Tracleer and PPH News Public 'Defenseless' Vs. Bad Drugs U.S. Drug Safety Reviewer at Vioxx Hearing Says the Public Is 'Virtually Defenseless' Against Bad Drugs
WASHINGTON Nov 18, 2004 - The Associated Press— The public is "virtually defenseless" if another medication such as Vioxx proves unsafe after it has won Food and Drug Administration approval, a government drug safety expert said Thursday. "I would argue that the FDA as currently configured is incapable of protecting America against another Vioxx," said David Graham, who warned that the arthritis drug had been linked to an increased risk of heart attack and stroke. He told the Senate Finance Committee there were at least five other drugs on the market that warrant scrutiny: the acne drug Accutane, the weight loss drug Meridia, the anti-cholesterol drug Crestor, the pain reliever Bextra, and the asthma drug Serevent. AstraZeneca PLC, maker of Crestor, said it was confident the drug was safe. "To date, the FDA has not given us any indication of a major concern regarding Crestor," spokeswoman Emily Denney said. Carolyn Glynn, spokeswoman for Roche Holdings AG, a manufacturer of Accutane, noted the drug is intended for serious cases and does carry risks. "This drug is extremely beneficial as long as its used safely and appropriately," she said. GlaxoSmithKline, which makes Serevent, said the medication is safe and effective "when used appropriately and in accordance with labeling and treatment guidelines." Representatives of Pfizer, the manufacturer of Bextra, were not immediately available Thursday. A second FDA official, Dr. Sandra Kweder of the office of new drugs, did not agree with Graham's assessment of the risk posed by the five drugs. She said "there is no magic formula" to determine which drugs most raise the most serious safety concerns. Vioxx's maker, Merck & Co. pulled the drug from the market on Sept. 30 after a study indicated the popular painkiller doubled the risk of heart attacks and stroke when taken for longer than 18 months. Raymond V. Gilmartin, the company president, said in prepared testimony that Merck acted within four days of learning about the risk. "Withdrawing Vioxx was consistent with an ethic that has driven Merck actions and decisions for more than 100 years," he said. Gilmartin said the company was surprised by the cardiovascular risk because it differed from past clinical trials. "My wife was a user of Vioxx until the day we withdrew it from the marketplace," he said. The FDA has defended its actions regarding Vioxx. In a statement late Wednesday, the agency cited its "well-documented and long-standing commitment to openness and transparency in its review of marketed drugs." But the committee chairman, Sen. Charles Grassley, said an independent board of drug safety might be needed to ensure the safety of medications after they are approved for the market. "Consumers should not have to second-guess the safety of what's in their medicine cabinet," said Grassley, R-Iowa. Graham told the committee that research indicated that Vioxx caused up to 160,000 heart attacks and strokes. He said his research helped persuade the FDA to withdraw a number of drugs, including Fen-phen, a weight loss drug. Yet he also questioned the agency's commitment to removing unsafe drugs from the market because doing so would call into question their earlier approval. Sen. Jeff Bingaman criticized the FDA for a "culture … where the pharmaceutical industry, which the FDA is supposed to regulate, is seen by the FDA as its client instead." He urged President Bush to appoint a new head for the agency, now led by an acting commissioner, Lester Crawford. In the FDA statement, Crawford said the FDA initiated and paid for reviews of Vioxx and antidepressants after those drugs had hit the market. "That is evidence the system is working," Crawford said.
Critics contend the agency ignored risks in both instances, then intimidated its own reviewers when they pointed to safety concerns.
Myogen Announces Completion of Enrollment for Pivotal Phase 3 ARIES-2 Trial of Ambrisentan in PAH
Top Line Results of Trial Expected by Year-End
DENVER, July 21 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG - News), a biopharmaceutical company focused on the discovery, development and commercialization of small molecule therapeutics for the treatment of cardiovascular disorders, today announced the completion of enrollment of 187 patients in ARIES-2, one of the Company's two pivotal Phase 3 trials of ambrisentan in patients with pulmonary arterial hypertension (PAH). The Company expects to report top line results of the trial by the end of this year. In addition, the Company expects to complete patient enrollment in ARIES-1 in the fourth quarter of 2005 and report top line results approximately six months thereafter.
"The completion of patient enrollment in ARIES-2 is an important milestone for ambrisentan and Myogen," said J. William Freytag, President and Chief Executive Officer of Myogen. "We are gratified by the support and confidence of the patients and clinical investigators participating in the ARIES trials. Based on the properties of the compound and the results of our Phase 2 trial, we believe ambrisentan's efficacy and safety profile may position it as the best-in-class among endothelin receptor antagonists. We are excited by the progress of our ambrisentan clinical program and look forward to sharing the results of the ARIES-2 trial later this year."
In January 2004, Myogen initiated 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 and the geographic locations of the investigative sites. Both trials are designed to enroll 186 patients (62 patients per dose group). ARIES-1 evaluates doses of 5.0 milligrams and 10.0 milligrams of ambrisentan administered orally once per day and ARIES-2 evaluates doses of 2.5 milligrams and 5.0 milligrams of ambrisentan administered orally once per day. The primary efficacy endpoint is exercise capacity, measured as the mean change from baseline at 12 weeks in the six-minute walk test compared to placebo. Secondary endpoints include time to clinical worsening, World Health Organization (WHO) Functional Class and Borg Dyspnea Index. ARIES-1 is enrolling patients primarily from North America plus selected international sites, while ARIES-2 enrolled patients primarily in Europe plus selected international sites.
In September 2003, Myogen reported results of a Phase 2 clinical trial of ambrisentan in patients with PAH. Based on those results and results of the associated extension study, Myogen believes ambrisentan's profile may position it as the best-in-class endothelin receptor antagonist with demonstrated:
* Significant improvements in six-minute walk distance, Borg Dyspnea
Index and WHO Functional Class
* Durable efficacy with long-term use and a possible survival benefit
* Comparable efficacy in WHO Functional Class 2 and Class 3 patients
* Selectivity for the endothelin type-A receptor
* Dose flexibility
* True once-daily dosing
* No drug-drug interactions (no p450 induction or inhibition)
* Low incidence and severity of potential liver toxicity that does not
appear to be dose related
About Pulmonary Arterial Hypertension
PAH is a highly debilitating disease of the lungs 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 like scleroderma (an autoimmune disease of the connective tissues), cirrhosis of the liver, congenital heart defects and HIV infection. PAH afflicts approximately 50,000 patients, predominantly women, in the United States.
About Ambrisentan
Ambrisentan is being developed as an 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 type-A selective endothelin receptor antagonist and potent inhibitor of endothelin-induced vasoconstriction. Endothelin is a small peptide hormone that is believed to play 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. Therefore, the Company believes that agents that block the detrimental effects of endothelin may provide significant benefits in the treatment of these conditions.
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 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, 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 www.myogen.com.
Safe Harbor Statement
This press release contains forward-looking statements that involve significant risks and uncertainties, including statements relating to ambrisentan clinical data and the completion and release of results of the Company's ARIES clinical trials. 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.
Among other things, the projected completion of the Company's clinical trials, including the ARIES trials, and the timing of the release of results of clinical trials may be affected by difficulties or delays, including difficulties or delays in patient enrollment, patient treatment, data collection and data analysis. Delays in 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. 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, including the results of the Company's ARIES-1 and ARIES-2 clinical trials. Top line results of a clinical trial may not be confirmed upon full analysis of the detailed results of the trial. If the Company's product candidates, including ambrisentan, 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, 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, have better safety profiles than competing products, including a lower incidence of liver toxicity or liver toxicity that is not dose dependent. Myogen's results may also be affected by competition from other pharmaceutical and biotechnology companies, Myogen's ability to successfully develop and market its current products, regulatory developments involving current and future products and its effectiveness at managing its financial resources. 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 July 21, 2005. 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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Source: Myogen, Inc.
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