HACKENSACK, N.J., Sept. 12 /PRNewswire-FirstCall/ -- DOV Pharmaceutical,
Inc. (Nasdaq: DOVP) announced today that bicifadine, its novel non-narcotic
and non-NSAID analgesic, provided statistically and clinically significant
analgesic effects at 400 mg administered three times daily (t.i.d) relative to
a placebo control group. These effects were comparable to the analgesia
produced by the active-control tramadol 100 mg t.i.d. in patients with
moderate-severe pain following bunionectomy surgery. Bicifadine was well-
tolerated with no serious adverse events. This trial is the first of four
pivotal Phase III efficacy trials required for submission of a New Drug
Application to the Food and Drug Administration (FDA) for an indication in the
treatment of acute pain. The current results are consistent with the safety
and efficacy findings from two other double-blind, placebo-controlled studies
in patients with moderate-severe pain following dental surgery.
EFFICACY AND SAFETY RESULTS
The bunionectomy Phase III trial enrolled 325 patients at five sites in
the U.S. The design and analysis of the study compared 200 and 400 mg t.i.d.
of bicifadine to placebo with 100 mg t.i.d. of tramadol as an active control.
The key efficacy endpoint in the study was the analgesic effect seen during
the first eight hours of dosing as measured by the sum of the pain relief and
intensity differences (SPRID-8). Other efficacy measures included the total
of the pain relief scores (TOTPAR-8), the sum of the pain intensity
differences (SPID-8), the time to onset of analgesic effects and the pain
levels measured after the first dosing period. The results showed that both
bicifadine 400 mg t.i.d. and the active control group were statistically
superior (p<0.01) to placebo on the SPRID-8, TOTPAR-8 and SPID-8 analgesia
scores. The onset of analgesic effect was about 30 minutes for both
bicifadine and tramadol. The 200 mg dose of bicifadine resulted in an
analgesic effect intermediate between the 400 mg dose and placebo, but did not
differ statistically from either group. In the repeat dose period, a
conventional endpoint analysis showed that bicifadine 400 mg t.i.d and
tramadol 100 mg t.i.d. were more active than placebo over the course of the
five-day observation period.
Both bicifadine dosing regimens and the tramadol active-control were safe
and well-tolerated. There were no serious adverse events and there were few
dropouts due to adverse events. The percentage of patients with adverse
events judged to be "possibly-definitely" treatment-related in the bicifadine
400 mg t.i.d. group was approximately 20% higher than the placebo group and
did not differ statistically from that of the tramadol control group. The 200
mg t.i.d. dosing arm had the same overall adverse event incidence as the
placebo treatment. Consistent with results from prior studies, the most
common adverse event was related to the gastro-intestinal system, namely,
nausea and emesis for both active treatment groups. Safety measures related
to heart rate, blood pressure, EKGs and clinical laboratory tests showed both
dose regimens of bicifadine to be safe and well-tolerated.
COMPARISON TO PREVIOUS EFFICACY AND SAFETY RESULTS
DOV has previously conducted two placebo-controlled, single-dose, double-
blind, dose-response and active-controlled clinical trials of bicifadine.
These trials were in patients with moderate-severe pain following dental
surgery (third molar extraction) and enrolled approximately 540 and 750
patients. The results of these trials also demonstrated the 400 mg dose of
bicifadine to be superior to placebo and the 200 mg dose to represent the
lower end of the dose-response function for acute post-surgical pain. In all
three studies, bicifadine was well-tolerated.
"Bicifadine is well tolerated and represents a new class of analgesic with
efficacy in moderate to severe acute pain," said Dr. Warren Stern, senior vice
president of drug development at DOV. "Preclinical data suggest that it
should not carry the abuse liability of opioid analgesics. The current results
are notable in that the pain following bunionectomy surgery is generally
regarded to be more severe than that following dental surgery. Additionally,
the dental pain studies evaluated the efficacy and safety of single doses of
bicifadine, whereas the current study evaluated bicifadine effects on repeated
dosing over a five-day period."
THIRD ANNUAL SCIENTIFIC SYMPOSIUM
DOV will hold its Third Annual Scientific Symposium in New York City on
Oct. 28, 2005. "DOV is excited by the prospect of discussing the details of
this bunionectomy trial at our Annual Scientific Symposium," said Dr. Leslie
Hudson, president and CEO. "The Symposium also affords us the opportunity to
review results from the ongoing open label clinical trial in chronic lower
back pain and our strategy for NDA submission of bicifadine for acute and
chronic pain, as well as the status of the other compounds in the DOV
pipeline."
ABOUT BICIFADINE
Bicifadine is a chemically novel molecule with a unique profile of
pharmacological activity. Its primary pharmacological action is to enhance
and prolong the actions of norepinephrine and serotonin by inhibiting the
transport proteins that terminate their physiological actions. While the
Company believes that bicifadine also possesses additional neurochemical
properties that contribute to its analgesic effects, the exact nature of these
other properties is under investigation. Preclinical studies and clinical
trials indicate that either one or a combination of these individual actions
may account for the analgesic properties of bicifadine.
Bicifadine is not a narcotic and, in preclinical studies, it has been
shown not to act at any opiate receptor. In animal models, bicifadine does
not demonstrate abuse, addiction or dependence potential.
Bicifadine has demonstrated statistically significant analgesic effects in
three placebo-controlled clinical trials in patients with pain following third
molar dental and bunionectomy surgery, two models of moderate to severe acute
pain.
ABOUT DOV
DOV is a biopharmaceutical company focused on the discovery, acquisition,
development and commercialization of novel drug candidates for central nervous
system and other disorders, including cardiovascular, that involve alterations
in neuronal processing. Our product candidates address some of the largest
pharmaceutical markets in the world including insomnia, pain, anxiety and
depression. Our partner Neurocrine has filed two NDAs for the use of DOV's
compound indiplon for the treatment of insomnia.
CAUTIONARY NOTE
Statements in this press release that are not historical facts constitute
forward-looking statements within the meaning of Section 27A of the Securities
Act of 1933 and Section 21E of the Securities Exchange Act, each as amended,
including statements regarding our expectations with respect to the progress
of and level of expenses for our clinical trial programs. You can also
identify forward-looking statements by the following words: may, will, should,
expect, intend, plan, anticipate, believe, estimate, predict, potential,
continue or the negative of these terms or other comparable terminology. We
caution you that forward-looking statements are inherently uncertain and are
simply point-in-time estimates based on a combination of facts and factors
currently known by us about which we cannot be certain. Actual results or
events will surely differ and may differ materially from our forward-looking
statements as a result of many factors, some of which we may not be able to
predict or may not be within our control. Such factors may also materially
adversely affect our ability to achieve our objectives and to successfully
develop and commercialize our product candidates, including our ability to:
* demonstrate the safety and efficacy of product candidates at each stage
of development;
* meet our development schedule for our product candidates, including with
respect to clinical trial initiation, enrollment and completion;
* develop an acceptable development plan under and otherwise achieve the
results contemplated by the recent amendment to the existing license
agreement with Merck;
* meet applicable regulatory standards and receive required regulatory
approvals on our anticipated time schedule or at all;
* meet obligations and required milestones under our license and other
agreements;
* obtain and maintain collaborations as required with pharmaceutical
partners;
* obtain substantial additional funds;
* obtain and maintain all necessary patents or licenses; and
* produce drug candidates in commercial quantities at reasonable costs and
compete successfully against other products and companies.
Factors that may cause our actual results to differ materially from our
forward-looking statements include (i) one or more of our product candidates
could be shown to cause harmful side effects, (ii) one or more of our product
candidates may not exhibit the expected therapeutic results, (iii) we or the
FDA may suspend one or more of our clinical trials, (iv) patient recruitment
may be slower than expected or patients may drop out of our clinical trials
including any future trial of ocinaplon if the present clinical hold is
lifted, (v) regulatory approval for our product candidates may not be received
or may be delayed, and (vi) performance of our licensees and collaborative
partners on whom our success depends may not fulfill their obligations to us.
You should also refer to the risks discussed in our other filings with the
Securities and Exchange Commission including those contained in our annual
report on Form 10-K filed on March 15, 2005. We qualify all our forward-
looking statements by these cautionary statements. There may be other factors
that may materially affect our forward-looking statements and our future
results. Readers should not, therefore, place undue reliance on our forward-
looking statements. We do not undertake any obligation and do not intend to
update any forward-looking statement.
SOURCE DOV Pharmaceutical, Inc.
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Related links:
http://www.dovpharm.com
CONTACT:
Barbara Duncan, Chief Financial Officer, or
Alan Beckhard, Manager, Investor Relations and Corporate
Communications, of DOV Pharmaceutical, Inc., +1-201-968-0980
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