Sitaxsentan May Stack Up Well Against Other Pulmonary Arterial Hypertension Treatments
October 21, 2002. ICOS (NASDAQ: ICOS) and Texas Biotechnology’s (NASDAQ: TXBI) 178-patient, 12-week, double-blind, placebo-controlled, phase IIb/III STRIDE (Sitaxsentan To Relieve ImpaireD Exercise in Pulmonary Arterial Hypertension) trial demonstrates that sitaxsentan has a reasonable risk/benefit profile. The results make sitaxsentan a contender for a place in the competitive pulmonary arterial hypertension marketplace. Reassuring data regarding the reversibility of associated liver abnormalities, a class effect of endothelin blockers, were offered. However, clinically significant advantages over competing endothelin blockers are unlikely to be observed for, at least, more severely affected patients.  Sitaxsentan’s treatment effect profile was evaluated for patients with New York Heart Association (NYHA) class II, III and IV pulmonary arterial hypertension (PAH). Study subjects were randomized to receive sitaxsentan 100 mg, sitaxsentan 300 mg, or placebo treatment once a day. The investigation’s primary endpoint was change in percent of predicted peak VO2 (“oxygen uptake,” a measure of metabolic and cardiorespiratory functional capacity). Change in 6-minute walk distance was a secondary endpoint.  For the primary endpoint, a statistically significant improvement for the 300 mg dose group compared with placebo was achieved that represented a 7% relative improvement. The primary endpoint was not met for the 100 mg recipients. For the secondary endpoint, a 9% relative improvement was observed, and the variance from placebo effect was significant for recipients of both doses. The 300 mg dose did not provide a larger magnitude of therapeutic effect than the 100 mg dose. Both doses showed statistically and clinically significant advantages over placebo in terms of NYHA class improvement. The adverse effect profile was predictable and manageable.  Overall, including data from the sitaxsentan program that includes a maximum of 55 weeks follow-up, the greatest benefit/risk ratio appeared to favor the 100 mg dose, as its associated rate of reversible liver abnormalities was considerably more appealing than that for the 300 mg dose. However, for more severely impaired PAH patients, the value of the additional cardiopulmonary reserve offered by the 300mg dose might shift the ratio in favor of administration for a significant proportion of patients.  The PAH competitive landscape in the U.S. market features Actelion’s (Swiss: ATLN) Tracleer (bosentan), also an endothelin antagonist, as well as GlaxoSmithKine’s (NYSE: GSK) Flolan (epoprostenol) and United Therapeutics (NASDAQ: UTHR) and Medtronic’s (NYSE: MDT) Remodulin (treprostinil sodium), which are prostacyclins. Remodulin is administered subcutaneously via an infusion device. Flolan is delivered intravenously. Tracleer has a lower attributable cost profile than Flolan. However, Tracleer’s potential adverse effects include liver damage and birth defects. Patients taking Tracleer must have monthly blood tests to catch early signs of liver damage and female patients on Tracleer need monthly pregnancy tests.  Pulmonary hypertension, in its primary form, strikes one or two people per million. Secondary forms of pulmonary hypertension, which are more frequently observed in the clinic, are usually adverse effects of the now-banned diet pills Redux and fen-phen or a complication of lupus, progressive systemic sclerosis (PSS, scleroderma) and other rheumatologic disorders. Pulmonary hypertension is high blood pressure in the pulmonary (lung and related) arteries and/or pulmonary artery branches, blood vessels normally under considerably lower pressures than those of the aorta and aorta branches that go to the rest of the body. Pulmonary hypertension can lead to irreparable and devastating lung damage.
DISCLAIMER The above information transmitted via BioPortfolio has been provided by the original publishers BiotechTracker ("BT") a financial information, news, and software service focusing on event-driven biotechnology and pharmaceutical research. The Service is provided by DPBT, LLC ("DPBT"). a joint venture formed between BT Investor, Inc. and PCS Research Technology, Inc. It is not guaranteed as to completeness or accuracy by BioPortfolio, the BT publishers, or any person. Such Information is neither an offer to sell nor a solicitation to buy the securities of any company. Opinions expressed are subject to change without notice. The Information and views provided by BT are prepared by BT employees and in no way reflect the views or efforts of BioPortfolio Limited., any of BioPortfolio's employees or officers. BioPortfolio, and BioPortfolio's employees and officers, as well as BT’s employees and officers, in no way accept responsibility for any of the BT content published on www.bioportfolio.com/.  While all reasonable care has been taken to ensure that the Information contained herein is presented in good faith, and is not untrue or misleading at the time of publication, BioPortfolio, and BT make no representation as to its accuracy or completeness and it should not be relied upon as such. The Information is supplied on the condition that the reader or any other person receiving the Information will make his or her own determination as to its suitability for any purpose prior to any use of the Information. From time to time, BioPortfolio and any officers or employees of BioPortfolio, as well as BT, and any officers or employees of BT, may, to the extent permitted by law, have a position or otherwise be interested in any transactions, in any investments (including derivatives) directly or indirectly the subject of this report. Also BioPortfolio and BT may, from time to time solicit business from any company mentioned in this report. This report is provided solely for the information of viewers of BioPortfolio and/or viewers and subscribers of BT and BioPortfolio information services, who are expected to make their own investment decisions without reliance on this report. Neither BioPortfolio nor any officer or employee of BioPortfolio, nor BT, or any officer or employee of BT, accepts any liability whatsoever for any direct, indirect, special or consequential damages or loss arising from any use of this report or their contents. This report may not be reproduced, distributed or published by any recipient for any purpose without the prior express consent of the publishers. Nothing contained herein shall be construed as conferring by implication, estoppel or otherwise any license or right under any patent, trademark or copyright of BioPortfolio, BT or any third party.  The value of the investment(s) to which this report relates and their income yield(s) may go up or down. The investment(s) referred to in this report may not be suitable for private investors: if you are in any doubt you should seek advice from your investment advisor. Changes in rates of currency exchange may have an adverse effect on the value, price or income of investments. Statements as to past performance of any investment are not a guide to future performance. The levels and bases of taxation can change, and if you are in doubt you should seek independent professional advice. In some cases it may be difficult for you to sell or realize your investment or to obtain reliable information about its value or the extent of the risks to which you are exposed.  THIS INFORMATION IS PROVIDED "AS IS" AND NO REPRESENTATIONS OR WARRANTIES, EITHER EXPRESS OR IMPLIED OF ACCURACY, MERCHANTIBILITY FITNESS FOR A PARTICULAR PURPOSE OR OF ANY OTHER NATURE ARE MADE WITH RESPECT TO THIS INFORMATION OR TO ANY EXPRESSED VIEWS PRESENTED IN THIS INFORMATION.