SIRIUS II Trial Suggests Ularitide Holds Promise as New Treatment for Acute
Decompensated Heart Failure
FREMONT, Calif., Sept. 4 /PRNewswire-FirstCall/ -- Protein Design Labs,
Inc. (PDL) (Nasdaq: PDLI) today announced positive data from a phase 2
clinical study of ularitide -- the synthetic version of a natriuretic peptide
produced in the kidney known as urodilatin -- as a potential treatment for
patients with acute decompensated heart failure (ADHF). The data from the
SIRIUS II trial were presented at the annual European Society of Cardiology
(ESC) Congress, the largest cardiology meeting in Europe, which is taking
place September 3-7 in Stockholm, Sweden.
"The results of the SIRIUS II study show ularitide to be well-tolerated
and indicate clear, dose-dependent favorable effects in treating the symptoms
of ADHF without compromising kidney function," said Veselin Mitrovic, M.D.,
Medical Director of the Research Unit / Kerckhoff Clinic, Bad Nauheim. "Based
on the overall findings, ularitide holds potential as a treatment for ADHF
patients."
"We are very pleased with the results of the SIRIUS II trial and are
optimistic about ularitide's potential as a treatment for ADHF patients based
on data to date," said Steve Benner, M.D., Senior Vice President and Chief
Medical Officer, PDL. "We are committed to moving ularitide ahead, and
therefore look forward to initiating new clinical studies in the United States
and Europe to facilitate its global development."
The SIRIUS II trial was a randomized, double-blind, placebo-controlled
clinical trial conducted at 19 centers across Europe. A total of 221
patients were randomized equally to receive ularitide 7.5, 15, or 30 ng/kg/min
given intravenously as a 24-hour infusion, or placebo. The two primary
endpoints in the study were change in dyspnea (shortness of breath) score and
change in pulmonary capillary wedge pressure (PCWP), a measurement of lung
vessel pressure, at six hours. Secondary endpoints included serum creatinine
levels (a standard measure of kidney function), length of hospital stay and
mortality.
Ularitide treatment was associated with a significantly improved dyspnea
score (p<0.05) in all three dosing groups compared to placebo. Dyspnea was
assessed using a standard dyspnea scale, which measures a patient's perception
of their change in shortness of breath from the start of drug therapy. More
patients reported moderate to marked improvement in dyspnea in all of the
three treatment groups compared to placebo.
The findings also demonstrated a significant decrease in pulmonary
pressure (p<0.05) as measured by PCWP at six hours. These changes were also
associated with an increase in cardiac index (a measure of heart function) in
the 15 and 30 ng/kg/min groups. At six hours, PCWP dropped 10-12 mmHg on
average from baseline for those treated with ularitide, compared to those on
placebo, for whom PCWP dropped 4 mmHg from baseline.
Additional SIRIUS II Results
Secondary endpoints of the SIRIUS II study evaluated serum creatinine
levels, length of hospital stay and mortality.
Serum creatinine levels were unchanged in patients treated with ularitide
compared to placebo through 72 hours. This finding suggests that ularitide
did not negatively affect kidney function in study patients. Length of
hospital stay, measured in median hours in hospital, was lower for the 15 and
30 ng/kg/min groups, compared to the placebo and 7.5 ng/kg/min groups. The
length of hospital stay was lowest for the 15 ng/kg/min (122 hours) and
30 ng/kg/min (158 hours) groups, compared to the placebo (200.5 hours) and
7.5 ng/kg/min (192 hours) groups.
There was no increase in mortality in the ularitide treatment groups
compared to placebo. The mortality rate through day 30 was higher in the
placebo group compared to the three ularitide groups: 13.2% in the placebo
group and 3.3% (p=0.080, compared to placebo), 3.8% (p=0.16), and 1.8%
(p=0.029) in the 7.5, 15 and 30 ng/kg/min groups, respectively.
Ularitide was well tolerated by patients in the study. The most frequent
adverse event was hypotension, which occurred in 1.9% of placebo patients and
in 8.3%, 11.3%, and 16.4% of patients in the 7.5, 15, and 30 ng/kg/min groups,
respectively. Other adverse events that occurred in greater than 2% of the
ularitide-treated patients were blood pressure decrease (5.4% ularitide vs. 0%
placebo), cardiac failure (4.8% ularitide vs. 1.9% placebo), sweating increase
(4.2% ularitide vs. 0% placebo), dizziness (3.6% ularitide vs. 1.9% placebo),
and asthenia (2.4% ularitide vs. 0% placebo). The frequency of serious adverse
events through day 30 was comparable among the groups.
SIRIUS II results will also be presented as a poster at the 9th Annual
Scientific Meeting of the Heart Failure Society of America on September 19 in
Boca Raton, Florida.
The SIRIUS II clinical trial was conducted by CardioPep Pharma GmbH. PDL
holds exclusive development and marketing rights for ularitide for all
indications worldwide. PDL intends to file a U.S. IND later this year and to
proceed with the global development of ularitide as a treatment for ADHF.
About Ularitide
Ularitide is a synthetic form of urodilatin, which is a naturally
occurring human protein that belongs to the family of natriuretic peptides and
is produced in the kidney where it regulates levels of fluid and sodium.
Urodilatin is excreted into the urine and exists in low levels in the systemic
blood circulation. The peptide was first isolated by scientists affiliated
with the group of Wolf-Georg Forssmann at Heidelberg University, and has been
developed by a German company, CardioPep Pharma GmbH.
When injected into the blood stream, ularitide causes relaxation of blood
vessels, specifically in the arteries that feed the kidneys, lungs and heart,
and stimulates natriuresis (excretion of abnormal amounts of sodium into the
urine) and diuresis (increase in urination). These effects suggest a
potential therapeutic role for ularitide in patients with ADHF.
About Acute Decompensated Heart Failure
Congestive heart failure is a serious chronic medical condition in which
the heart is unable to maintain adequate circulation of blood in the tissues
of the body or to pump out the venous blood returned to it by the venous
circulation. In the advanced stages of heart failure, the heart is unable to
meet the body's demand for oxygen and congestion or fluid retention can occur
in the lungs and other areas throughout the body. Patients who experience a
gradual or sudden worsening of CHF may experience severe symptoms resulting in
ADHF. Patients with ADHF require emergency treatment and can require
hospitalization.
ADHF can result from an acute event (e.g. heart attack, acute myocardial
infarction). During an acute episode, the inability of the heart to adequately
circulate blood throughout the body worsens, kidney function may be diminished
and the patient may experience difficulty in breathing.
According to current statistics from the American Heart Association, there
are about five million heart failure patients in the United States, and
550,000 new cases of heart failure diagnosed in the United States every year.
This includes 10 out of every 1,000 people over the age of 65. Of newly
diagnosed patients under the age of 65, about 80 percent of the men and 70
percent of the women will die within eight years. In people diagnosed with
heart failure, sudden cardiac death occurs at six to nine times the rate of
the general population. In the United States alone, there are approximately
one million hospitalizations per year for ADHF.
About Protein Design Labs
PDL is a biopharmaceutical company focused on the research, development
and commercialization of novel therapies for inflammation and autoimmune
diseases, acute cardiac conditions and cancer. PDL markets several products
in the United States through its hospital sales force and wholly-owned
subsidiary, ESP Pharma, Inc. As a leader in the development of humanized
antibodies, PDL has licensed its patents to numerous pharmaceutical and
biotechnology companies, some of which are now paying royalties on net sales
of licensed products. Further information on PDL is available at http://www.pdl.com.
The foregoing contains forward-looking statements involving risks and
uncertainties and PDL's actual results may differ materially from those in the
forward-looking statements. Factors that may cause such differences are
discussed in the Company's Annual Report on Form 10-K for the year ended
December 31, 2004, in its Quarterly Report on Form 10-Q for the quarter ended
June 30, 2005 and in other filings made with the Securities and Exchange
Commission. In particular, results obtained in the phase 2 study may not be
predictive of results to be obtained in the additional evaluations that would
be necessary to demonstrate ularitide to be safe and effective in the
treatment of decompensated congestive heart failure, nor can there be
assurance that PDL will initiate subsequent clinical trials of ularitide. All
statements included in this press release are based upon information available
to PDL as of the date hereof, and PDL assumes no obligation to update any such
forward-looking statements.
NOTE: Protein Design Labs and the PDL logo are registered U.S. trademarks
of Protein Design Labs, Inc.
SOURCE Protein Design Labs
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Related links:
http://www.pdl.com
CONTACT:
Investors, James R. Goff, +1-510-574-1421, or
jgoff@pdl.com, or Jean Suzuki (at ESC), Product Communications,
+1-510-574-1550, or jsuzuki@pdl.com, both of Protein Design Labs;
or Jade Cantor (at ESC) of Lazar Partners, +1-917-650-7757, or
jcantor@lazarpartners.com, for Protein Design Labs
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