Improvement in Survival and Patient-Reported Functional Status,
and Prolonged Time to Hospitalization for Heart Failure Seen With BiDil
LEXINGTON, Mass., June 23 /PRNewswire-FirstCall/ -- NitroMed, Inc.
(Nasdaq: NTMD) announced today that the U.S. Food and Drug Administration
(FDA) approved BiDil(R) (isosorbide dinitrate/hydralazine hydrochloride) for
the treatment of heart failure in black patients.
BiDil 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. 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 the African American Heart
Failure Trial (A-HeFT), received, in addition to BiDil or placebo, a loop
diuretic, an angiotensin converting enzyme inhibitor or an angiotensin
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 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<.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
"In BiDil, we now have a new treatment that has been shown to save the
lives of black heart failure patients, helping a population that is
disproportionately burdened by cardiovascular disease," said Anne Taylor,
M.D., associate dean for faculty affairs, professor of medicine, University of
Minnesota Medical School and lead A-HeFT investigator. "African Americans
between the ages of 45 and 64 are 2.5 times more likely to die prematurely
from heart failure than their non-black counterparts, and they also present
with and die from the disease at an earlier age. FDA approval of BiDil
represents an important leap forward in addressing this health disparity,"
said Dr. Taylor.
The FDA based the approval of BiDil primarily on results from the recent
A-HeFT trial, which was halted early, in July 2004, due to the significant
survival benefit seen with the drug. Co-sponsored by NitroMed and the
Association of Black Cardiologists (ABC), A-HeFT was the first clinical trial
conducted in a heart failure population in which all of the participants
identified themselves as black. A retrospective analysis of an earlier study
with a combination of isosorbide dinitrate and hydralazine hydrochloride had
suggested a trend for improved survival in the subset of patients with mild to
moderate heart failure who self-identified as black.
"BiDil has the ability to significantly extend and enhance the lives of
black patients with heart failure," said Michael D. Loberg, Ph.D., president
and chief executive officer, NitroMed, Inc. "NitroMed looks forward to
bringing this important medicine to the patients and physicians who need it."
BiDil is a fixed-dose combination of isosorbide dinitrate and hydralazine
hydrochloride. While the exact mechanism of action of BiDil 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 dilator.
BiDil treatment is orally-administered and is initiated at a dose of one
tablet, three times per day, and may be increased to a maximum of two tablets,
three times per day, based on patient tolerance. Adjustments to maximum
dosage may occur in three to five days; however, adverse side effects, which
may include headaches and dizziness, may require that some patients take more
time to reach their highest tolerated dose.
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.
There is no cure for this disease, and more than 50 percent of patients die
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.
Clinical data supporting the safety and efficacy of BiDil were derived
primarily from the African American Heart Failure Trial (A-HeFT), which was
conducted from 2001 to 2004. Also considered were two trials conducted in the
1980s, the Vasodilator Heart Failure Trial I and Vasodilator Heart Failure
Trial II (V-HeFT I and II).
A-HeFT was a randomized, double-blind, placebo-controlled study enrolling
1,050 self-identified black patients with New York Heart Association class III
and IV heart failure at 169 clinical research sites. Study results were
published in the New England Journal of Medicine in November 2004.
Augmentation of the vasodilatory effects of isosorbide dinitrate by
phosphodiesterase inhibitor drugs (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. Symptomatic hypotension may occur with even
small doses of BiDil. Should be used with caution in volume depleted or
hypotensive patients. Hydralazine can cause tachycardia potentially leading
to myocardial ischemia and anginal attacks. Caution should be exercised if
BiDil is used with MAO inhibitors and alcohol.
Adverse events reported in the trial and seen more frequently in the group
given BiDil included symptoms of headache (50 percent in BiDil patients vs. 21
percent in placebo patients) and dizziness (32 percent in BiDil patients vs.14
percent in placebo patients).
About NitroMed, Inc.
NitroMed is an emerging pharmaceutical company focused on the research,
development and commercialization of proprietary pharmaceuticals based on the
therapeutic benefits of the naturally occurring molecule nitric oxide. The
Company uses its expertise in nitric oxide biology and chemistry in an effort
to develop both new pharmaceuticals, as well as safer, more effective versions
of existing drugs. Research and development efforts focus on major diseases
that are characterized by a deficiency in nitric oxide, such as cardiovascular
and inflammatory diseases. Corporate collaborations are also an element of the
Company's business strategy, and NitroMed has an agreement with Boston
Scientific to jointly develop nitric oxide-enhanced cardiovascular stents.
Forward Looking Statements
Any statements in this press release about future expectations, plans and
prospects for the Company, including the possible therapeutic benefits and
market acceptance of BiDil, 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 maintaining 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 March 31, 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 http://www.BiDil.com.
SOURCE NitroMed, Inc.
CONTACT: Media Contacts: Susannah Budington, +1-301-980-7482, or Amanda
Sellers, +1-202-955-6222, both of Spectrum Science Communications, for
NitroMed, Inc.; or Investor Contact: Lawrence E. Bloch, M.D., J.D., Chief
Financial Officer, Chief Business Officer of NitroMed, Inc., +1-781-266-4197
Web site: http://www.BiDil.com