Joseph Krueger submits:
Its first product, CPP-109, is a formulation of vigabatrin.
Vigabatrin has been marketed over the past decade by Sanofi-Aventis
(
SNY
) under the brand name Sabril, as a secondary treatment for adult
epilepsy and as a primary treatment for the management of infantile
spasms. Prior to just last year, Sabril® was not approved for any
uses in the U.S. The FDA has been hesitant to approve vigabatrin
for use in the U.S., citing concerns about reports of retinal
damage in patients.
This has been a hurdle for any new indications of vigabatrin.
However, in August 2009, the FDA approved two NDAs from Ovation
Pharmaceuticals (now Lundbeck (
HLUKY.PK
)) for Sabril for the treatment of infantile spasms and as add-on
therapy for adult patients with refractory complex partial
epileptic seizures.
This change in FDA policy has opened the window for continued
development of vigabatrin. Catalysts Pharmaceuticals version of
vigabatrin, CPP-109, has been granted "Fast Track" status by the
U.S. Food & Drug Administration ((
FDA
)) for the treatment of cocaine addiction. This indicates that the
FDA has recognized the potential for CPP-109 to make a significant
contribution towards treating addiction, without a safety blockade
vigabatrin has experienced in the past. This is because Catalyst
Pharmaceuticals has provided sufficient data that CPP-109 works
without the apparent retinal damage side effects typically
associated with vigabatrin. In fact, the National Institute on Drug
Abuse ((
NIDA
)) has proposed to give Catalyst nearly $10 million to conduct a
U.S. Phase II(b) clinical trial evaluating CPP-109. Certainly this
is a vote of confidence for a CPP-109.
CPP-109 and vigabatrin works by indirectly lowering the level of
dopamine in the brain; specifically, GABA - gamma-aminobutyric acid
- a neurotransmitter in the brain that inhibits the release of
dopamine. Normally, the release of dopamine in the brain causes the
"high" or exaggerated sense of pleasure associated with drug abuse.
GABA, however, is broken down by GABA transaminase (GABA-T).
Vigabatrin works by inhibiting GABA-T and consequently by
increasing the level of GABA. This then lowers the level of
dopamine and turns off the "high", and prevents drug use from being
pleasurable to the user.
Over the years, vigabatrin has shown success in early trials,
suggesting it might be effective against stimulant addiction.
Previous studies in established animal models of addiction,
involving both rats and primates, have shown that vigabatrin
interrupts the neural mechanisms essential for addiction. In
preclinical studies, vigabatrin prevented the characteristic
drug-seeking behavior of addicted animals. Three human trials of
vigabatrin have been completed in patients addicted to cocaine or
methamphetamine. Data from these three trials provide clinical
evidence of vigabatrin's potential as a safe and effective
treatment for patients with these addictions.
Unlike alcohol and heroin, cocaine and speed have proven
particularly resistant to treatment with other drugs designed to
diminish craving. Since there are no FDA-approved medications for
cocaine or methamphetamine addiction, current treatment strategy
centers on cognitive and behavioral approaches.
From NIDA's point of view, a drug that effectively reduced
craving in abstinent cocaine and methamphetamine addicts would
dramatically improve addiction treatment. From a pharmaceutical
company's point of view, it would open up a potentially large and
lucrative market. NIDA has been the major supportor of vigabatrin
trials, sponsoring two major development programs for vigabatrin
for the treatment of cocaine and/or methamphetamine addiction.
NIDA's bet on Catalyst's CPP-109 :
A Cooperative Research and Development Agreement ((
CRADA
)) is a legal agreement between a government entity and one or more
non-government parties, such as private industry and academia.
CRADAs offer both parties an opportunity to leverage each other's
resources when conducting mutually beneficial research and
development (R&D).
In 2007, prior to its acquisition by Lundbeck, Ovation
Pharmaceuticals signed a five-year CRADA with NIDA to study the use
of vigabatrin for the treatment of cocaine and methamphetamine
dependence. The U.S. Food and Drug Administration ((
FDA
)) has given Fast Track designation to vigabatrin. Under the CRADA,
NIDA and Lundbeck (Ovation) were to jointly design and implement
preclinical studies as well as clinical trials to assess the
efficacy and safety of vigabatrin in cocaine and methamphetamine
abusers. However, no direct funding by NIDA was provided, and no
developments from this collaboration have been reported since this
initial announcement. Lundbeck does not report a clinical
development program for Sabril in this indication. The completed
and ongoing trials for vigabatrin (NCT00506935, NCT00626834) are
run by NIDA, not Lundbeck. This collaboration seems to have
dissolved, as there have not been any clinical trials started nor
updates in years.
However, NIDA is proposing to actively support CPRX to conduct
its U.S. Phase II(b) clinical trial evaluating CPP-109 for the
treatment of cocaine addiction. Under the preliminary agreement,
NIDA will provide the most substantial resources for the estimated
$10 milllion cost of the trial. CPRX will contribute approximately
$2.5 million in costs (including study medication, patient
recruitment costs and certain trial expenses), and NIDA will supply
the rest.
Previous trials
Much of the research on vigabatrin to treat addiction has
emerged from work performed over the last 12 years at the
Brookhaven National Laboratory. Brookhaven holds various patents
relating to its research findings. Catalyst has obtained from
Brookhaven an exclusive worldwide license for nine patents in the
United States for all rights to use or sell vigabatrin for the
treatment of addiction to cocaine, methamphetamine, prescription
pain medications, heroin, nicotine and other addictive drugs. In
addition, Catalyst's license includes rights to Brookhaven's
foreign patents or patents pending in more than 30 countries.
Catalyst also acquired worldwide rights to a related patent held by
Northwestern University. Together, these patents place CPRX as the
leader using vigabatrin-based therapy to treat addiction and a
natural choice for NIDA to collaborate with.
Catayst has run previous trials studying CPP-109 (trials
NCT00527683, NCT00730522, and NCT00611130). However, in 2009
CPP-109 failed in a phase IIa trial for treatment for cocaine
addiction. The results demonstrated that the drug did not help
addicts stay cocaine-free. As a result, CPRX shares dropped from
the $2 range to an all time low of 39 cents. Despite this disaster,
Catalyst stated that it will continue to develop CPP-109 for the
treatment of cocaine and methamphetamine addiction.
After post-hoc analyses of CPP-109 levels in urine samples
collected during the study, Catalyst concluded that less than 40%
of the trial subjects were medication compliant (these are drug
addicts after all, self-compliance is difficult). As a result, the
study was inadequately powered to test the protocol-specified
efficacy hypothesis . When corrected for poor medication
compliance, the major metabolite of cocaine measured in urine
collected from subjects were consistently lower in the CPP-109
treatment group, (an objective measure of daily cocaine usage); and
the patients demonstrated 3.5 times reduction in cocaine usage days
(an objective measure of dependence severity).
This analysis makes the response ratios in these patients very
significant, despite the failure in the overall pooled trial
results (the results were published in The American Journal of
Psychiatry). Catalyst's decision to continue the development of the
drug for both indications was supported by a panel of experts who
met and agreed with the company's conclusion that there was
sufficient evidence of safety and efficacy to justify further
development of CPP-109. Catalyst presented this post-hoc analysis
to NIDA. NIDA supported this conclusion and as a result, has
proposed to fund the majority of the phase IIb trial for
CPP-109.
Catalyst's plans for CPP-109 and other follow up drugs :
Patrick J. McEnany, Chief Executive Officer of Catalyst,
stated,
There remains a tremendous unmet medical need for cocaine and
methamphetamine addicted patients, and we believe a safe and
effective patient-specific treatment may generate considerable
interest among regulatory authorities, patients, physicians,
investors and potential strategic partners. Our next step will be
to present our findings to NIDA, the investment community, and
potential strategic partners to obtain the funding to conduct
additional clinical trials. We remain optimistic about the
prospects for CPP-109 going forward and we are committed to
aggressively pursuing our two primary objectives: (i) the
continued development of CPP-109 towards a pivotal Phase III
trial; and (ii) completing a high-value partnership for the
CPP-109 program. With the addiction market potentially exceeding
$1 billion and growing, we believe CPP-109 is very competitively
positioned from a safety and efficacy perspective. As a
shareholder with a significant personal investment in the
Company, my interests are aligned with the interests and concerns
of every shareholder. I am deeply committed to building a
successful Company.
Patrick J. McEnany is bullish about Catalyst's future, as any
CEO should be, but there is great cause for his bullishness. With
approval for CPP-109 for the treatment of cocaine addiction, the
company would have a corner on the market-- a $1 billion corner. If
it can gain FDA approval for this indication, others are likely to
follow, given the general role of GABA aminotransferase in many
types of addictions. With the support of the FDA and NIDA, it seems
that Catalyst has the support it needs. When the company completes
the trial and shows the efficacy it saw in compliant patients in
the phase IIa trial; and CPP-109 is on the fast track to approval,
literally. Although NIDA support will end after completion of this
trial, it is obvious than any number of major pharmaceutical
companies would be willing to partner with CPRX to support at phase
III trial to gain approval. With a current PPS of about 80 cents
and market cap of $15 million, CPRX is a whole lot of bang for very
little buck.
In 2010, CPRX will focus on developing CPP-109 for cocaine
addiction. CPRX has stated that it believes that the Fast Track
status from the FDA for CPP-109 for cocaine addiction may
facilitate the regulatory approval process. Catalyst expects to
execute a clinical trial agreement with NIDA in the near future,
and to commence the trial in the summer of 2010. CPRX anticipates
that an approximately 200 patient trial will take 18 months to
complete. It will be conducted at eight leading addiction
facilities across the United States. The clinical trial is designed
to confirm the safety and efficacy of CPP-109 for the treatment of
cocaine addiction. If successful, Catalyst believes it will qualify
to be one of the adequate and well controlled trials to support
approval of an NDA by the FDA.
Pipeline
In addition to CPP-109, earlier this year Catalyst also revealed
the company's development plans for its novel drug CPP-115. CPP-115
will be tested for the treatment of epilepsy, including infantile
spasms, and addiction. CPP-115 is a compound in a new class of
therapies for a broad range of central nervous system illnesses
that could benefit from the inhibition of GABA aminotransferase.
CPP-115 has been shown to be at least 200 times more potent than
vigabatrin. The increased potency could enable the development of
superior or alternative dosage forms and routes of administration
compared with Sabril. It may also have superior specificity to GABA
aminotransferase and, possibly, a better side effects profile
compared to Sabril. CPP-115 and other CPRX are the only known drugs
currently in development having GABA aminotransferase inhibition as
their primary mode of action. Catalyst is also seeking to develop
additional therapies similar to CPP-115 for a broad range of
central nervous system illnesses that could benefit from the
inhibition of GABA aminotransferase.
Over the next year, Catalyst plans to advance the development of
CPP-115 by completing a series of non-clinical studies designed to
demonstrate critical safety and efficacy characteristics of
CPP-115. CPRX states that by the end of the third quarter of 2010,
most of the safety studies for CPP-115 are expected to be
completed. Furthermore, by the end of this year, Catalyst expects
to complete animal studies for screening of CPP-115 as a potential
treatment for both epilepsy and drug addiction. Catalyst presented
data for CPP-115 at the 2010 Epilepsy Pipeline Update Conference in
February.
Catalyst also announced last Friday that on April 16th, it will
discuss data from its phase II clinical trial to evaluate the
safety and efficacy of Catalyst's drug CPP-109 (Vigabatrin) for
treating cocaine dependence at the American Society of Addiction
Medicine's (
ASAM
) 41st Annual Medical-Scientific Conference in San Francisco, CA.
Dr. Somoza was the Coordinating Principal Investigator for the
trial and will discuss data from Catalyst's U.S. Phase II trial
evaluating CPP-109 to treat cocaine addiction.
For more information about the company and these events, go to
www.catalystpharma.com
/.
Disclosure:
I have no position in CPRX
See also
A New Approach to Hedge Fund Replication
on seekingalpha.com