Catalyst plans early 2015 rolling NDA on Firdapse Phase III
This article was originally published in Scrip
Catalyst Pharmaceuticals plans to initiate a rolling new drug application (NDA) for Firdapse in early 2015, pending pre-NDA discussions with the US FDA, based on positive Phase III results in the treatment of Lambert-Eaton myasthenic syndrome (LEMS).
Coral Cables, Florida-based Catalyst jumped 19.7% to $3.58 per share after the market closed on 29 September following the disclosure that Firdapse achieved statistical significance versus placebo for both co-primary endpoints in the company's 38-patient Phase III clinical trial. Catalyst CEO Patrick McEnany told Scrip that the company plans to commercialize Firdapse – a proprietary formulation of an available therapy – with its own 15- to 20-member sales force.
Firdapse is Catalyst's own version of the potassium channel inhibitor amifampridine phosphate or 3,4-diaminopyridine (3,4-DAP) phosphate. Available versions of 3,4-DAP are not approved to treat LEMS in the US, but sometimes are prescribed off-label to patients with the ultra-rare neuromuscular disease that affects about 3,500 people in the US and Canada, which raises the specter of potentially lower cost competition for Firdapse from a handful of specialized compounding pharmacies.
Intravenous immunoglobulin (IVIG), plasmapheresis and steroids also have been used to treat LEMS, but Mr McEnany said those options tend to be less effective than 3,4-DAP.
The autoimmune disorder leads to muscle weakness primarily in the legs, thighs and hips of patients starting in their 40s and 50s, but the disease can become life-threatening if it leads to respiratory muscle weakness. LEMS patients also are prone to lung cancer.
Catalyst won orphan drug status for Firdapse in the US and 13 months ago the FDA granted a breakthrough therapy designation – a designation reserved for novel treatments for life-threatening diseases (scripintelligence.com, 28 August 2013).
Phase III results
All patients enrolled in Catalyst's Phase III clinical trial were treated with Firdapse for 91 days before they were randomized 1-to-1 to treatment with the drug or placebo for two weeks. All 38 patients completed the run-in and randomized portions of the trial and decided to participate in the company's two-year, open-label extension study.
See the table below for the top-line results at day 14 of the Phase III study's randomized period. The endpoints were dependent on a worsening of symptoms in the placebo arm of the study.
Endpoint | Decline in the placebo arm | P-value |
Change in quantitative myasthenia gravis (QMG) score (primary endpoint) | 2.2 points | P=0.0452 |
Change in subject global impression (SGI) score (primary endpoint) | 2.6 points | P=0.0028 |
Physician's clinical global impression (CGI-I) score (secondary endpoint) | The CGI-I score was 4.7 points in the placebo group, but the score was not provided for Firdapse, and the decline from the randomized period's baseline was not provided. | P=0.0267 |
Change in walking speed (secondary endpoint) | 9.67 feet per minute | Not statistically significant |
Firdapse was generally safe and well-tolerated. Mr McEnany noted that some mild gastrointestinal issues were observed during the study, but the most common side effect was paresthesia, or a tingling sensation in the fingertips.
More detailed results will be revealed in an oral presentation and a poster session at the American Neurological Association 2014 Annual Meeting from 12 to 14 October in Baltimore, Maryland. Phase III data also will be presented at the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting from 29 October to 1 November in Savannah, Georgia.
Plans for the future
"Now that we have this data in hand, we also expect to launch by mid-October our expanded access program (EAP)," Mr McEnany said. "It will allow us to build a database of physicians and patients who will be prescribers and users of our drug."
The EAP also will help the company establish a safety and efficacy database for its product candidate on top of prior clinical trial results and before potential FDA approval in early 2016.
Jacobus Pharmaceutical also has a proprietary formulation of 3,4-DAP in development for LEMS, although it is behind Firdapse in Phase II, but the company already provides its compound for free under an EAP. Catalyst announced plans for its own EAP earlier this year to provide Firdapse free of charge to patients who've participated in the company's studies and to other LEMS patients who'd like access to the drug (scripintelligence.com, 24 April 2014).
"We'll meet in the fourth quarter with the FDA and we'll have our pre-NDA meeting at that time," Mr McEnany said. "The FDA requested from us in December that as soon as our [data] modules are available that we begin a rolling NDA submission. Our first module will be ready to go into a rolling NDA submission in the first quarter of next year."
In preparation of an anticipated launch in early 2016, Catalyst has begun pre-commercialization activities, including a key senior executive hire and recruitment of a small sales and marketing team, the latter of which will start in the fourth quarter of this year.
The company also plans to develop Firdapse for the treatment of certain types of myasthenia gravis, including congenital myasthenia gravis syndrome (CMS). CMS affects 1,000 to 1,500 people in the US and Canada, two-thirds of whom are diagnosed under the age of 18.