Single Molecule with Dual Mechanism May Offer Novel Approach to Blood Pressure Management NEW ORLEANS, May 16
NEW ORLEANS, May 16 /PRNewswire-FirstCall/ -- Pharmacopeia (Nasdaq: PCOP),
an innovator in the discovery and development of novel small molecule
therapeutics, announced today that PS433540, its first-in-class Dual Acting
Receptor Antagonist (DARA), showed statistically significant blood pressure
reductions in a Phase 2a study in patients with mild to moderate hypertension.
PS433540 is being developed as a potential treatment for both hypertension and
diabetic nephropathy and is a novel blood pressure product candidate that
possesses two validated mechanisms of action in a single molecule. The data
will be presented today at the Recent and Late Breaking Clinical Trials
Session at the American Society of Hypertension (ASH) Twenty-Third Annual
Scientific Meeting and Exposition in New Orleans.
The Phase 2a study met its primary endpoint by showing a statistically
significant reduction in mean 24-hour systolic ambulatory blood pressure over
placebo. The study also showed statistically significant improvements over
placebo in mean 24-hour diastolic ambulatory blood pressure as well as seated
blood pressure. In this double-blind, placebo-controlled study, patients
treated with 200 mg of PS433540 once daily experienced a 12/9mmHg drop in mean
24-hour systolic and diastolic blood pressure and those treated with 500 mg
experienced a 15/10mmHg drop in mean 24-hour systolic and diastolic blood
pressure. These reductions were highly statistically significant vs. placebo
(P<0.001). Mean seated office systolic and diastolic blood pressure, the
typical blood pressure measure, was also evaluated, with observed blood
pressure drops of 17/11mmHg with the 200 mg dose and 17/10mmHg with the 500 mg
dose (P<0.001 vs. placebo).
Once-daily treatment with 200 or 500 mg of PS433540 was well tolerated.
Most of the adverse events reported were mild or moderate in severity and
included headaches and minor musculoskeletal and respiratory complaints. All
of these events occurred with similar frequency in the three treatment groups.
There was one case of peripheral edema in the placebo arm and one case of
peripheral edema in one of the treated arms. There were no increases in liver
enzymes above 2 times the upper limit of normal. On average, liver enzyme
levels tended to decrease from baseline in the treated arms. There were no
serious adverse events on PS433540 treatment. Three subjects discontinued
therapy for adverse events, all of which were in the placebo group.
The leading, single-therapy antihypertensives across a broad range of
classes, according to their labels, have the ability to lower seated office
blood pressure up to 12/8mmHg.(1) Data show that a 2mmHg reduction in blood
pressure decreases the average death rate from coronary heart disease by an
estimated 4 percent and stroke by 6 percent.(2)
"These positive results indicate that PS433540 may be a unique new
treatment option for physicians and patients," said Joel Neutel, M.D.,
Associate Professor of Medicine in the Department of Medicine at the
University of California in Irvine, and Medical Director of Clinical
Pharmacology at the Orange County Research Center in Tustin, CA, who was the
lead investigator of the Phase 2a study. "The magnitude of the blood pressure
reductions we saw in this study were very impressive, and we look forward to
further evaluating the benefits of this novel compound."
An estimated 73 million Americans suffer from high blood pressure, a major
risk factor for cardiovascular events and heart disease.(3) More than half of
people diagnosed and treated with high blood pressure never reach suggested
treatment goals and those who do often require two or more medications.(4)
PS433540 is the first and only compound specifically designed to incorporate
two proven mechanisms -- endothelin (ETA) and angiotensin (AT1) receptor
blockade -- in one molecule to treat high blood pressure.
"We are very pleased with the results of this important Phase 2a trial and
look forward to future studies which will further assess the potential of
PS433540, perhaps even beyond blood pressure lowering," said Joseph A.
Mollica, Ph.D., Chairman of the Board and Interim President and Chief
Executive Officer of Pharmacopeia. "We believe PS433540's dual mechanism of
action may have a positive effect on diabetic kidney disease."
Patients with diabetes are at an increased risk for many complications,
including high blood pressure and diabetic kidney disease. Up to 73 percent of
patients with diabetes have been or are being treated for high blood
pressure,(5) and an estimated 20-30 percent of diabetic patients will progress
to diabetic kidney disease,(6) a devastating disease that may require patients
to undergo dialysis or a kidney transplant.(7)
Pharmacopeia recently initiated a 12-week, Phase 2b clinical trial with
PS433540 to evaluate the compound's safety and efficacy at three different
doses versus placebo in 375 subjects with Stage I and Stage II hypertension.
The study will also compare blood pressure reductions for each dose with
irbesartan. Pharmacopeia anticipates completion of the Phase 2b trial at the
end of 2008.
About the Phase 2a study
In this prospective study, 234 men and women with Stage I and Stage II
hypertension entered into a single blind placebo run-in period for 3-4 weeks,
after which 114 were randomized to receive double blind study medication for
four weeks. At the time of the database lock, 108 subjects were available for
evaluation, 93 of whom had both baseline and follow-up ambulatory blood
pressure measurements (placebo: 25; PS433540 200mg: 35; PS433540 500mg: 33).
The primary endpoint was the subjects' change from baseline in mean 24-hour
systolic ambulatory blood pressure after 4 weeks of treatment. Additionally,
investigators evaluated 24-hour diastolic ambulatory blood pressure and mean
seated office systolic and diastolic blood pressure as well as a number of
other endpoints.
Investor event at ASH
Pharmacopeia will host a meeting for investors today, Friday, May 16th at
7:00am CDT (8:00am EDT) to review the Phase 2a study results from its PS433540
program, including a presentation by Joel Neutel, M.D., the study's lead
investigator. A live webcast and 90-day archive of the presentation can be
accessed on the Investors section of the company's website at
http://www.pharmacopeia.com.
About PS433540
PS433540 is the first and only blood pressure product candidate in a new
class of antihypertensives known as Dual Acting Receptor Antagonists (DARAs).
PS433540 is being developed as a potential treatment for hypertension and
diabetic nephropathy. PS433540 possesses two clinically validated mechanisms
of action in a single molecule. There is preclinical and initial clinical data
suggesting that compared to either mechanism alone, simultaneously blocking
angiotensin II and endothelin 1 at their respective receptors, AT1 and ETA,
may provide an improved treatment option for several cardiovascular diseases.
Because PS433540 is highly selective for the AT1 and ETA receptors it is able
to block the blood pressure-raising actions of angiotensin and endothelin when
they bind to these receptors.
About Pharmacopeia
Pharmacopeia is a clinical development stage biopharmaceutical company
dedicated to discovering and developing novel small molecule therapeutics to
address significant medical needs. The company has a broad portfolio of
clinical and preclinical candidates under development internally or by
partners including eight clinical compounds in Phase 2 or Phase 1 development
addressing multiple indications including hypertension, diabetic nephropathy,
muscle wasting, inflammation and respiratory disease. The company is
leveraging its fully integrated drug discovery platform to sustain the growth
of its development pipeline. Pharmacopeia has established strategic alliances
with major pharmaceutical and biotechnology companies, including Bristol-Myers
Squibb, Celgene, Cephalon, GlaxoSmithKline, Schering-Plough, and Wyeth
Pharmaceuticals. For more information please visit the company's website at
http://www.pharmacopeia.com.
Investor Contacts:
Amy P. Sharpless
Pharmacopeia, Inc.
609-452-3643
ir_pr@pcop.com
Carney Noensie
Burns McClellan
212-365-0983
cnoensie@burnsmc.com
Media Contact:
Glenn Silver
Chamberlain Healthcare Public
Relations
212-389-9158
gsilver@chamberlainpr.com
This press release, and oral statements made with respect to information
contained in this press release, constitute forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include those which express plan, anticipation,
intent, goal, contingency or future development and/or otherwise are not
statements of historical fact. These statements are based upon management's
current expectations and are subject to risks and uncertainties, known and
unknown, which could cause actual results and developments to differ
materially from those expressed or implied in such statements. These forward-
looking statements include, but are not limited to, statements about the
results of Pharmacopeia's Phase 2a clinical study of PS433540, a product
candidate from its DARA program, Pharmacopeia's plans to develop PS433540,
Pharmacopeia's other Phase 2 and Phase 1 clinical studies with respect to
PS433540, including timing and expected outcomes of such studies,
Pharmacopeia's estimates of the market opportunities for PS433540, the
implementation of Pharmacopeia's strategic plans, Pharmacopeia's plans to
develop PS178990, a product candidate from its SARM program, Pharmacopeia's
Phase 1 clinical studies with respect to PS178990, including timing and
expected outcomes of such studies, Pharmacopeia's plans to develop PS031291, a
product candidate from its chemokine receptor CCR1 program, Pharmacopeia's
estimates of the market opportunities for its other product candidates,
including PS178990 and PS031291, Pharmacopeia's ability to raise additional
capital, Pharmacopeia's anticipated operating results, financial condition,
liquidity and capital resources, Pharmacopeia's ability to successfully
perform under its collaborations with Bristol-Myers Squibb, Cephalon,
GlaxoSmithKline, Schering-Plough and Wyeth, Pharmacopeia's ability to build
its pipeline of novel drug candidates through its own internally-funded drug
discovery programs, third party collaborations and in-licensing,
Pharmacopeia's expectations concerning the development priorities of its
collaborators, their ability to successfully develop compounds and its receipt
of milestones and royalties from the collaborations, Pharmacopeia's
expectations concerning the legal protections afforded by U.S. and
international patent law, Pharmacopeia's ability to pursue the development of
new compounds and other business matters without infringing the patent rights
of others, additional competition, and changes in economic conditions.
Further information about these and other relevant risks and uncertainties
may be found in Pharmacopeia's Reports on Form 8-K, 10-Q and 10-K filed with
the U.S. Securities and Exchange Commission. Pharmacopeia urges you to
carefully review and consider the disclosures found in its filings which are
available in the SEC EDGAR database at http://www.sec.gov and from
Pharmacopeia at http://www.pharmacopeia.com. All forward-looking statements in
this press release and oral statements made with respect to information
contained in this press release are qualified entirely by the cautionary
statements included in this press release and such filings. These risks and
uncertainties could cause actual results to differ materially from results
expressed or implied by such forward-looking statements. These forward-looking
statements speak only as of the date of this press release. Pharmacopeia
undertakes no obligation to (and expressly disclaims any such obligation to)
publicly update or revise the statements made herein or the risk factors that
may relate thereto whether as a result of new information, future events, or
otherwise.
(1) Prescribing Information for Coreg CR(R), Lotensin(R), Avapro(R),
Benicar(R) and Norvasc(R)
(2) American Heart Association news release.
http://americanheart.mediaroom.com/index.php?s=43&item=59. Accessed
April 7, 2008.
(3) AHA 2007 Heart Disease and Stroke Statistics, p. 3.
(4) Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the
Joint National Committee on Prevention, Detection, valuation, and
Treatment of High Blood Pressure. Journal of the American Medical
Association. 2003;289:p.2560-2572.
(5) American Diabetes Association:
http://www.diabetes.org/utils/printthispage.jsp?PageID=STATISTICS_233192.
Accessed April 4, 2008.
(6) Diabetes Care, Volume 27, Supplement 1, January 2004.
(7) National Institute of Diabetes and Digestive and Kidney Diseases.
http://kidney.niddk.nih.gov/kudiseases/pubs/pdf/kdd.pdf. Accessed
April 24, 2008.
SOURCE Pharmacopeia
