thelin produced a robust increase in 6MW of 65 meters (p=0.0002) vs.
34 meters (p=0.0005) in the intent-to-treat patient group.
About Thelin and PAH
Thelin is a small molecule that blocks the action of endothelin, a
potent mediator of blood vessel constriction and growth of smooth
muscle in vascular walls. Endothelin receptor antagonists may prove
to be effective in the treatment of a variety of diseases where the
regulation of vascular constriction is important. Thelin is
6,500-fold selective in the targeting of the endothelin A receptor.
Pulmonary arterial hypertension (PAH) is a condition that involves
high blood pressure and structural changes in the walls of the
pulmonary arteries, which are the blood vessels that connect the
right side of the heart to the lungs. PAH causes shortness of breath,
limits activity, and is eventually fatal unless treated successfully
with heart and lung transplants. Primary and secondary PAH are
estimated to afflict approximately 80,000 to 100,000 people
worldwide, many of whom are children and young women.
Side effects of Thelin seen in the program to date, and which
occurred more frequently than in placebo, include liver dysfunction
(increased ALT and AST), headache, edema, constipation, nasal
congestion and flushing. Because Thelin inhibits the metabolism of
warfarin, the dose of warfarin should be adjusted downward when
co-administered with Thelin.
About Encysive Pharmaceuticals
Encysive Pharmaceuticals Inc., a biopharmaceutical company focused
on the discovery, development and commercialization of novel drugs,
is recognized for our expertise in small molecule drug development
and vascular biology. Argatroban, our first FDA-approved product, is
being marketed by GlaxoSmithKline for heparin-induced
thrombocytopenia. Encysive Pharmaceuticals is in Phase III
development of the endothelin antagonist, Thelin, for pulmonary
arterial hypertension. Our majority-owned affiliate, Revotar
Biopharmaceuticals AG, is in Phase II development with the selectin
antagonist bimosiamose in asthma, psoriasis and atopic dermatitis.
Encysive Pharmaceuticals has several other research and development
programs ongoing for a range of cardiovascular and inflammatory
diseases. To learn more about Encysive Pharmaceuticals please visit
our web site: http://www.encysive.com.
This press release contains "forward-looking statements" within
the meaning of Section 27A of the Securities Act of 1933, as amended,
and Section 21E of the Securities Exchange Act of 1934, as amended.
These forward-looking statements are subject to certain risks, trends
and uncertainties that could cause actual results to differ
materially from those projected. Among those risks, trends and
uncertainties are timing and cost of our clinical trials, attainment
of research and clinical goals and milestones of product candidates,
attainment of required government approvals, sales levels of our
products and availability of financing and revenues sufficient to
fund development of product candidates and operations. In particular,
careful consideration should be given to cautionary statements made
in the various reports Encysive Pharmaceuticals, including as Texas
Biotechnology Corporation, has filed with the Securities and Exchange
Commission. The Company undertakes no duty to update or revise these
forward-looking statements.
Web site: http://www.encysive.com

Contact:

Investors: Ann Tanabe, Director, Investor Relations and Corporate
Communications, Encysive Pharmaceuticals, +1-713-796-8822; or Hershel
Berry, The Trout Group, +1-415-392-3385, for Encysive
Pharmaceuticals; or Media: Daniel Budwick, BMC Communications,
+1-212-477-9007, ext. 14, for Encysive Pharmaceuticals