Tracleer and PPH News TRACLEER WILL NOT EXPAND INTO TREATMENT OF CONGESTIVE HEART FAILURE Actelion (Swiss: ATLN) and Genentech's (NYSE: DNA) Tracleer (bosentan) has failed to meet primary endpoints of the phase III ENABLE trial. Tracleer failed both to reduce time to death or hospitalization due to congestive heart failure, and to improve clinical status at nine months of treatment. ENABLE was assessing the novel endothelin receptor antagonist in 1,613 patients with severe chronic congestive heart failure (CHF NYHA Class IIIb/IV).
Tracleer's safety and tolerability profile remained reassuring throughout the trial, which support its continued use in its approved indication - pulmonary arterial hypertension (PAH). Data from the trial, including subgroup analyses, will be presented at the American College of Cardiology meeting, March 17-21, in Atlanta. In late November, the FDA approved Tracleer for the treatment of PAH. The drug is indicated to improve exercise ability and decrease the rate of clinical worsening in PAH patients with significant limitation of physical activity. Tracleer is the first approved oral treatment for PAH patients. In the past, PAH patients have needed to wear a battery-powered pump that infuses prostacyclin through a permanently implanted tube in the chest. Adverse effects of Tracleer may include liver damage and birth defects, and patients require monthly blood tests to catch early signs of liver damage. Female patients need monthly pregnancy tests. Tracleer is not sold in general drugstores; Actelion has hired 4 specialty pharmacies to distribute the drug to patients once their physicians enroll them in the Tracleer access program. The drug costs approximately $28,500 a year, far less than today's intravenous prostacyclin therapy that costs about $60,000 annually.
Pulmonary hypertension, in its primary form, strikes one or two people per million. Secondary forms, such as a rare adverse effect of the now-banned diet pills Redux and fen-phen, and as a complication of lupus and other rheumatologic disorders, are more frequent.
Pulmonary hypertension is high blood pressure in the pulmonary (lung and related) arteries and/or its branches, blood vessels normally under considerably lower pressures than those of the aorta and its branches that go to the rest of the body. Pulmonary hypertension can lead to irreparable and devastating lung damage.
Viagra Ingredient Helps Blood Pressure Disorder
-- Scott Roberts
WEDNESDAY, June 8 (HealthDay News) -- The active ingredient in the erectile dysfunction drug Viagra has been approved by the U.S. Food and Drug Administration to treat a dangerous form of high blood pressure called pulmonary hypertension.
The new drug, to be called Revatio, contains sildenafil, the ingredient that relaxes blood vessels among users of Viagra. The 20 mg. dose of Revatio, to be taken three times daily, is cumulatively higher than the daily formulation for Viagra, the Associated Press reported.
Pulmonary hypertension, though rare, can destroy the heart. Another oral treatment, Tracleer, was approved in 2001.
In clinical trials, people who took Revatio reported side effects similar to those of Viagra, including headache and flushing.
The Revatio approval came on the heels of last week's reports that the FDA is investigating whether Viagra and similar impotence drugs may contribute to a rare form of blindness.
For more information about pulmonary hypertension, visit the Pulmonary Hypertension Association.
Myogen Initiates Trial of Ambrisentan in Patients Who Previously Failed Other ERA Therapy
DENVER, May 19 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG), a biopharmaceutical company focused on the discovery, development and
commercialization of small molecule therapeutics for the treatment of
cardiovascular disorders, today announced the initiation of a clinical trial
to evaluate ambrisentan in patients with pulmonary arterial hypertension (PAH) who have previously discontinued bosentan or sitaxsentan therapy due to liver function test (LFT) abnormalities, specifically elevated serum
aminotransferase concentrations.
The primary objective of this trial is to determine the incidence of
increased serum aminotransferase concentrations associated with ambrisentan therapy in patients who have previously discontinued bosentan or sitaxsentan therapy due to serum aminotransferase abnormalities. This trial will also evaluate the overall safety, tolerability and efficacy of ambrisentan in this patient population. Approximately 30 patients will receive 2.5 mg ambrisentan daily for 4 weeks followed by 5 mg of ambrisentan daily. Patients will be monitored with clinical laboratory tests every 2 weeks and assessed for safety and efficacy every 4 weeks during the first 12 weeks of treatment. The primary endpoint will be assessed after the first 12 weeks of treatment. Patients who complete week-48 in the extended portion of the study have the option to receive 10 mg of ambrisentan daily.
Previous clinical trials with bosentan (BREATHE-1) and sitaxsentan
(STRIDE-1) have demonstrated dose-dependent increases in serum
aminotransferase concentrations, specifically alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) concentrations, requiring withdrawal of therapy for reasons of safety. Preclinical studies suggest that serum aminotransferase elevations induced by bosentan and chemically-related compounds may be due to their direct competition with bile salts for active transport across the hepatocyte membrane into the bile canaliculi.
We believe an endothelin receptor antagonist (ERA) such as ambrisentan that has a distinctly different chemical composition and metabolic pathway may result in less competition with endogenous bile salts for canalicular transport. In addition, ambrisentan demonstrated significant efficacy when administered at daily doses of 1 to 10 mg, doses that are 10-250 times lower than the approved daily dose of bosentan (125 mg bid) and the proposed daily dose of sitaxsentan (100 mg once daily). We believe these lower doses might introduce less competition on a molar basis for canalicular transport, which could result in a lower incidence and severity of serum aminotransferase elevations.
About Ambrisentan
Ambrisentan is an ETA selective endothelin receptor antagonist being
developed as an oral therapy for patients with PAH. Ambrisentan has been
granted orphan drug designation for the treatment of PAH in both the United States and European Union. The Company completed a Phase 2 clinical trial of ambrisentan in September 2003.
In January 2004, Myogen initiated two pivotal Phase 3 clinical trials,
ARIES-1 & ARIES-2, for ambrisentan in PAH. The ARIES trials are randomized, double-blind, placebo-controlled trials of identical design except for the doses of ambrisentan and the geographic locations of the investigative sites.
The study design anticipates enrolling 186 patients (62 patients per dose
group) in each trial. ARIES-1 will evaluate ambrisentan doses of 5.0
milligrams and 10.0 milligrams administered orally once per day for 12 weeks.
ARIES-2 will evaluate ambrisentan doses of 2.5 milligrams and 5.0 milligrams administered orally once per day for 12 weeks. The primary efficacy endpoint is exercise capacity, measured as the change from baseline in the six-minute walk test distance compared to placebo. Secondary endpoints include Borg Dyspnea Index, World Health Organization (WHO) Functional Class and time to clinical worsening. ARIES-1 is being conducted both in the United States and abroad, while ARIES 2 is being conducted outside of the United States. The Company expects to complete enrollment in ARIES-2 by the end of June 2005 and ARIES-1 in the fourth quarter of 2005. The Company plans to report preliminary results from each study approximately six months following the completion of enrollment in that trial.
About Myogen
Myogen is a biopharmaceutical company focused on the discovery,
development and commercialization of small molecule therapeutics for the
treatment of cardiovascular disorders. Myogen currently markets one product in Europe for the treatment of acute decompensated heart failure and has three product candidates in late-stage clinical development: enoximone capsules for the treatment of patients with chronic heart failure, ambrisentan for the treatment of patients with pulmonary arterial hypertension and darusentan for the treatment of patients with resistant hypertension. The Company, in collaboration with Novartis, also conducts a target and drug discovery research program focused on the development of disease-modifying drugs for the treatment of chronic heart failure and related cardiovascular disorders. Please visit Myogen's website at http://www.myogen.com.
Safe Harbor Statement
This press release contains forward-looking statements that involve
significant risks and uncertainties, including the statements relating to the
potential of ambrisentan as a treatment for PAH and its effect in patients who have experienced elevated LFTs while taking other therapies. Actual results could differ materially from those projected and Myogen cautions investors not to place undue reliance on the forward-looking statements contained in this release.
The results of Myogen's prior clinical trials of its product candidates,
including ambrisentan, do not necessarily predict the results of later-stage
clinical trials. Preliminary results may not be confirmed upon full analysis
of the detailed results of a trial. There can be no assurance that Myogen's
product candidates, including ambrisentan, have better safety profiles than competing products, including a lower incidence of liver toxicity or liver toxicity that is not dose dependent. Among other things, Myogen's results may be affected by competition from other pharmaceutical and biotechnology companies, Myogen's ability to successfully develop and market its current products, difficulties or delays in its clinical trials, regulatory developments involving current and future products and its effectiveness at managing its financial resources.
If the Company's product candidates, including ambrisentan, darusentan, and enoximone, do not meet the safety or efficacy endpoints in clinical evaluations, they will not receive regulatory approval and the Company will not be able to market them. Even if Myogen's product candidates meet safety and efficacy endpoints, regulatory authorities may not approve them, or the Company may face post-approval problems that require the withdrawal of its products from the market. If the Company is unable to raise additional capital when required or on acceptable terms, it may have to significantly delay, scale back or discontinue one or more of its drug development or discovery research programs. Myogen is at an early stage of development and may not ever have any products that generate significant revenue.
Additional risks and uncertainties relating to the company and its
business can be found in the "Risk Factors" section of Myogen's Form 10-K for the year ended December 31, 2004 and Myogen's periodic reports on Form 10-Q and Form 8-K. Myogen is providing the information contained in this release as of the date of the release and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.
SOURCE Myogen, Inc.
Web Site: http://www.myogen.com
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