Tracleer and PPH News Encysive Drug Study Comes To An End
Staff Writer 2005-02-14 - Encysive Pharmaceuticals today announced topline results from the Company's multi- center, pivotal Phase III STRIDE-2 (Sitaxsentan To Relieve ImpaireD Exercise) trial. The trial was an effort to evaluate the safety and efficacy of Thelin (sitaxsentan) in patients with pulmonary arterial hypertension (PAH). The trial met its primary endpoint of improved six minute walk (6MW) distance in patients receiving a 100 mg dose of Thelin, with a placebo- subtracted improvement of 31.4 meters (p=0.03). A 50 mg dose of Thelin improved 6MW by 24.2 meters, and bosentan (Tracleer), currently the only approved oral agent for treating PAH, improved 6MW by 29.5 meters. As expected, placebo patients worsened in 6MW over the 18-week period of the trial. World Health Organization (WHO) functional class also improved significantly at the 100 mg dose of Thelin versus placebo (p=0.04). There were five clinical worsening events in the 100 mg patient group, seven events in the 50 mg group, 15 events in the bosentan group, and 13 for placebo. "We are extremely pleased with the performance of Thelin in STRIDE-2," commented Bruce D. Given, M.D., President and Chief Executive Officer of Encysive Pharmaceuticals. "We will present more details from this trial at appropriate medical meetings over the next several months and we are now focused on filing a New Drug Application (NDA) with the U.S. Food and Drug Administration in April 2005 to seek marketing authorization. This NDA submission will be closely followed by marketing applications in Europe and other territories." The 100 mg dose of Thelin continued to demonstrate an encouraging safety profile. Liver function abnormalities (elevation in liver enzymes to levels >3 times the upper limit of normal) occurred in 3% of patients in the 100 mg Thelin group, compared to 5% in the 50 mg Thelin group, 11% in the bosentan group and 6% in the placebo group. Premature discontinuations due to safety or efficacy occurred in four patients at the 100 mg Thelin dose, eight at the 50 mg Thelin dose, nine in the bosentan group and 11 in the placebo group. Of these patients, adverse events contributed to the discontinuation of two patients in the 100 mg Thelin group, four in the 50 mg group, six in the bosentan group and six in the placebo group. No serious bleeding episodes were reported in the study. Three patients had bleeding episodes in the presence of elevated international normalized ratios (INRs), one each on placebo, 50 and 100 mg of Thelin. The most frequent adverse events that occurred in patients receiving Thelin, which were more common than in placebo-treated patients, were peripheral edema (100 mg), insomnia (50 mg), chest discomfort (50 mg), sinus congestion (100 mg), nausea (50 mg), upper abdominal pain (50 mg) and increased INR (100 mg).
Encysive Pharmaceuticals Reports Fourth Quarter and Year End 2004 Results; Conference Call Scheduled for Today at 4:30 p.m. EST
HOUSTON, Feb. 17 /PRNewswire-FirstCall/ -- Encysive Pharmaceuticals (Nasdaq: ENCY) today announced financial results for the fourth quarter and year ending December 31, 2004.
"Our success with Thelin(TM) in STRIDE-2 for the treatment of pulmonary arterial hypertension marks the culmination of an extremely productive year for Encysive," said Bruce D. Given, M.D., President and Chief Executive Officer of Encysive Pharmaceuticals. "This data builds upon the important clinical progress we have achieved over the course of 2004 in STRIDE-4 and STRIDE-6 with Thelin and we're well positioned to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) and other regulatory authorities." Fourth Quarter 2004 Financial Overview * For the fourth quarter of 2004, the Company reported a net loss of approximately $14.7 million, or $0.26 per basic and diluted share,
compared to a net loss of $8.7 million, or $0.19 per basic and diluted share, for the same period in 2003. The increase in net loss in the fourth quarter of 2004 was due primarily to an increase in operating expenses of approximately $8.0 million from the same period in 2003, primarily reflecting the increased costs of the ongoing clinical trials, and preparation work for filing a NDA for Thelin. The increase in net loss per share was also impacted by the higher number of outstanding shares in the quarter due to the completion of public offerings of common stock in December 2003 and September 2004. * Revenues in the fourth quarter of 2004 were approximately $5.0 million, compared to $2.7 million in the comparable quarter of 2003. The increase in the fourth quarter of 2004 was primarily due to the Company's royalties earned on net sales of Argatroban by
GlaxoSmithKline (GSK) which increased to $4.6 million compared to
$1.8 million in the comparable quarter of 2003, an increase of 156%. In addition to increased net sales of Argatroban in the fourth quarter of 2004, royalties increased due to additional royalties earned for attainment of a net sales threshold by GSK. Royalties are paid based on a tiered structure that must be attained annually. * Cash, cash equivalents and investments at December 31, 2004 were $69.1 million, including $35.6 million in net proceeds from a public offering of common stock completed in September 2004, compared to $85.5 million at December 31, 2003. Year 2004 Financial Highlights * Net loss for the year ended December 31, 2004 was approximately $54.7 million, or $1.01 per basic and diluted share, compared to a net loss of $35.3 million, or $0.80 per basic and diluted share, for fiscal 2003. The increase in net loss and loss per share for the year 2004 was primarily due to the increase in research and development expense related to our late stage clinical trial program for Thelin. The increase in net loss per share was also impacted by the higher number of outstanding shares due to the completion of public offerings of common stock in December 2003 and September 2004. * Total research and development expenses, including Encysive, L.P., increased from $31.8 million in 2003 to $58.2 million in 2004. The increase in research and development expenses for the year 2004 was primarily related to our late stage clinical trial program for Thelin. * Revenues in 2004 were $13.8 million compared to $11.6 million in 2003. Research agreement revenue was approximately $1.5 million in 2004 as compared to $3.0 million in 2003 due to the conclusion in June of 2004 of research payments in our agreement with Schering-Plough. The Company's royalties on net sales of Argatroban increased to $10.6 million in 2004, compared to $5.4 million in 2003, an increase of 97% on net sales of $55.3 million. In addition to increased net sales of Argatroban in 2004, royalties increased due to additional royalties earned for attainment of a net sales threshold by GSK. Royalties are paid based on a tiered structure that must be attained annually. Approximately 64% of the increase in royalties was due to increases in net sales and 36% was due to the threshold attainment. Recent Events * The Company reported on February 14, 2005 that STRIDE-2, its pivotal Phase III safety and efficacy trial, conducted under a special protocol assessment with the FDA, met the primary endpoint of improved six minute walk (6MW) in patients receiving 100 mg of Thelin. The 100 mg group saw a statistically significant increase of 31.4 meters over placebo (p=0.03). Bosentan (Tracleer(R)), the only approved oral product for pulmonary arterial hypertension, increased the 6MW by 29.5 meters, while patients on placebo saw their conditions deteriorate. A 50 mg dose of Thelin was also evaluated to explore the lower end of the dose response curve but did not achieve statistical significance versus placebo and the Company does not anticipate seeking registration for this dose in adults. Importantly, Thelin demonstrated a favorable safety profile. The 100 mg dose of Thelin was associated with a 3% rate of liver function abnormality in the 18-week study, compared to 11% for bosentan and 6% for placebo. In the study, patients were randomized to receive placebo once daily, 100 mg of Thelin once daily, 50 mg of Thelin once daily, or twice daily bosentan, as indicated by its package insert. Additional data will be presented at the annual meeting of the American Thoracic Society on May 23, 2005 in San Diego. 2004 Company Highlights * The Company announced topline results from STRIDE-4 showing 100 mg Thelin as statistically more active than 50 mg, with a favorable safety profile. Due to an unexpected placebo response and the small size of the trial, 100 mg of Thelin(R) did not achieve significance versus placebo in this non-pivotal trial. * Thelin received Orphan Drug Designation in the United States and Europe. * Encysive reported positive results from the STRIDE-6 study of Thelin in PAH patients who discontinued treatment with bosentan due to lack of efficacy or for safety reasons. * Results from a drug interaction study of Thelin and sildenafil
(Viagra(R)) demonstrated a pharmacokinetic drug-drug interaction, which the Company believes is unlikely to necessitate dosage adjustments of either compound. * Thelin data was presented at leading medical meetings in the United States and Europe, including the American College of Rheumatology Annual Scientific Meeting, European Respiratory Society 14th Annual Congress, European Society of Cardiology Annual Congress, annual
meetings of the American College of Cardiology and American Heart Association (AHA) and the 100th International Conference of the American Thoracic Society. * Encysive's first scientific symposia were held at the American College of Chest Physicians (CHEST) and AHA meetings. * The Company successfully completed a common stock offering raising $36.5 million. Year 2005 Financial Guidance
As a result of the new data from STRIDE-2, Encysive is now in the process of forecasting financial guidance based on moving Thelin forward towards regulatory filings, further R&D and pre-commercialization activities. The Company expects to provide 2005 financial guidance in the first half of 2005. Upcoming Events * BIO CEO & Investor Conference -- February 23-24, 2005. * SG Cowen's 25th Annual Health Care Conference -- March 14-17, 2005. * The Company has previously guided an expectation for filing a NDA with the FDA in April 2005. Based on current data collection progress, Encysive believes that the NDA may be submitted in May 2005. Regulatory submissions in other territories are expected to follow thereafter. * Presentation of abstracts at the American Thoracic Society Annual Meeting -- May 20-25, 2005 Conference Call Information
Encysive Pharmaceuticals will host a conference call today at 4:30 p.m. EST. To participate in the call, dial (612) 288-0318; passcode Encysive Pharmaceuticals. The conference call is also being webcast and can be accessed via Encysive's web site at http://www.encysive.com. A replay of the call will be available until Monday, February 21, 2005 at 11:59 p.m. EST at (320) 365-3844; access code 769973. Additionally, a replay of the webcast will be available on the Company's web site through March 18, 2005. 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 versus the endothelin B 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/lung or lung transplantation. PAH is 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 Inc.
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, including as Texas Biotechnology Corporation, has filed with the Securities and Exchange Commission. Encysive undertakes no duty to update or revise these forward-looking statements. ENCYSIVE PHARMACEUTICALS INC. AND SUBSIDIARIES
SELECTED FINANCIAL DATA
Amounts in thousands (except per share data) Consolidated Summary of Operations Three Months Ended Twelve Months Ended
December 31, December 31,
2004 2003 2004 2003
Revenues $ 4,970 $ 2,700 $ 13,778 $ 11,557 Operating expenses: Research and development 16,197 10,311 58,159 29,420
Purchase of in-process
research and development --- --- --- 8,363
Equity in loss of
Encysive, L.P. --- --- --- 2,386
General and administrative 3,993 1,882 12,113 9,134
Total expenses 20,190 12,193 70,272 49,303
Operating loss: (15,220) (9,493) (56,494) (37,746) Investment income, net 298 324 1,079 1,228 Minority interest in Revotar 268 457 755 1,225
Net loss $(14,654) $ (8,712) $(54,660) $(35,293) Net loss per common share:
(basic and diluted) $ (0.26) $ (0.19) $ (1.01) $ (0.80) Weighted average common
shares outstanding: 57,397 44,875 53,942 44,072
(basic and diluted) Condensed Consolidated Balance Sheets Dec. 31, Dec. 31,
2004 2003
Cash, cash equivalents, investments
and accrued interest $ 69,101 $ 85,489
Other assets 11,671 8,909
Total assets 80,772 94,398 Total liabilities 16,927 15,917
Deferred income 1,680 2,240
Minority interest in affiliate 628 1,384
Stockholders' equity 61,537 74,857
Total liabilities and stockholders' equity $ 80,772 $ 94,398 SOURCE Encysive Pharmaceuticals
Web Site: http://www.encysive.com
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