Healthcare Industry News: pulmonary arterial hypertension
News Release - February 13, 2006
Myogen Reports Positive Top Line Results for Ambrisentan LFT Rescue Study In Pulmonary Arterial HypertensionPatients with PAH Who Previously Discontinued Other ERA Therapy Due to Liver Function Abnormalities Treated with Long-term Ambrisentan Therapy
DENVER, Feb. 13 (HSMN NewsFeed) -- Myogen, Inc. (Nasdaq: MYOG ) today announced positive top line results of the AMB-222 study, an open-label study of ambrisentan in patients with pulmonary arterial hypertension (PAH) who have previously discontinued bosentan and/or sitaxsentan treatment due to liver function abnormalities. None of the 36 patients enrolled in the study had a recurrence of liver function abnormalities that resulted in discontinuation of ambrisentan during the initial 12-week evaluation period (the primary endpoint of the study). One patient had a transient serum aminotransferase test result greater than three-times the upper limit of the normal range (3xULN) at week 12 that resulted in dose reduction from 5 mg to 2.5 mg ambrisentan. This patient remains on ambrisentan therapy and has not had a recurrence of serum aminotransferases greater than 3xULN. Patients have continued to receive ambrisentan therapy for periods up to 9 months (mean exposure of 6 months) and no further occurrence of serum aminotransferase concentrations greater than 3xULN has been observed.
"These results suggest that for patients who have had to stop treatment with other endothelin receptor antagonists due to liver function abnormalities, ambrisentan may offer an opportunity to resume treatment," stated Michael J. Gerber, MD, Senior Vice President of Clinical Development and Regulatory Affairs for Myogen. "I believe ambrisentan has the potential to be an important therapeutic option for these patients with PAH and their physicians. The low incidence and severity of liver function test abnormalities demonstrated in the ARIES-2 trial and the AMB-222 rescue study are very encouraging. Ambrisentan has a chemical structure that differs from those of bosentan and sitaxsentan. We believe that this distinction may underlie ambrisentan's low propensity to cause liver function abnormalities."
Myogen announced the initiation of AMB-222 in May 2005 with a target enrollment of 30 patients. A total of 36 patients were enrolled in the study, of which 31 (86%) had discontinued bosentan, 2 (6%) had discontinued sitaxsentan and 3 (8%) had discontinued both bosentan and sitaxsentan, sequentially, due to serum aminotransferase abnormalities. Also, 17 (47%) of the patients were receiving concomitant sildenafil therapy. Patients received 2.5 mg of ambrisentan once daily for 4 weeks and then the dose was increased to 5 mg of ambrisentan once daily. The last patient reached the 12-week endpoint evaluation in January 2006. All patients had the option to continue ambrisentan therapy after the initial 12-week assessment period.
The primary endpoint of the trial was the incidence of serum aminotransferase concentrations greater than 3xULN during the 12-week evaluation period that were related to ambrisentan and resulted in discontinuation of drug.
The top line results of the ARIES-2 and AMB-222 trials, as well as the results to date of Myogen's Phase 2 trial of ambrisentan in PAH (AMB-220) and related long-term study (AMB-220-E) 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 for patients with WHO functional class II and 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
* Potential utility in resuming endothelin receptor antagonist (ERA) treatment in patients who have discontinued bosentan or sitaxsentan treatment due to liver function abnormalities
* 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.
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.
Myogen is a biopharmaceutical company focused on the discovery, development and commercialization of small molecule therapeutics for the treatment of cardiovascular disorders. Myogen currently has two product candidates in late-stage clinical development: ambrisentan for the treatment of patients with pulmonary arterial hypertension and darusentan for the treatment of patients with resistant hypertension. The Company 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 www.myogen.com.
Safe Harbor Statement
This press release contains forward-looking statements that involve significant risks and uncertainties, including summary statements relating to the top line results of the Company's AMB-222 clinical trial, summary statements relating to the top line results of the ARIES-2 trial and results of the Company's Phase 2 trial of ambrisentan in patients with PAH and the related extension trial, and summary statements relating to the potential efficacy and safety profile of ambrisentan. Actual results could differ materially from those projected and the Company cautions investors not to place undue reliance on the forward-looking statements contained in this release.
Results from clinical trials, including the Company's AMB-222 trial, are not necessarily predictive of future clinical results, including results of the ARIES-1 trial of ambrisentan in patients with PAH. Top line results may not be confirmed upon full analysis of the detailed results of a trial and additional information relating to the safety, efficacy or tolerability of the Company's product candidates, including ambrisentan, may be discovered upon further analysis of trial data and upon review and analysis of additional trial data, including data from the Company's ongoing ARIES-1 trial and its Phase 2 and Phase 3 extension trials of ambrisentan in patients with PAH. If the Company's product candidates do not meet 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 the Company's product candidates meet safety and efficacy endpoints, regulatory authorities may not approve them, the Company may not be able to successfully market them, or the Company may face post-approval problems that require the withdrawal of its product from the market. There can be no assurance that Myogen's product candidates, including ambrisentan, will be proven safe and effective for use in humans. Abnormal elevations of liver function test results, including elevated serum aminotransferase concentrations, have been reported in trials of other endothelin receptor antagonists. The Company's results may be affected by its effectiveness at managing its financial resources, its ability to successfully develop and market its product candidates, its ability to obtain and enforce patent protection for its products, competition from other biotechnology and pharmaceutical companies, difficulties or delays in manufacturing its products, and regulatory developments involving current and future products. Delays in initiating or conducting clinical trials, whether caused by competition, adverse events, patient enrollment rates, regulatory issues or other factors, could adversely affect the Company's financial position and prospects. 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 reports on Form 10-Q and Form 8- K. It is Myogen's policy to only update or reconfirm its public guidance by issuing a press release or filing a periodic or current report with the Securities and Exchange Commission. The Company generally plans to provide guidance as part of its annual and quarterly earnings releases but reserves the right to provide guidance at different intervals or to revise its practice in future periods. All information in this press release is as of February 13, 2006. Myogen undertakes no duty or obligation to update any forward- looking statements contained in this release as a result of new information, future events or changes in the Company's expectations. The Company also disclaims any duty to comment upon or correct information that may be contained in reports published by the investment community.
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