Metaphore Pharmaceuticals, Inc. Announces Positive Results of Phase II Clinical Trial
SOD Mimetic M40403 Improved Effectiveness and Predictability of Morphine
FT. LEE, N.J., April 27 /PRNewswire/ -- Metaphore Pharmaceuticals, Inc., a
leading private biotechnology company focused on the development of drugs for
the treatment of pain, autoimmune disorders and inflammation, today announced
results from the Phase II clinical trial of its lead compound M40403. The
trial demonstrated that the addition of M40403 to morphine improved the
analgesic profile of morphine in every measure of analgesic efficacy: faster
onset, longer duration, greater peak effect and greater overall effect.
Adding M40403 to a low dose of morphine produces a two- to three-fold increase
in the analgesic efficacy of the morphine without a concomitant increase in
morphine side effects.
The Phase II trial -- a randomized, double-blind, controlled, parallel
group study-- was conducted at two centers in Austin, Texas and Baltimore,
Maryland and enrolled 350 patients with moderate to severe pain following
dental surgery. Patients were randomized to receive one of three single
intravenous doses of morphine (0.04, 0.08, 0.12 mg/kg) alone or in combination
with 0.25 mg/kg M40403 or 0.25 mg/kg M40403 alone. Morphine was administered
over 10 minutes concomitantly with M40403 which was administered over 30
minutes.
"These results further support our assertion that SOD mimetics will be an
important part of the therapeutic approach to the management of pain," stated
Alan W. Dunton, M.D., President and Chief Executive Officer of Metaphore
Pharmaceuticals.
The following results were observed in the Phase II trial:
* Adding M40403 to morphine appeared to not only improve the overall
analgesic profile of morphine, but to make the dose response more
predictable.
* Median time to onset of analgesia in the M40403 plus 0.08 mg/kg
morphine group was 22.5 minutes compared to greater than 480 minutes in
the 0.08 mg/kg morphine alone group (p=0.0360).
* Median time to rescue medication in the M40403 plus 0.12 mg/kg morphine
group was 2.76 hours compared to 1.53 hours in the 0.12 mg/kg morphine
alone group (p=0.0153).
* Peak effect and overall effect, as measured by the peak pain intensity
difference (PPID) and the total pain relief (TOTPAR), were superior for
the combination of morphine and M40403 relative to morphine alone, and
a linear dose-response was observed in all measures when morphine was
combined with M40403.
* When M40403 was added to the lowest dose of morphine (0.04 mg/kg), the
pain relief measures over time were similar to the highest dose of
morphine (0.12 mpk) administered alone.
Furthermore, the mechanism of M40403 enhancing morphine is not a
mu-receptor interaction and appears to be limited to analgesia. There is no
pharmacokinetic interaction between M40403 and morphine or its metabolites.
Metaphore presented data at the Neuroscience 2003 Conference which
demonstrated that SOD Mimetics (SODm) are novel non narcotic analgesics. In
addition, preclinical animal model data showed that SODm synergistically
interacts with morphine to alleviate pain. These results were extended to
show that SODm prevented and reversed morphine tolerance. M40403 has been
independently tested by the National Institute on Drug Abuse and was found to
have no abuse liability. Metaphore plans to present and publish experimental
results detailing the mechanism of M40403's beneficial interaction with
opioids.
The potential target indication for M40403 is the treatment of cancer pain
and post-operative pain in patients in acute care settings who are on or are
candidates for opioid therapy.
In Metaphore's earlier Phase II trial, completed May 2003, the company
found that 20 mg of M40403 as a single agent was significantly superior to
placebo for up to one hour (p<0.05) following molar extraction. No serious
adverse events were reported. Results from the trial provided clinical proof
of concept that SOD mimetics are well-tolerated and have therapeutic
potential. Synergy with opioids has been observed in preclinical models,
which led to an analysis of response to opioid rescue medication in this
trial. Subjects receiving M40403 had an enhanced response to 5 mg hydrocodone
rescue medication, with an apparent dose-response related to the dose of
M40403 they had received. Based upon this clinical signal confirming a
preclinical finding, a randomized prospective trial was designed to
definitively test the hypothesis that M40403 could selectively enhance the
analgesic effect of opioids.
Further development is ongoing with a Phase II M40403 clinical trial
scheduled for the second quarter of 2004 in a bunionectomy pain model.
More about the Company
Metaphore Pharmaceuticals is a privately held biotechnology company which
discovers, develops and will market drugs that prevent and treat
inflammatory/autoimmune diseases and disorders, and pain. The company
leverages its expertise in chemistry and biology to discover and develop small
molecule compounds that mimic the activity of human enzymes. Metaphore's lead
compounds mimic the function of superoxide dismutase (SOD), a beneficial
enzyme that serves an important protective role in the body by removing
superoxide, a toxic free radical that can damage cells and tissues.
Superoxide anions are implicated in a variety of diseases associated with pain
and inflammation.
Metaphore has a global, multilayered intellectual property estate covering
its broad class of compounds including composition of matter and use patents.
This IP estate includes 31 issued and 39 pending worldwide patents.
Product candidates in U.S. clinical testing have broad therapeutic
potential across a variety of diseases. Metaphore currently focuses its
clinical development efforts in pain, rheumatoid arthritis and inflammatory
disorders. These markets are significant in terms of scope and size. The
company maintains offices in Fort Lee, New Jersey and St. Louis, Missouri. For
more information on Metaphore, please visit the Web site at:
metaphore.com.
This press release contains forward-looking statements based on
information available to Metaphore as of the date hereof. In some cases, you
can identify these forward-looking statements by the use of words such as
"may," "could," "expect," "intend," "plan," "seek," "anticipate," "believe,"
"estimate," "predict," "potential," "continue," or the negative of these terms
or other comparable terminology. Metaphore's actual results could differ
materially from the results stated or implied by such forward-looking
statements due to a number of risks and uncertainties. These risks and
uncertainties include, but are not limited to, general economic and business
conditions, changes in governmental laws and regulations relating to the
development and commercialization of pharmaceutical products, and competition
in our industry. In addition, we are developing several products for
potential future marketing. There can be no assurance that such development
efforts will succeed, that such products will receive required regulatory
clearance or that, even if such regulatory clearance were received, such
products would ultimately achieve commercial success. Metaphore disclaims any
intention or obligation to update or revise any forward-looking statements,
whether as a result of new information, future events or otherwise. |
