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NitroMed Presents BiDil(R) Data on Reverse Remodeling in Heart Failure Patients at HFSA Meeting

Posted on: Wednesday, 21 September 2005, 09:00 CDT

NitroMed, Inc. (NASDAQ: NTMD) announced new data today during the late-breaking session of the annual meeting of the Heart Failure Society of America (HFSA), being held September 18-21. The data, presented by Dr. Jay Cohn, professor of medicine at the University of Minnesota and member of the Steering Committee for the African American Heart Failure Trial (A-HeFT) which was co-sponsored by NitroMed and the Association of Black Cardiologists, suggest that BiDil(R) (isosorbide dinitrate/hydralazine hydrochloride) can inhibit left ventricular (LV) remodeling in patients with severe heart failure.

It has been well established that LV structural remodeling is associated with heart failure progression. Current standard therapies such as ACE inhibitors and beta-blockers that exert an anti-remodeling effect on the left ventricle have been shown to have a favorable impact on both heart failure symptoms as well as on long-term heart failure morbidity and mortality.

In the analysis presented at HFSA, self-identified black heart failure patients randomized from the A-HeFT trial received echocardiograms at baseline and again at six months. Echocardiograms from 678 patients performed both at baseline and at six months were analyzed for specific cardiac parameters including left ventricular ejection fraction (LVEF) and left ventricular internal diastolic dimension at diastole (LVIDD). Blood samples were also obtained at baseline and at six months from 683 patients for determination of plasma BNP levels. Researchers found no significant differences between groups at baseline, but at six months, patients taking BiDil plus standard therapy had significant decreases in LVIDD and significant increases in LVEF as compared to patients taking placebo plus standard therapy. These LVIDD and LVEF changes resulted in reversal of the LV remodeling process. Moreover, plasma BNP levels, a diagnostic marker for heart failure, were substantially reduced in the BiDil plus standard therapy treatment group, as compared to the placebo plus standard therapy group.

Specifically, after six months of treatment;

-- LVEF increased by 2.82 percentage units in the BiDil group vs. 0.77 percentage units in the control group (P=0.0025)

-- LVIDD decreased by 0.22 cm in the BiDil group vs. 0.00 cm in the control group (P=0.0062)

-- Plasma BNP concentration was decreased by 27.7% in the BiDil group vs. 13.4% in the control group (P=0.051)

"The observed changes in LVIDD and LVEF in these severe heart failure patients were statistically significant and are consistent with the clinical outcomes from A-HeFT," commented Dr. Cohn. "These results point to an anti-remodeling effect of the drug, over and above the already known benefits of ACE inhibitors and beta-blockers."

BiDil was recently approved by the U.S. Food and Drug Administration (FDA) and launched by NitroMed, Inc. in July 2005. It is indicated to improve survival, prolong time to hospitalization for heart failure and improve patient-reported functional status, as an adjunct to current standard heart failure therapy in self-identified black patients. The FDA based the approval of BiDil primarily on results from the A-HeFT trial, which was halted early, in July 2004, due to the significant survival benefit seen with the drug. NitroMed plans to submit the data presented today to FDA before year-end, as a supplement to the data that formed the basis of BiDil's regulatory approval.

Heart failure is a progressively worsening condition characterized by the cyclical weakening of the heart muscle and impairment of the ventricles' ability to fill with or eject blood. Symptoms predominantly occur due to an impairment of left ventricular (LV) function, leading to cardiac remodeling. This remodeling is manifested clinically by changes in size, shape, and function of the heart.

BNP is a substance secreted from the ventricles of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure - even someone whose condition is stable - is higher than in a person with normal heart function(1).

BiDil Data at HFSA

In addition to today's presentation, titled "Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine Inhibits Left Ventricular Remodeling in Well-Treated Severe Heart Failure in African Americans: A-HeFT", five additional BiDil abstracts as titled below were presented over the course of the HFSA meeting, held September 18 - 21:

-- In-Trial Economic Evaluation of a Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure: Results from the African-American Heart Failure Trial (A-HeFT)

-- The Genetic Risk Assessment Sub-Study of the African-American Heart Failure Trial (A-HeFT): Impact of Genetic Variation of NOS3

-- Early, Sustained Event-Free Survival from Fixed-Dose Isosorbide Dinitrate/Hydralazine: Increased Survival Is Consistent across Subgroups in Advanced Heart Failure

-- Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine Reduces Heart Failure Hospitalizations, Length of Stay, and Cost in African-American Heart Failure Trial (A-HeFT)

-- Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine Improves Quality of Life in African Americans with Heart Failure: Results from A-HeFT

Michael D. Loberg, Ph.D., President and CEO of NitroMed commented, "As exemplified by our six presentations at HFSA, there is strong interest in BiDil within the medical and scientific community, as we continue to gain important knowledge from the A-HeFT database. We are continuing to analyze this database to best determine how BiDil works in the patient population most likely to benefit from this important new medicine."

About BiDil

BiDil 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.

BiDil is a fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride. While the exact mechanism of action underlying the beneficial effects of BiDil in the treatment of heart failure is unknown, it is known that isosorbide dinitrate is a vasodilator with effects on both arteries and veins. The dilator properties of nitrates result from the release of nitric oxide that leads to the relaxation of vascular smooth muscle. Hydralazine is an arterial vasodilator.

In A-HeFT, self-identified black patients taking BiDil in addition to current standard heart failure therapies experienced a significant 43 percent decrease in the risk of mortality (P=.012) (absolute mortality rate: BiDil, 6.2% vs. placebo, 10.2%), a 39 percent reduction in the risk of first hospitalization for heart failure (P less than .001) (absolute first hospitalization rate: BiDil, 16.4% vs. placebo, 24.4%) 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 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. 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%) and dizziness (32%) 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(R) (isosorbide dinitrate/hydralazine hydrochloride), an orally administered medicine that may be prescribed 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 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 is marketed by NitroMed through a nationwide, dedicated 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, including statements regarding the Company's expectations about the new clinical data regarding BiDil, the benefits of BiDil and its plans to make BiDil available to patients who can gain from its therapeutic benefits, 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: unanticipated difficulties in obtaining regulatory approval with regard to new clinical data, maintaining existing regulatory approvals to market and sell BiDil; the Company's ability to develop and maintain the necessary sales, marketing and manufacturing capabilities to launch and commercialize BiDil; patient, physician and third-payer acceptance of BiDil as a safe and effective therapeutic; adverse side effects experienced by patients taking BiDil; the Company's ability to obtain or maintain intellectual property protection and required licenses; the Company's ability to obtain the substantial additional funding required to conduct manufacturing, marketing and sales of BiDil and other factors discussed in its Quarterly Report on Form 10-Q for the Quarter ended June 30, 2005, which is 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.

For full prescribing information, visit: www.BiDil.com.

BiDil is a registered trademark of NitroMed, Inc.

(1)Cleveland Clinic Foundation

Source: Business Wire

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