Catalyst Pharmaceuticals, Inc. (Catalyst) (Nasdaq:CPRX), a
biopharmaceutical company focused on developing and commercializing
innovative therapies for people with rare neuromuscular and
neurological diseases, today announced positive top-line results
from the investigator-sponsored trial evaluating Firdapse®
(Amifampridine Phosphate) as a treatment for myasthenia gravis
patients with anti-MuSK antibodies (MuSK-MG). MuSK-MG, is an
ultra-rare sub-population of myasthenia Gravis (MG) patients which
is a debilitating neuromuscular disease, and there are currently no
FDA approved therapies for this specific form of MG. Both of
the co-primary efficacy endpoints of change from baseline (CFB) in
total Quantitative Myasthenia Gravis (QMG) score (p=0.0003) and CFB
in total Myasthenia Gravis Activities of Daily Living (MG-ADL)
score (p=0.0006) were statistically and clinically significant in
this seven patient trial. Several secondary efficacy measures
also achieved statistical significance. Amifampridine
phosphate was well tolerated in this population of patients.
The study was conducted by a team of researchers
led by Renato Mantegazza, MD, Director, Department of
Neuroimmunology and Neuromuscular Diseases, Fondazione Istituto
Neurologico Carlo Besta in Milan, Italy, a major referral center
for MuSK-MG patients. The study was designed as a randomized
(1:1), double-blind, placebo-controlled, crossover, outpatient
study to evaluate the safety, tolerability and potential efficacy
of amifampridine phosphate in patients diagnosed with
MuSK-MG. Catalyst provided funding, study drug, and placebo
for this trial.
Dr. Mantegazza, the principal investigator of
this trial, stated, “Our prospective study evaluating amifampridine
phosphate for the symptomatic relief of antibody positive MuSK-MG
was statistically significant in demonstrating that it can be an
important treatment option. Not only are the results
statistically significant, but more importantly, there was a large
clinical benefit to the patients. Current treatments for
MuSK-MG patients are often inadequate and these patients often face
a lifetime of severe complications, including difficulty walking,
talking, swallowing, and breathing normally, and in some cases
their disease may be life-threatening and require hospitalization
and intensive care. Amifampridine phosphate may offer us an
effective treatment option. I look forward to the day when I
can use this drug in routine clinical practice of treating MuSK-MG
patients.”
Dr. Silvia Bonanno, one of the investigators
from the Istituto Neurologico Carlo Besta, is planning to present
these results at the 13th International Conference on Myasthenia
Gravis and Related Disorders in May, 2017 in New York City,
provided her abstract is accepted as a Hot Topic Short Talk.
This conference is organized by the Myasthenia Gravis Foundation of
America and the New York Academy of Sciences.
“These data announced today should allow us to
accelerate our MuSK-MG program over the coming months, as we expect
to consult with our external experts and regulatory agencies on a
pivotal clinical development plan,” said Patrick J. McEnany,
Catalyst’s Chief Executive Officer. “I would like to thank Dr.
Mantegazza, his associates at Carlo Besta Neurological Institute,
and the patients that participated in this important clinical
trial.”
"While several effective treatment options exist
for the anti-acetylcholine receptor form of myasthenia gravis
(AcHR-MG), MuSK-MG has been particularly refractory to current MG
treatment options and represents an unmet medical need in the MG
community of patients," stated Gary Ingenito MD, Ph.D., Catalyst's
Chief Medical Officer. Dr. Ingenito continued: "If the
significant clinical effect observed in this trial is reproduced in
a multicenter trial, amifampridine phosphate would, upon approval,
likely become the first line standard of care for MuSK-MG.
Based on these results we intend to discuss with FDA conducting a
registration trial in the United States evaluating amifampridine
phosphate for the symptomatic treatment of patients with
MuSK-MG."
About the Clinical Trial
The MuSK-MG “proof-of-concept” trial was a
randomized, double blind, placebo-controlled, single site,
outpatient, investigator-sponsored, clinical trial to evaluate the
safety and efficacy of amifampridine phosphate in myasthenia gravis
patients with a positive serological test for the anti-MuSK
antibodies (MuSK-MG). Catalyst provided the investigational
drug, placebo, and funding for this clinical trial.
Patients were enrolled into the trial and were
titrated to an effective dose of amifampridine phosphate for a
period of at least 4 weeks in a "run-in" phase of the trial.
Following achievement of a dosage that effectively managed the
patient's symptoms, the patients were randomized 1:1 into one of
two crossover treatment groups. There were three treatment
periods in this crossover design, referred to as a "switch-back"
crossover design, that enables both the determination of the effect
of the treatment as well as the correction of any "subjective
carryover" from earlier treatment periods into later treatment
periods. Carryover in crossover designs is a common concern
of regulatory agencies, and this design effectively corrects for
and eliminates the effects of carryover from the efficacy
assessments. Each treatment period lasted 1 week for a total
of treatment duration of 3 weeks alternating with either
amifampridine phosphate or placebo. The co-primary efficacy
endpoints of change from base (CFB) in total Quantitative
Myasthenia Gravis (QMG) score and CFB in total Myasthenia Gravis
Activities of Daily Living (MG-ADL) score at the 7th day of each
period were assessed using a mixed carryover effects statistical
model of Kunert and Stufken. Secondary endpoints consisted
of, in order, CFB in Myasthenia Gravis Composite (MGC) Score, CFB
in Neurological Institute Carlo Besta-Myasthenia Gravis (NICB-MG)
score, proportion of patients with a 2, or larger, point reduction
in MG-ADL, proportion of patients with a 3, or larger, reduction in
MGC, CFB in Myasthenia Gravis Quality of Life, 15 domain, (MG-QoL
15) score, and CFB in Fatigue Severity scale (FSS).
Catalyst's funding of this study included the use of a CRO, and
this study was run as a well-controlled trial suitable for
regulatory submission.
About MuSK Myasthenia
Gravis
About 15% of MG patients test negative for the
acetylcholine receptor antibody. These patients have seronegative
(SN) MG. Approximately 40-50% of these patients with SNMG (equating
to an estimate of approximately 4,500 patients in the United
States) test positive for the anti-MuSK antibody. MuSK is a protein
that is required for the maintenance of the neuromuscular junction
and patients with the anti-MuSK antibody are identified as having
MuSK-MG. MuSK-MG is a clinically distinguishable, more severe form
of MG. The disease is characterized by a predominance in females, a
prevalent involvement of cranial and bulbar muscles, high incidence
of respiratory crises and a resistance to treatment. Although many
patients with MuSK MG are presently treated with anticholinesterase
inhibitors or immunosuppressants, such patients do not generally
respond adequately to these treatments.
About Catalyst
Pharmaceuticals
Catalyst Pharmaceuticals is a biopharmaceutical
company focused on developing and commercializing innovative
therapies for people with rare debilitating diseases, including
Lambert-Eaton myasthenic syndrome (LEMS), congenital myasthenic
syndromes (CMS), MuSK myasthenia gravis and infantile spasms.
Firdapse® has received Breakthrough Therapy Designation from the
U.S. Food and Drug Administration (FDA) for the treatment of LEMS
and Orphan Drug Designation for LEMS, CMS and myasthenia gravis.
Firdapse is the first and only approved drug in Europe for
symptomatic treatment in adults with LEMS.
Catalyst is also developing CPP-115 to treat
refractory infantile spasms and possibly refractory Tourette's
Disorder. CPP-115 has been granted U.S. Orphan Drug Designation for
the treatment of infantile spasms by the FDA and has been granted
E.U. Orphan Medicinal Product Designation for the treatment of West
syndrome by the European Commission. In addition, Catalyst is
developing a generic version of Sabril® (vigabatrin).
Forward-Looking Statements
This press release contains forward-looking
statements. Forward-looking statements involve known and unknown
risks and uncertainties, which may cause Catalyst's actual results
in future periods to differ materially from forecasted results. A
number of factors, including whether the receipt of breakthrough
therapy designation for Firdapse will expedite the development and
review of Firdapse by the FDA or the likelihood that the product
will be found to be safe and effective, the timing of Catalyst's
second trial evaluating Firdapse for the treatment of LEMS and
whether the trial will be successful, whether Catalyst's
assumptions in its updated business plan will be accurate and the
impact of unanticipated events or delays in projected activities on
Catalyst's cash requirements and on Catalyst's ability to get to an
accepted NDA submission for Firdapse without the need for
additional funding, what clinical trials and studies will be
required before Catalyst can resubmit an NDA for Firdapse for the
treatment of CMS and whether any such required clinical trials and
studies will be successful, whether any NDA for Firdapse
resubmitted to the FDA will ever be accepted for filing, the
timing of any such NDA filing or acceptance, whether, if an NDA for
Firdapse is accepted for filing, such NDA will be given a priority
review by the FDA, whether any future trial evaluating Firdapse for
the treatment of MuSK-MG will be successful and whether Catalyst
can obtain the funding required to conduct such trial, whether
Firdapse will ever be approved for commercialization, whether
Catalyst will be the first company to receive approval for
amifampridine (3,4-DAP), giving it 5-year marketing exclusivity for
its product, whether CPP-115 will be determined to be safe for
humans, what additional testing will be required before CPP-115 is
"Phase 2 ready", whether CPP-115 will be determined to be effective
for the treatment of refractory infantile spasms or possibly
Tourette's Disorder, or for any other indications, whether Catalyst
can successfully design and complete a bioequivalence study of its
version of vigabatrin compared to Sabril that is acceptable to the
FDA, whether any such bioequivalence study the design of which is
acceptable to the FDA will be successful, whether any ANDA that
Catalyst submits for a generic version of Sabril will be accepted
for filing, whether any ANDA for Sabril accepted for filing by the
FDA will be approved (and the timing of any such approval), whether
any of Catalyst's product candidates will ever be approved for
commercialization or successfully commercialized, and those other
factors described in Catalyst's Annual Report on Form 10-K for the
fiscal year 2015 and its other filings with the U.S. Securities and
Exchange Commission (SEC), could adversely affect Catalyst. Copies
of Catalyst's filings with the SEC are available from the SEC, may
be found on Catalyst's website, or may be obtained upon request
from Catalyst. Catalyst does not undertake any obligation to update
the information contained herein, which speaks only as of this
date.
Investor Contact
Brian Korb
The Trout Group LLC
(646) 378-2923
bkorb@troutgroup.com
Media Contacts
David Schull
Russo Partners
(212) 845-4271
david.schull@russopartnersllc.com
Company Contact
Patrick J. McEnany
Catalyst Pharmaceuticals
Chief Executive Officer
(305) 529-2522
pmcenany@catalystpharma.com
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