Tracleer and PPH News Actelion Ltd -- Scientific Publication on Long-Term Bosentan Use in PPH European Respiratory Journal -- Outcome Data Analysis of First-Line Use of Bosentan (Tracleer) in Patients With Advanced Primary Pulmonary Hypertension -- Long-Term Benefits of Bosentan Therapy Confirmed ALLSCHWIL, Switzerland, Feb. 1, 2005 (PRIMEZONE) -- Actelion Ltd (Other OTC:ALIOF) (SWX:ATLN) announced today the publication of the scientific paper evaluating disease outcome of patients with advanced primary pulmonary arterial hypertension receiving Tracleer(r) (bosentan). Outcome in patients receiving first-line bosentan therapy was compared to patient outcomes whose disease progression was documented in a historical database of the U.S. National Institute of Health (NIH). Commenting on the publication, lead investigator Dr. Vallerie McLaughlin, University of Michigan, Ann Arbor, MI, USA, said, "The present study suggests that the treatment of first-line bosentan therapy followed by the addition of other pulmonary arterial hypertension (PAH) therapies, if needed, improves survival in patients with advanced primary pulmonary hypertension." Dr McLaughlin added that, "Given the ease of administration and favorable side-effect profile, the strategy of treatment with first-line bosentan should be considered for World Health Organisation (WHO) functional class III primary pulmonary hypertension patients." The study "Survival with first-line bosentan in patients with primary pulmonary hypertension" by V. McLaughlin et al. has been published in the European Respiratory Journal Volume 25, Issue 2, pages 244-249. This publication supports earlier findings by Olivier Sitbon in Chest, 2003 July, Volume 124(1), pages 247-254. This shorter and smaller study had found that long-term treatment with bosentan was well tolerated and provided sustained benefits on exercise capacity and hemodynamics in patients with PAH. Additionally, recent guidelines from The American College of Chest Physicians (ACCP) published in Chest, 2004 July, Volume 126(1), pages 35S-62S by Badesch et al., now recommend bosentan as a first-line therapy for WHO Functional Class III PAH patients. The publication findings in detail A total of 245 patients with PAH were enrolled in the two placebo-controlled trials. At the end of these studies, all patients were offered bosentan therapy. The results published today are from the long-term follow-up of the 169 patients with primary pulmonary hypertension (PPH). The objective of this study was to evaluate the effect of first-line bosentan therapy followed by additional therapies if needed, on survival in PPH patients compared with NIH estimates. An additional objective was to explore prognostic factors for survival in bosentan-treated PPH patients. Patients who participated in these studies have now received bosentan as first-line therapy for up to three years. Data on survival and alternative treatments were collected from September 1999 to December 2002. Observed survival up to 36 months was reported as Kaplan-Meier estimates and compared with predicted survival as determined for each patient by the National Institutes of Health (NIH) Registry formula. In assessing the long-term benefit of bosentan, Dr. McLaughlin and her U.S. and European colleagues compared the survival in bosentan-treated patients to the survival that would have been predicted based on past clinical experience. Results showed that survival in the bosentan treated patients was 96 percent at one year and 89 percent at two years. In comparison, the expected survival without treatment was 67 percent at one year and 58 percent at two years. A significant feature of the study was that 85 percent and 70 percent of patients were still on bosentan alone, at one year and two years of follow up respectively, without the need for additional therapies. About Tracleer(r) in Pulmonary Arterial Hypertension (PAH) Tracleer(r), the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH) and made available by Actelion subsidiaries in the United States, the European Union, Australia, Canada, Switzerland, Israel, Hong Kong, Malaysia, Singapore and Brazil. In Japan, Tracleer(r) has been filed for marketing approval. In clinical trials leading to the marketing approval of the drug, approximately 11% of PAH patients receiving Tracleer(r) experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or of childbearing age who do not use a reliable method of contraception, must not take Tracleer(r). About Pulmonary Arterial Hypertension (PAH) Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The function of the heart and lungs is severely compromised, manifested by a limited exercise capacity, and, ultimately, a reduced life expectancy. Approximately 100,000 people in Europe and the United States are afflicted with either primary or secondary forms of the disease related to conditions or tissue disorders that affect the lungs, such as scleroderma, lupus, HIV/AIDS or congenital heart disease. Actelion Ltd Actelion Ltd is a biopharmaceutical company with its corporate headquarter in Allschwil/Basel, Switzerland. Actelion's first drug Tracleer(r), an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer(r) through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union as well as Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium -- the single layer of cells separating every blood vessel from the blood stream. Actelion focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN). CONTACT: Actelion Ltd
Roland Haefeli
Investor Contact
+41 61 565 64 58
(650) 624-6936
Peter Engel
Media Contact
+41 61 565 66 28
(650) 624-6996
http://www.actelion.com
Tracleer helps PAH patients with scleroderma
June 13 2005(Reuters) - Tracleer has shown positive long-term impact in treating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (scleroderma), the drug-maker Actelion said on Friday.
In abstracts presented at a European rheumatology conference, Actelion said that data showed that Tracleer, also known by its generic name bosentan, helped patients do better in physical performance tests over short and long periods.
"Over 12 or 16 weeks, patients treated with bosentan improved by 14.6 metres in the 6-minute walk test while patients in the placebo group deteriorated by 22.2 metres," Actelion said.
The company said that as many as 15 percent of scleroderma patients develop PAH and the prognosis is extremely poor. Without treatment there is a median survival rate of just 12 months for scleroderma patients diagnosed with PAH, the Swiss biotech firm said.
European Panel Thumbs-Up On Encysive's PAH Therapy Thelin
By Randall Osborne
West Coast Editor
A surprise positive opinion from regulators in Europe regarding Encysive Pharmaceuticals Inc.'s Thelin took the sting out of the less happy news from U.S. regulators earlier this year, and Wall Street rewarded the company with a stock boost of about 35 percent.
Encysive's shares (NASDAQ:ENCY) closed Friday at $5.82, up $1.50.
The Committee for Medicinal Products for Human Use, advising the European Agency for the Evaluation of Medicinal Products, recommended approval of Thelin (sitaxentan) for pulmonary arterial hypertension (PAH).
A decision from the European Commission is expected within about 90 days. If approved, the endothelin blocker could be marketed in all 25 member states of the European Union.
In late March, Encysive heard from the FDA that the drug is approvable in the U.S., but more trials must be done, and the agency's demand knocked almost half the value off the company's shares, which closed that day at $4.60. Encysive submitted a complete response last month. (See BioWorld Today, March 28, 2006.)
As analyst opinion ranged all over the map, a spokesperson for Houston-based Encysive said the company is choosing not to comment on the news from Europe.
"The biggest problem is that the company isn't disclosing the reason behind the approvable letter," either, said Andrew Fein, analyst with C.E. Unterberg, Towbin, who maintained his "underperform" rating.
Progress in Europe means that "to some extent, you can rule out worst-case scenario rumors - severe bleeding and all that - but, fundamentally, it probably doesn't change anything," Fein told BioWorld Today, adding that Encysive will be able to launch only in the UK and Germany without going through the pricing process, which can take "months to over a year."
Phil Nadeau, analyst with Cowen and Co. LLC, upgraded Encysive's shares from "neutral" to "outperform" on the news from Europe, noting in a research report that "most had assumed that the European regulators, similar to the U.S., would request additional clinical trials prior to approval" but how "it seems very likely" Thelin will be marketed in Europe by the fourth quarter.
Nadeau raised his ex-U.S. sales estimates for Thelin from zero to $40 million for next year, from $32 million to $70 million for 2008, from $58 million to $100 million for 2009, and from $84 million to $135 million for 2010.
Also upgrading were Oppenheimer & Co. and Rodman & Renshaw.
Others, like Fein, proved more circumspect. Mark Monane at Needham & Co. LLC kept his "hold" rating on Encysive because of the problems in the U.S., though he conceded in a research report that reimbursement is "unusually strong" for PAH in Europe.
Jennifer Chao, with Deutsche Bank, maintained her "hold" rating, too, calling the European action "incrementally positive, implying ongoing FDA concerns may be less threatening," but pointing out that overseas approval "does not necessarily represent a good proxy for predicting FDA outlook." Chao expects Encysive to hear from the FDA later this month.
Thelin would go up against Allschwil, Switzerland-based Actelion Ltd.'s Tracleer (bosentan), the only approved endothelin agonist for PAH, which won clearance in Europe four years ago and was cleared in the U.S. in November 2001.
Fein called the EU "highly price sensitive." Though Encysive seems willing to price below Tracleer, "we believe the impact on revenues will be small," he wrote in a research report. Fein estimated Tracleer sells about $200 million per year in Europe.
Also in the PAH game is Denver-based Myogen Inc., with Phase III ambrisentan, described as a non-sulfonamide, propanoic acid-class, type-A selective endothelin receptor antagonist. Top-line data of ambrisentan disclosed in December showed the drug improved patients' exercise capacity, as well as a key secondary endpoint of time to clinical worsening. (See BioWorld Today, Dec. 13, 2005.)
Others to make news in PAH recently include CoTherix Inc., of South San Francisco, which started a Phase III trial of Ventavis (iloprost) inhalation solution in combination with sildenafil citrate. Called VISION (Ventavis Inhalation with Sildenafil to Improve and Optimize Pulmonary Arterial Hypertension), the study involves 180 patients who will be randomized to one of three treatment groups for 16 weeks. The primary clinical endpoint is an increase in the distance walked in six minutes.
Ventavis is CoTherix's prostacyclin, cleared for PAH at the end of 2004. United Therapeutics Inc., of Silver Springs, Md., has another prostacyclin, Remodulin (treprostinil), granted approval in the U.S. in May 2002.
A year ago, New York-based Pfizer Inc. won approval for Revatio, its lower-dose form of sildenafil citrate (the active ingredient in the erectile-dysfunction drug Viagra) for PAH. (See BioWorld Today, June 7, 2005.)
More Recommendations
Also gaining a positive nod from the European panel was Framingham, Mass.-based GTC Biotherapeutics Inc.'s recombinant antithrombin ATryn, and Copenhagen, Denmark-based TopoTarget A/S' topoisomerase II inhibitor, Savene.
Members recommended ATryn for the prophylaxis of thromboembolism in surgery on patients with congenital antithrombin deficiency. GTC's stock (NASDAQ:GTCB) soared nearly 85 percent on the news, closing Friday at $1.81, up 83 cents.
Savene (dexrazoxane) is designed to be given intravenously as an antidote when anthracyclines accidentally are infused outside the vein and into surrounding tissue. In April, the FDA granted priority review for the product in the U.S., where it is branded Totect.
On the pharma side, F. Hoffmann-La Roche Ltd., of Basel, Switzerland, said it received a recommendation for approval of MabThera (rituximab) from the Committee for Medicinal Products for Human Use for the treatment of rheumatoid arthritis in Europe. MabThera, a B-cell therapy, previously was approved in the U.S. under the brand name Rituxan, and marketed by South San Francisco-based Genentech Inc. and Cambridge, Mass.-based Biogen Idec Inc.
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