Titan Pharmaceuticals,
Inc.
|
Company: Executive Vice President & CFO 650-244-4990 |
Media/Investors: Jonathan Fassberg The Trout Group 212-477-9077 |
TITAN
INITIATES RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED PHASE II CLINICAL STUDY
OF DITPA IN CONGESTIVE HEART FAILURE
South San
Francisco, CA – December 14, 2004 – Titan Pharmaceuticals Inc., announced
today that the company has initiated a randomized, double blind, Phase IIb
study of DITPA, its novel product in development for treatment of
cardiovascular disease. This study will
evaluate DITPA in the treatment of advanced congestive heart failure (CHF)
associated with low serum thyroid hormone levels. DITPA, or
3,5-diiodothyropropionic acid, is a novel analogue of thyroid hormone selected
for its potential to improve congestive heart failure while avoiding
limitations inherent in the use of current thyroid hormone medications in
patients with cardiovascular disease.
Thyroid hormone is an
important regulator of the heart and blood vessels, and adequate levels of
thyroid hormone are essential for proper function of the cardiovascular system.
Thyroid hormone improves the ability of the heart to fill properly (improves
diastolic function), reduces the pressure against which the heart pumps by
relaxing small blood vessels (reduces peripheral vascular resistance), and
improves the efficiency of contraction of the heart so that a greater amount of
blood is pumped per contraction (improved systolic function).
Researchers have demonstrated
that approximately 30% of patients with advanced (NYHA Class III and IV)
congestive heart failure have abnormally low levels of T3, the active
form of thyroid hormone needed by heart cells, and that low levels of T3 are a strong
independent predictor of increased mortality in CHF patients. It is estimated
that approximately 1 million CHF patients collectively in the
The important role of thyroid
hormone in maintaining heart and blood vessel function, and the association of
low T3
and increased mortality in CHF suggest a potential role for DITPA as a thyroid
hormone replacement therapy in CHF.
Currently available thyroid hormone medications are generally not
suitable for chronic use in CHF, because they are primarily T4 preparations,
or have too short a half-life, and have the potential to increase heart rate,
which is an unwanted side effect in CHF patients.
DITPA is a novel analogue of
thyroid hormone (T3), that has demonstrated in preclinical and
preliminary, placebo controlled pilot clinical testing the ability to improve
measures of diastolic function, reduce peripheral vascular resistance, and
improve systolic function, without increasing heart rate. Such pilot clinical
testing in CHF patients over 4 weeks also demonstrated no significant adverse
effects.
Titan’s current Phase IIb
randomized, placebo controlled study will evaluate 150 patients with NYHA Class
III-IV CHF and low serum T3 levels. Patients will receive either of two doses of
DITPA or placebo for six months. The study will be performed at 35 centers in
the
“We are pleased to initiate
this clinical study of DITPA, an important milestone in the DITPA development
program,” stated Dr. Louis R. Bucalo, Chairman, President and CEO of Titan.
In addition to evaluating
DITPA in CHF patients with low T3 levels, the Company believes that DITPA may also have
potential utility in the treatment of diastolic dysfunction, and the treatment
of patients with left ventricular dysfunction after myocardial infarction.
Diastolic dysfunction, or
failure of the heart to fill adequately, is the primary cause of cardiac
dysfunction in approximately 25 percent of the estimated 8 million people in
the
Left ventricular dysfunction
after myocardial infarction is characterized by subsequent extension of the
area of infarction, hypertrophy of the surviving heart muscle without increase
in its blood supply leading to inadequate heart muscle perfusion, and gradual
replacement of heart muscle cells with fibrosis, a process called pathological
ventricular remodeling. Worsening of CHF due to subsequent infarct expansion,
and pathologic ventricular hypertrophy and remodeling is a major cause of
morbidity and mortality in patients with CHF.
Thyroid hormone is known to
promote growth of small blood vessels in the heart, and has also been
demonstrated in animal models to convert pathologic hypertrophy to more adequately
perfused heart muscle. Recent preclinical studies demonstrate that DITPA also
stimulates coronary small blood vessel growth after myocardial infarction, and
reduced extension of infarct size by approximately 80 percent. In these
studies, DITPA was also shown to reduce ventricular remodeling subsequent to
myocardial infarction, and improve heart function.
Additional support for
evaluation of DITPA in this setting is the finding that thyroid hormone levels
decrease in patients after myocardial infarction, and the extent of the
decrease correlates with long term outcome. Specifically, patients whose
thyroid hormone levels remain below normal in the weeks following myocardial
infarction have a significantly increased mortality two years after myocardial
infarction.
Based on these and other
research studies, the Company may pursue approaches to evaluation of DITPA in
these additional clinical settings.
DITPA is also currently being
evaluated in a second randomized, double blind, placebo controlled Phase II
study in 150 patients with NYHA Class II-IV CHF, sponsored by the Department of
Veterans Affairs Cooperative Studies Program and funded by a $3.8 million
grant.
About Titan Pharmaceuticals
Titan Pharmaceuticals, Inc. (ASE:
TTP) is a biopharmaceutical company focused on the development and
commercialization of novel treatments for central nervous system disorders,
cancer and cardiovascular disease. Titan's products in development utilize
novel technologies that have the potential to significantly improve the
treatment of these diseases. Titan also establishes partnerships with
government institutions and other leading pharmaceutical development
companies. For more information, please
visit the Company’s website at www.titanpharm.com
The press release may
contain "forward-looking statements" within the meaning of Section
27A of the Securities Act of 1933 and Section 21E of the Securities Exchange
Act of 1934. Such statements include, but are not limited to, any statements
relating to the Company's development program and any other statements that are
not historical facts. Such statements involve risks and uncertainties,
including, but not limited to, those risks and uncertainties relating to
difficulties or delays in development, testing, regulatory approval, production
and marketing of the Company's drug candidates, unexpected adverse side effects
or inadequate therapeutic efficacy of the Company's drug candidates that could
slow or prevent product development or commercialization, the uncertainty of patent
protection for the Company's intellectual property or trade secrets and the
Company's ability to obtain additional financing if necessary. Such statements
are based on management's current expectations, but actual results may differ
materially due to various factors, including those risks and uncertainties
mentioned or referred to in this press release.