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Myogen Reports Positive Top Line Results for Ambrisentan Phase 3 Trial in Pulmonary Arterial Hypertension

http://biz.yahoo.com/prnews/051212/nym114.html?.v=35

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Monday December 12, 7:30 am ET

Significant Improvement in Six-Minute Walk Distance of 59.4 Meters and in Time to Clinical Worsening with No Observed Liver Function Abnormalities

DENVER, Dec. 12 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG ) today announced positive top line results of the ARIES-2 trial, the first pivotal Phase 3 trial evaluating ambrisentan, an oral endothelin receptor antagonist (ERA), in pulmonary arterial hypertension (PAH). The trial met the primary efficacy endpoint of improved exercise capacity, the key secondary endpoint of time to clinical worsening and several other secondary efficacy endpoints.

The primary efficacy endpoint of the ARIES-2 trial was the placebo-corrected mean change in six-minute walk distance (6MWD) at week 12 compared to baseline. Results of the trial demonstrated that with once-daily dosing, 5 mg of ambrisentan improved the placebo-corrected mean 6MWD by 59.4 meters (p=0.0002) and 2.5 mg of ambrisentan improved the placebo-corrected mean 6MWD by 32.3 meters (p=0.0219). For the placebo group, the mean 6MWD at week 12 decreased from baseline by 10.1 meters. Improvements in time to clinical worsening compared to placebo were observed for both the 5 mg dose group (p=0.0076) and the 2.5 mg dose group (p=0.0048).

The trial safety results demonstrated ambrisentan was generally well tolerated. The most frequent adverse event was headache, which occurred in 12.7% of patients in the 5 mg dose group and 7.8% in the 2.5 mg dose group, compared to 6.2% in the placebo group. No patients treated with ambrisentan developed serum aminotransferase concentrations greater than three-times the upper limit of the normal range, compared to one patient in the placebo group. Ambrisentan had no apparent effect on the activity or dosage of warfarin-type anticoagulants commonly prescribed for patients with PAH.

"We believe the robustness of these results is unprecedented for oral therapies for patients with pulmonary arterial hypertension and represents a significant achievement for ambrisentan and Myogen," said J. William Freytag, President and Chief Executive Officer of Myogen. "We greatly appreciate the support and efforts of the ARIES-2 clinical sites. Based on the properties of ambrisentan and the clinical results obtained to date, we believe that, if approved, ambrisentan has the potential to offer significant advantages over other endothelin receptor antagonists for the treatment of PAH. We are excited by the progress of the ambrisentan clinical program and look forward to learning the results of ARIES-1 in the second quarter of 2006."

"The top line results of this trial fulfilled our expectations in every regard," said Dr. Michael Gerber, Senior Vice President of Clinical Development and Regulatory Affairs for Myogen. "The magnitude of improvement in six-minute walk distance and dose-response for the primary endpoint were impressive. Furthermore, the delay in clinical worsening observed at week 12 for both dose groups compared to placebo was remarkable. These results and those of our long-term Phase 2 trial suggest that, if approved, ambrisentan could ultimately represent a major treatment advance for patients with pulmonary arterial hypertension."

In January 2004, Myogen announced the initiation of two pivotal Phase 3 clinical trials, ARIES-1 and ARIES-2, evaluating the safety and efficacy of ambrisentan in patients with PAH. The ARIES trials are randomized, double-blind, placebo-controlled trials of identical design except for the doses of ambrisentan studied and the geographic locations of the investigative sites. Both trials were designed to enroll 186 patients (62 patients per dose group). ARIES-1 will evaluate once-daily doses of 5 mg and 10 mg of ambrisentan. ARIES-2 evaluated once-daily doses of 2.5 mg and 5 mg of ambrisentan. The primary efficacy endpoint is exercise capacity, measured as the mean change from baseline at 12 weeks in the 6MWD compared to placebo. Secondary endpoints include time to clinical worsening, World Health Organization (WHO) functional class, SF-36(TM) Health Survey, and Borg dyspnea index. ARIES-2 enrolled 192 patients primarily from Europe, while ARIES-1 enrolled 202 patients primarily from the United States. The Company expects to report top line results for ARIES-1 in the second quarter of 2006.

In addition, more than 300 patients continue ambrisentan treatment in long-term trials with maximum exposure of more than three years.

The top line results of the ARIES-2 trial and the results to date of Myogen's Phase 2 trial of ambrisentan in PAH and related long-term study have demonstrated:

- Improvement in exercise capacity that is significant, early in onset and durable

- Significant improvement in time to clinical worsening

- Comparable benefit in exercise capacity in patients with WHO functional class II symptoms relative to those with class III symptoms

- An apparent survival benefit when compared with predicted survival based on the National Institutes of Health Registry formula

- Effectiveness with once-daily dosing and the potential for dose flexibility

- Low incidence and severity of liver function test abnormalities at all doses

- No apparent drug-drug interactions with warfarin-type anticoagulants

Based on results to date and the properties of ambrisentan, Myogen believes that, if ambrisentan is ultimately approved, it may offer significant clinical benefit to PAH patients not provided by other PAH therapies.

About Pulmonary Arterial Hypertension

PAH is a highly debilitating disease characterized by severe constriction of the blood vessels in the lungs leading to very high pulmonary arterial pressures. These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated. Patients with PAH suffer from extreme shortness of breath as the heart struggles to pump against these high pressures causing such patients to ultimately die of heart failure. PAH can occur with no known underlying cause, or it can occur secondary to diseases such as connective tissue disease, congenital heart defects, cirrhosis of the liver and HIV infection. PAH afflicts approximately 200,000 patients worldwide.

About Ambrisentan

Ambrisentan is an investigational drug being developed as a once daily oral therapy for patients with PAH and has been granted orphan drug designation for the treatment of PAH in both the United States and European Union.

Ambrisentan is a non-sulfonamide, propanoic acid-class, type-A selective endothelin receptor antagonist. Endothelin is a small peptide hormone that plays a critical role in the control of blood flow and cell growth. Elevated endothelin blood levels are associated with several cardiovascular disease conditions, including pulmonary arterial hypertension, chronic renal disease, coronary artery disease, hypertension and chronic heart failure. The Company believes that agents that block the detrimental effects of endothelin may provide significant benefits in the treatment of these conditions.

Conference Call

J. William Freytag, President and CEO, and other members of Myogen's senior management will discuss the ARIES-2 top line results via webcast and conference call on Monday, December 12, 2005 at 8:30 am Eastern. To access the live webcast, please log on to the Company's website at http://www.myogen.com and go to the Investor Relations section. Alternatively, callers may participate in the conference call by dialing 800-366-3908 (domestic) or 011-1-303-262-2140 (international). Webcast and telephone replays of the conference call will be available approximately two hours after the completion of the call through Friday, December 30, 2005. Callers can access the replay by dialing 800-405-2236 (domestic) or 011-1-303-590-3000 (international). The passcode is 11048390#.
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