Date: 2015-04-14
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Academy of Neurology (AAN) 67th Annual Meeting
Company: Catalyst Pharmaceutical Partners (USA - FL)
Product: Firdapse™ (amifampridine phosphate or 3,4-diaminopyridine (3,4-DAP) phosphate)
Action
mechanism: potassium channel inhibitor. Firdapse™, amifampridine phosphate or 3,4-diaminopyridine (3,4-DAP) phosphate, is a potassium channel inhibitor. By blocking this ion channel, Firdapse™ increases the nerve repolarization time, which causes an increase in the influx of calcium, thereby causing more acetylcholine to be released, which restores muscle fiber contraction, thus relieving muscle weakness caused by LEMS. In addition to LEMS, other potential orphan neuromuscular indications for Firdapse™ include certain types of Myasthenia Gravis and Congenital Myasthenic Syndrome, among others.
Firdapse™ has been granted orphan drug and breakthrough therapy designations by the FDA, and orphan medicinal product designation in the European Union for the treatment of LEMS. It is approved and commercialized in the E.U. by BioMarin Pharmaceutical. Upon completion of the Phase 3 trial, assuming the data from the trial is positive, Catalyst expects to begin submitting a rolling new drug application to the FDA in 2015.
Disease: Lambert-Eaton Myasthenic Syndrome (LEMS)
Therapeutic area: Autoimmune diseases - Neuromuscular diseases - Rare diseases
Country: USA, France, Germany, Hungary, Poland, Russian Federation, Serbia, Spain
Trial
details: The primary endpoint of the Phase 3 trial is a comparison of changes in patients randomized to continue Firdapse™ versus those who transition to placebo that occur in both the QMG score, which measures muscle strength, and subject global impression score, on which the subject rates their global impression of the effects of a study treatment during a 14-day double-blind efficacy evaluation period. The secondary endpoints are change in the investigator\'s assessment of worsening of disease symptoms and changes in walking speed (Timed 25-foot walking test) during the two-week, double-blind testing period. (NCT01377922). The Firdapse™ Phase 3 trial utilizes a randomized, double-blind, placebo-controlled, discontinuation design. The trial is being conducted at sites inthe United States and Europe. Following enrollment, patients were treated with open label drug for a minimum of 91 days, and then randomized to either continue on Firdapse™ or be discontinued to placebo over a 2-week period. Following the randomization phase of the trial, patients were then eligible to receive open label Firdapse™ treatment for a two-year follow-up period, to obtain additional long term safety data.
Latest
news: * On April 14, 2015, Catalyst Pharmaceutical Partners announced that Shin Oh, MD, one of its clinical investigators, will be making an oral presentation of safety and efficacy data from the Firdapse® Phase 3 clinical trial in patients with Lambert-Eaton myasthenic syndrome (LEMS) at the American Academy of Neurology (AAN) 67th Annual Meeting. The AAN meeting will be held April 18 to 25, 2015, in Washington, DC. The oral presentation is titled, "Amifampridine phosphate (Firdapse®) is safe and effective in a pivotal Phase 3 trial in LEMS patients" * On February 2, 2015, Catalyst Pharmaceutical Partners announced it has held a productive pre-New Drug Application (NDA) meeting with the FDA regarding Firdapse™ for the treatment of LEMS. Based on this meeting, Catalyst believes that its Phase 3 clinical program will provide acceptable support for submission of an NDA for Firdapse™ for LEMS. The Company plans to complete a full NDA submission during the 3rd quarter of 2015. Catalyst will confirm the overall regulatory path forward upon receipt of formal meeting minutes from the FDA in the coming weeks and will provide a further update at that time. * On October 8, 2014, Catalyst Pharmaceutical announced that Douglas Winship, Vice President of Regulatory Operations, will present top-line safety and efficacy results from Catalyst's Phase 3 Firdapse™ trial at the 139th Annual Meeting of the American Neurological Association being held at The Baltimore Waterfront Marriott, October 12-14. The presentation is entitled, "A Phase 3 Trial of Firdapse™ Tablets in Lambert-Eaton Myasthenic Syndrome. * On September 29, 2014, Catalyst Pharmaceutical Partners announced positive top-line results from the pivotal Phase 3 clinical trial of Firdapse™ (amifampridine phosphate tablets equivalent to 10 mg amifampridine) for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS). Both co-primary endpoints, quantitative myasthenia gravis score (QMG) and subject global impression (SGI), demonstrated that Firdapse™ was significantly superior to placebo, as did a secondary endpoint for the physician's clinical global impression of improvement (CGI-I). This clinical trial was designed as a double blind, randomized, "withdrawal trial" in which all patients were initially treated with Firdapse during a 91 day run-in period followed by treatment with either Firdapse or placebo (randomly assigned, about 1:1) during a 2 week randomization period. A total of 38 patients completed the 3 month run-in period and subsequent 2 week randomization period. In a trial of this design, the clinically significant findings, when present, are worsening of symptoms in the placebo group. Summary of Clinical Trial Results for Firdapse * On August 11, 2014, Catalyst Pharmaceutical Partners provided an update on the progress of its Phase 3 study of Firdapse™ (amifampridine phosphate) for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS). The last patient has completed the blinded portion of the study and top-line data remains on track to be reported later this quarter. A total of 38 patients completed the 3 month treatment period and were successfully randomized to either receive Firdapse™ or placebo. All patients who were randomized elected to continue in 2-year open label follow-up. If the company obtains positive results from its Phase 3 study, the company intends to submit a request to the FDA for a pre-NDA meeting and to initiate the steps necessary to seek regulatory approval of Firdapse™. This would likely include the initiation of a rolling NDA submission to the FDA by early-2015. Following enrollment, patients were treated with open label drug for a minimum of 91 days, and then randomized to either continue on Firdapse™ or be discontinued to placebo over a 2-week period. Following the randomization phase of the trial, patients were then eligible to receive open label FirdapseTM treatment for a two-year follow-up period, to obtain additional long term safety data. • Thirty eight (38) patients were successfully randomized into the 2-week, randomized, double-blind, placebo-controlled, discontinuation part of the study. The original target was to randomize 36 patients • All 38 randomized subjects elected to continue to receive Firdapse™ treatment in the 2-year, open label follow-up part of the trial. The company now plans to meet with the FDA in the fourth quarter to determine the fastest registration pathway.
• Primary endpoints
o The primary endpoint of change in quantitative myasthenia gravis score, or QMG, at day 14 reached statistical significance (p=0.0452) with a clinically significant worsening of 2.2 points observed in the placebo group.
o The primary endpoint of change in subject global impression, or SGI, at day 14 was highly statistically significant (p=0.0028) with a clinically significant worsening of 2.6 points observed in the placebo group.
• Secondary endpoints
o The secondary endpoint for the physician's clinical global impression of improvement, or CGI-I, reached statistical significance (p=0.0267) with a clinically significant observation at day 14 of 4.7 points in the placebo group.
o The secondary endpoint of change in walking speed at day 14 showed a worsening of 9.67 ft/min in the placebo group. As expected, this was a quantitative worsening in walking speed in the placebo group, but the magnitude of the change relative to the variance inherent in this test prevented reaching statistical significance for this endpoint with this small sample size.
• Patient tolerance of Firdapse
o Firdapse was generally safe and well tolerated.
o All subjects who were randomized into the trial elected to continue with Firdapse in the safety follow-up phase of the study.
