HOUSTON, Feb. 17 /PRNewswire-FirstCall/
-- Encysive Pharmaceuticals
today announced the publication of an article titled "Sitaxsentan Therapy
for Pulmonary Arterial Hypertension" in the February 15 issue of the
American Thoracic Society's American Journal of Respiratory and Critical
Care Medicine (AJRCCM) (Vol. 169, pp. 441-447). The full article can be found
on
American Thoracic Society's website at http://ajrccm.atsjournals.org
.
The reported study is based on Encysive's Phase
IIb/III STRIDE-1 (Sitaxsentan To Relieve ImpaireD Exercise) clinical study in
Pulmonary Arterial Hypertension (PAH). The author and lead investigator of the
study, Robyn J. Barst, M.D., Director, New York Presbyterian Pulmonary
Hypertension Center, Columbia University College of Physicians and Surgeons,
New York, NY, concluded that sitaxsentan at doses of 100 mg or 300 mg
administered orally once daily improved six-minute walk distance by 35 and 33
meters, respectively, after 12 weeks of treatment in PAH patients. In
addition, New York Heart Association (NYHA) functional class, cardiac output
and pulmonary vascular resistance also improved.
The 178 patient STRIDE-1 trial included a
broader range of patients than previously studied in the comparable
multi-center trial with the marketed, non-selective endothelin receptor
antagonist bosentan. Sitaxsentan is a selective endothelin A receptor
antagonist.
"While each of the patient groups appeared
to have benefited from sitaxsentan treatment, when data on the STRIDE-1
patients who would have qualified for inclusion in the bosentan BREATHE-1
trial were analyzed, the treatment effect for sitaxsentan increased to 65
meters in the six-minute walk test," reported Dr. Barst. "This
compares to the reported 44 meter treatment effect for bosentan in the
213-patient pivotal BREATHE-1 study. The ongoing pivotal study, STRIDE-2,
evaluates both endothelin receptor antagonists."
"This study published in the AJRCCM
supports our strategy in developing sitaxsentan," commented Bruce D.
Given, M.D., President and CEO of Encysive. "Our second pivotal study,
STRIDE-2, is currently enrolling patients with Class II-IV pulmonary arterial
hypertension in North America and Europe. We believe results from this study,
combined with results from other trials, will further define the ability of
sitaxsentan to successfully treat a broad range of patients diagnosed with PAH."
About STRIDE-1 and STRIDE-2
The STRIDE-1 trial was a randomized,
double-blind, placebo-controlled, 12-week study in 178 patients. Included were
patients with NYHA Class II-IV primary pulmonary hypertension, PAH related to
connective tissue disease or PAH related to congenital heart disease; there
was no upper limit to baseline walk for inclusion in the study, i.e. patients
with baseline six-minute walk >450 meters were not excluded. Patients
received either sitaxsentan 100 mg, sitaxsentan 300 mg or placebo treatment
once a day and were treated for 12 weeks. Sitaxsentan 100 mg and 300 mg
provided similar improvements in exercise capacity (six-minute walk),
functional class and hemodynamics.
Of the 178 patients enrolled in STRIDE-1, none
of the patients in the 100 mg group discontinued due to adverse events or for
other reasons, versus five patients from the placebo group and seven from the
300 mg group. The most frequent adverse events that occurred in patients
receiving sitaxsentan and that were more common than in placebo-treated
patients were headache, peripheral edema, nausea, nasal congestion and
dizziness. Liver abnormalities have previously been recognized as
complications related to the endothelin antagonist class of drugs. Liver
abnormalities in the STRIDE-1 trial were defined as elevated serum
aminotransferase values that were more than three times normal. Incidences of
liver abnormalities in STRIDE-1, which reversed in all cases, were 3% for the
placebo group, 0% for the sitaxsentan 100 mg group and 9.5% for the
sitaxsentan 300 mg group. When experiences from STRIDE-1 and its extension
trial, resulting in total patient exposures of as long as 58 weeks are
considered, 5% of patients receiving 100 mg and 21% receiving 300 mg of
sitaxsentan developed elevations. All elevations resolved with discontinuation
of study drug.
Given the similarity in efficacy between the
100 mg and 300 mg dose groups and the improved safety profile of the 100 mg
dose, 100 mg once daily has been selected as the maximum dose in the ongoing
clinical program.
STRIDE-2 is a 240 patient trial including
patients with WHO (NYHA modified for PAH) Class II-IV PAH of primary or
secondary etiologies (due to collagen vascular disease or certain congenital
heart defects) with an entry six-minute walk distance of less than or equal to
450 meters. Patients are being randomized to receive placebo, 50 or 100 mg of
sitaxsentan or bosentan. The STRIDE-2 program is being conducted under a
Special Protocol Assessment with the U.S. Food and Drug Administration.
About Sitaxsentan and PAH
Sitaxsentan is a small molecule that
antagonizes 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.
Sitaxsentan is a highly selective endothelin A receptor antagonist and is 6500
times more selective for endothelin A than endothelin B receptors.
Pulmonary arterial hypertension 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
shortens life-expectancy. PAH is estimated to afflict around 100,000 people
worldwide, many of whom are young adults.
About Encysive Pharmaceuticals
Encysive Pharmaceuticals, 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,
sitaxsentan, 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: 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 of revise these forward-looking statements. Source:
Encysive Pharmaceuticals