Healthcare Industry News: Bayer HealthCare
News Release - March 14, 2006
African American Heart Failure Trial Shows Women and Men Both Benefit from BiDil(R)Females Represent Unprecedented 40 Percent of Patients in Trial
Additional Data Shows BiDil Efficacy in Black Patients Not Limited by Severity of LV Ejection Fraction
ATLANTA--(HSMN NewsFeed)--March 14, 2006--Today, NitroMed, Inc. (NASDAQ:NTMD ) announced the results of a post-approval analysis of the African American Heart Failure Trial (A-HeFT) by gender, which demonstrated similar positive clinical outcomes for both black men and black women taking BiDil® (isosorbide dinitrate/hydralazine hydrochloride) in addition to standard heart failure therapy. This gender comparison was made possible by the unprecedented participation of black women in A-HeFT, in which a record 40 percent of participants were female. In a separate post-approval analysis of A-HeFT results, BiDil was shown to be effective in black heart failure patients regardless of the severity of left ventricular (LV) remodeling, a measurement of decline in heart function. Both sets of study results are being presented today in Atlanta at the American College of Cardiology's 55th Annual Scientific Session.
"These two analyses are significant as data from A-HeFT continue to provide invaluable insight into the treatment of heart failure in black patients," said Michael L. Sabolinski, M.D., Chief Medical Officer, NitroMed. "Through examination of this data, we have learned that BiDil has improved patient outcomes regardless of gender and that BiDil was effective for black patients with various degrees of left ventricular remodeling."
Outcomes by Gender in the African American Heart Failure Trial (Presentation #837-8)
A-HeFT is a landmark study not only because it was the first conducted in a heart failure population in which all of the participants identified themselves as black, but women represented almost half of the patient population studied. This unparalleled female representation in A-HeFT allowed researchers, for the first time, to determine if gender may play a role in heart failure medication response.
Gender analysis to drug response is critical because, despite the fact that women account for nearly 50 percent of all hospital admissions for heart failure, on average only 20 percent of heart failure study participants are women. Consequently, there has been more limited understanding of the potential gender differences in heart medication response.
Data from A-HeFT demonstrated that both men (n=290) and women (n=228) treated with BiDil experienced improved clinical outcomes for heart failure. All-cause mortality appeared to be lower in women than in men treated with BiDil, however, there was no significant difference in the benefit of BiDil on survival between men and women. The magnitude of improvement with BiDil was similar for both men and women, based on the primary composite score consisting of mortality, first heart failure hospitalizations and change in functional status at six months. Time to first heart failure hospitalizations and event-free survival were also similarly improved in men and women.
"Studying the effects of BiDil on black patients by sex offers us tremendous insight into two traditionally underrepresented segments of the heart failure population," said Anne L. Taylor, M.D., Professor of Cardiology at the University of Minnesota in Minneapolis and Chair of the A-HeFT Steering Committee. "Understanding the effects of heart failure treatment in women could translate into fewer deaths and opportunities for continued research."
Characteristics and outcomes by gender and treatment group were compared between men and women at baseline. Patients in A-HeFT received either BiDil or placebo, in addition to current standard heart failure treatment. At baseline, the women in the trial were generally less healthy than men, demonstrating slightly lower hemoglobin, creatinine and slightly higher body mass index, diabetes prevalence and worse baseline functional status scores. Baseline systolic blood pressure was also slightly higher in women. However, there was no difference by gender or by treatment in baseline characteristics for age, diastolic blood pressure or background medications.
Clinical Outcomes by Baseline Left Ventricular Ejection Fraction in the African American Heart Failure Trial (Presentation #837-7)
Data suggest that BiDil, when combined with standard heart failure treatment, is effective in black patients with heart failure regardless of the severity of left ventricular remodeling. In this analysis from A-HeFT, self-identified black heart failure patients received echocardiograms at baseline and again at six months to measure specific cardiac parameters, including left ventricular ejection fraction (LVEF). LVEF describes the ratio of the volume of blood pumped to the body with each heart beat as compared to the amount of blood the left ventricle can hold. While a healthy person has a LVEF of 55 percent or more, many heart failure patients experience a considerably lower LVEF. In these patients, as the heart's ability to pump blood declines, the left ventricle enlarges (remodeling) to accommodate more blood volume. In this study, the mean LVEF was 35 + or - 9 percent. Data suggest the following:
- Heart failure patients with baseline LVEF < or = 35 percent are at higher risk of mortality and morbidity compared to patients with baseline LVEF >35 percent
- The benefit of BiDil on mortality and morbidity in black patients with symptomatic heart failure was maintained in patients with baseline LVEF < or = 35 percent or >35 percent
- BiDil provided a greater absolute survival benefit in patients with baseline LVEF < or = 35 percent, due to these patients' higher risk for death
- BiDil provided a greater absolute event-free survival benefit in patients with baseline LVEF >35, due these patients' lower risk for death and time to first hospitalization for heart failure
- BiDil benefited A-HeFT patients with LV remodeling, regardless of severity
It has been well established that LV structural remodeling is associated with heart failure progression. Current standard therapies that exert an anti-remodeling effect on the left ventricle, such as ACE inhibitors and beta-blockers, have been shown to have a favorable impact on both heart failure symptoms as well as on long-term heart failure morbidity and mortality. The incremental benefit of BiDil on heart failure morbidity and mortality was observed in patients who were generally already treated with ACE inhibitors and beta-blockers.
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®/Revatio(TM), Levitra®, Cialis®) 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 through a nationwide, dedicated contract sales force.
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, 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: the potential impact of data derived from these studies, if any; unanticipated difficulties in obtaining regulatory approval with regard to new clinical data, if pursued; patient, physician and third-payer acceptance of BiDil as a safe and effective therapeutic; the Company's ability to obtain the substantial additional funding required to conduct manufacturing, marketing and sales of BiDil and to complete its current research activities; unanticipated difficulties in maintaining regulatory approvals to market and sell BiDil; adverse side effects experienced by patients; the Company's ability to obtain or maintain intellectual property protection and required licenses and other factors discussed in its Annual Report on Form 10-K for the year ended December 31, 2005, which has been filed with the SEC. In addition, 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.
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