Study: Identical Doses of BiDil Components Are Not Bioequivalent to the Fixed Dose Combination-BiDil-Used in A-HeFTNEW ORLEANS, La.--(BUSINESS WIRE)--Mar 26, 2007 - A study comparing the formulations of isosorbide dinitrate (ISDN) and hydralazine (HYD) used in V-HeFT I and V-HeFT II, and BiDil, the proprietary fixed dose combination, used in the African American Heart Failure Trial (A-HeFT) demonstrated no bioequivalence. Non-bioequivalence in the formulations used may explain why V-HeFT I and V-HeFT II showed very different results in decreasing mortality. Using identical amounts of active drugs, the two formulations of ISDN and HYD were not bioequivalent to each other and neither were bioequivalent to BiDil, according to FDA requirements. The study results are being presented today in New Orleans at the American College of Cardiology's 56th Annual Scientific Session.
"This analysis is significant because it provides invaluable insight into the treatment of heart failure in black patients who suffer disproportionately compared to their white counterparts," said Milton Packer, M.D. a heart failure specialist and co-author of the study from the University of Texas, Southwestern Medical Center in Dallas. "Two large heart failure studies using two distinct formulations showed different results in decreasing mortality, only BiDil has shown significant reductions in death and hospitalization in black heart failure patients, as seen in A-HeFT. No drugs have been shown to be therapeutically equivalent to or substitutable for BiDil. Unproven remedies should not be used in a disease state where 50% of the patients will die within 5 years, and 50% of severe HF patients will die within one year," he said.
BiDil was approved in June 2005 by the U.S. Food and Drug Administration and is indicated for the treatment of heart failure as an adjunct to current standard therapy in self-identified black patients, to improve survival, prolong time to hospitalization for heart failure and improve patient-reported functional status. There is little experience in patients with New York Heart Association (NYHA) class IV heart failure. Most patients in the clinical trial supporting effectiveness, referred to as A-HeFT, received, in addition to BiDil or placebo, a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist.
In A-HeFT, self-identified black patients taking BiDil in addition to current standard heart failure therapies (n=518) experienced a significant 43 percent decrease in the risk of mortality (P=.012) (absolute mortality rate: BiDil, 6.2 percent vs. placebo, 10.2 percent), a 39 percent reduction in the risk of first hospitalization for heart failure (P less than .001) (absolute first hospitalization rate: BiDil, 16.4 percent vs. placebo, 24.4 percent) and a statistically significant improvement at most time points in response to the Minnesota Living with Heart Failure Questionnaire, which is a self-report of the patient's functional status, versus patients taking placebo (n=532) in addition to current standard therapies.
Heart Failure Burden in Black Patients
Heart failure, or end-stage cardiovascular disease, affects approximately five million Americans, including an estimated 750,000 African Americans. Each year, over 550,000 people are diagnosed with heart failure for the first time, and there is no cure for this disease - with more than 50 percent of patients dying within five years of diagnosis. With respect to heart failure, blacks are affected at a rate greater than that of the corresponding non-black population, presenting with the disease earlier and dying sooner. According to the Centers for Disease Control and Prevention (CDC), African Americans between the ages of 45 and 64 are 2.5 times more likely to die from heart failure than Caucasians in the same age range.
Important Safety Information
BiDil is contraindicated in patients who are allergic to organic nitrates. Augmentation of the vasodilatory effects of isosorbide dinitrate by phosphodiesterase inhibitors (e.g., Viagra((R))/Revatio(TM), Levitra((R)), Cialis((R))) could result in severe hypotension.
Treatment with hydralazine may produce a clinical picture simulating systemic lupus erythematosus (SLE) including glomerulonephritis. If SLE-like symptoms occur, discontinuation of BiDil should be considered. Residua have been detected many years after discontinuation of hydralazine. Symptomatic hypotension may occur with even small doses of BiDil. BiDil should be used with caution in volume depleted or hypotensive patients. Hydralazine can cause tachycardia potentially leading to myocardial ischemia and anginal attacks. Careful clinical and hemodynamic monitoring is recommended when BiDil is administered to patients with acute myocardial infarction to avoid hypotension and tachycardia. Isosorbide dinitrate therapy may aggravate angina associated with hypertrophic cardiomyopathy.
Hydralazine hydrochloride has been associated with peripheral neuritis, evidenced by paresthesia, numbness and tingling, which may be related to an antipyridoxine effect. Caution should be exercised if BiDil is used with MAO inhibitors, alcohol, sildenafil, vardenafil or tadalafil.
Headache (50 percent) and dizziness (32 percent) were the two most frequent adverse events and were more than twice as frequent in the BiDil group.
Viagra is a registered trademark and Revatio is a trademark of Pfizer, Inc.; Levitra is a registered trademark of Bayer HealthCare, GlaxoSmithKline, and Schering-Plough; Cialis is a registered trademark of Lilly ICOS LLC.
About NitroMed, Inc.
NitroMed of Lexington, Massachusetts is a research-based emerging pharmaceutical company and the maker of BiDil, an orally administered medicine available in the United States for the treatment of heart failure in self-identified black patients. In this population, BiDil is indicated as an adjunct to current standard therapies such as ACE inhibitors and/or beta blockers. BiDil was approved in June 2005 by the U.S. Food and Drug Administration, primarily on the basis of efficacy data from the Company's landmark A-HeFT (African American Heart Failure Trial) clinical trial, and since July 2005, has been marketed by NitroMed.
The Company is committed to the development of novel pharmaceuticals and safer, more effective versions of existing drugs to treat underserved patient populations. NitroMed's development efforts are primarily directed at expanding its cardiovascular franchise.
Forward Looking Statements
Statements in this press release about future expectations, plans and prospects for the Company, including the Company's expectations regarding the effect of its operational restructurings, its expectations regarding cash management and operating expenses in 2007, its positioning to achieve the Company's goals and objectives in 2007, and its plans to increase value for the Company and its stockholders, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: difficulties in successfully developing, obtaining regulatory approval for, manufacturing and commercializing BiDil XR(TM), including the Company's ability to maintain third-party relationships for the development and manufacture of clinical and commercial quantities of BiDil XR(TM) on favorable terms, if at all; the Company's ability to execute on its revised sales and marketing strategy including without limitation, the Company's inability to achieve anticipated cost reductions, the Company's ability to successfully market and increase the sales of BiDil with limited sales force support and centralized marketing efforts, the Company's ability to recruit the specialized sales representatives necessary to execute on this strategy, and the Company's ability to successfully enter into a co-promotion agreement for BiDil on favorable terms, if at all; the Company's ability to enter into collaboration or licensing arrangements with strategic partners related to its product candidate portfolio on favorable terms, if at all; the Company's ability to obtain the substantial additional funding required to conduct manufacturing, marketing and sales of BiDil and to develop, conduct clinical trials for and, if approved, commercialize BiDil XR(TM); patient, physician and third-party payer acceptance of BiDil and/or BiDil XR(TM) as a safe and effective therapeutic; the Company's ability to obtain or maintain intellectual property protection and required licenses; unanticipated operating expenses for the remainder of fiscal year 2007 and beyond; and other important factors discussed in the Section titled "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2006, which has been filed with the SEC. The forward-looking statements included in this press release represent the Company's views as of the date of this release. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this release.
Jane A. Kramer, 781-266-4220
Posted: March 2007