ALLSCHWIL and BASEL, Switzerland, Sept. 12, 2002 (PRIMEZONE) -- Actelion Ltd. today announced initial positive results from a dose-optimization study evaluating Veletri(TM) (tezosentan), an intravenous dual endothelin receptor antagonist, in patients suffering from acute heart failure (AHF). Important hemodynamic effects were achieved at doses of 5 mg/h and 25 mg/h. The primary endpoint of the study, improvement of cardiac index, was statistically significant for both doses. Effects of similar magnitude were also achieved in terms of reduction of pulmonary capillary wedge pressure (PCWP), another important hemodynamic parameter. At these doses, the drug was also well tolerated.
Isaac Kobrin, MD, head of clinical development, commented: "I am very pleased with these results. Low doses of Veletri(TM) achieved significant improvements in hemodynamic parameters and, even more importantly, these improvements were achieved with good tolerability and very few vasodilatory side effects."
Based on these results and taking into consideration the need for an AHF drug providing more than symptomatic relief, Actelion has decided to proceed with a registration study (Phase III) with Veletri(TM), evaluating mortality/morbidity benefits.
Final decisions on the trial design will be made following full data analysis and modeling as well as discussions with clinical experts and regulatory authorities worldwide. With preparations already substantially advanced and the results of the dose-optimization trial slightly ahead of schedule, the registration study is expected to be initiated by year-end and last between 18 and 24 months.
Substantial need for new AHF therapies
JeanPaul Clozel, MD, Chief Executive Officer, commented: "With Veletri(TM), Actelion has the unique opportunity to bring to the AHF patients and physicians a drug potentially providing important clinical benefit. Veletri(TM) has demonstrated unique properties, such as significantly improving cardiac index while decreasing PCPW, without affecting heart rate."
JeanPaul Clozel concluded: "With these hemodynamic benefits and good tolerability observed in this dose-optimization study, we expect that patients could benefit from treatment with Veletri(TM). We are hopeful that these benefits may eventually be seen in terms of morbidity/mortality, an effect not previously observed with other treatments for acute heart failure."
Doseoptimization trial design
The dose-optimization study with Veletri(TM) (tezosentan) was a randomized, double blind, placebo-controlled, multi-center, parallel design trial of 129 patients hospitalized for Acute Heart Failure (AHF). Patients were randomized to receive either tezosentan (0.2, 1, 5 or 25 mg/hr) or placebo in addition to standard therapy. Patients were treated for 24 hours and were monitored for 30 days. Both hemodynamic and clinical parameters were evaluated in this trial, with the primary end-point defined as change from baseline cardiac index at 6 hours after drug initiation. Data from this trial was submitted for presentation at an upcoming scientific meeting in 2003.
The doseoptimization trial was undertaken, following detailed analysis of the earlier studies in the RITZ-program. In these trials, treatment with much higher doses of tezosentan (50 and 100mg/h) resulted in hemodynamic benefits, but with concomitant increases of problematic vasodilatory side effects such as hypotension and headache.
Acute Heart Failure - A Leading Cause of Hospitalization Worldwide
AHF is a life-threatening condition in which the ability of the heart to pump enough blood to meet the body's metabolic needs is rapidly and seriously impaired. Each year, nearly one million people in the U.S. are hospitalized with AHF. Patients suffering from AHF typically experience symptoms such as dyspnea, edema, and fatigue, and often present with signs of poor blood flow.
In some cases, the onset of AHF is abrupt, with rapid fluid build-up in the lungs (pulmonary edema), which can impair breathing so drastically that the patient requires intubation and a ventilator for assisted breathing. In other cases, AHF can lead to cardiogenic shock, an abrupt disruption of blood flow that can follow a massive heart attack or surgery.
Actelion signed a U.S. co-promotion agreement for tezosentan with Genentech, Inc. in February 2000, with Actelion taking the lead in developing the drug. Following a successful conclusion of the Phase III program with Veletri(TM) in acute heart failure, Genentech can optin to become a co-promotion partner for Veletri(TM) in the United States.
Invitation to InvestorConference Call / Webcast
Dear Friend in the Investment Community
Actelion Ltd. announced today initial and positive results from a dose-optimization study evaluating Veletri(TM) (tezosentan), an intravenous dual endothelin receptor antagonist, in patients suffering from acute heart failure (AHF).
Actelion will host an Investor Conference Call / Webcast to discuss the results as follows:
Date/Time:
Thursday, 12 September 2002, 15.30hrs (CET) / 09.30 a.m. (EST)
Conference Call Connect #:
Dialin participants should start calling the number below 10-15 minutesbefore the Conference is due to start.
-- European participants should dial 41 (0)91 610 41 11 -- U.S. participants should dial 1 412 858 46 00
Participant's mode:
Listen-Only, with possibility to open individual lines during Q&A session. Participants will be asked for their Name and Company.
Webcast Access:
Webcast participants should visit the Actelion Website www.actelion.com for further details 10-15 minutes before the conference is due to start.
Participant's mode:
Listen-Only, with possibility to ask individual questions by clicking on the Q&A button. Questions will be answered after the call itself is over. Participants will be asked to provide their Name and Company.
Webcast Replay:
The archived Investor Webcast will be available for replay through www.actelion.com approximately 60 minutes after the call has ended.
Calendar update:
September 17
Bear Stearns Healthcare Conference, New York, Webcast: 44:30 EST (10-10:30 CET); Speaker: CFO A. Mueller September 18 Goldman Sachs Global Biotech Conference, Munich October 2 CSFB Eurobiotech Conference, London October 7 UBS Warburg Global Life Sciences Conference November 5 Q3 Results Date Changed no longer November 7 November 14 SG Cowen Health Care Conference, Paris
These dates are scheduled, but may be affected by factors beyond our control.
Actelion Ltd.
Actelion Ltd. is a biopharmaceutical company, with its corporate headquarter in Allschwil/Basel, Switzerland. Actelion's first drug Tracleer(TM), an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer(TM) through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union as well as Canada 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).