Amifampridine phosphate (FirdapseTM) is safe and effective in a pivotal Phase 3 trial in LEMS patients. (PL2.001)

Objectives: To evaluate the efficacy and safety of amifampridine (3,4-DAP) phosphate (FirdapseTM) as a symptomatic treatment for patients with Lambert-Eaton Myasthenic Syndrome (LEMS), in a Phase 3, multicenter, double-blind, placebo-controlled, randomized discontinuation study. Background: LEMS is a rare autoimmune disease. The primary symptom is proximal muscle weakness and easy fatigability_the result of autoantibodies to voltage-gated calcium channels, causing a reduction in the amount of acetylcholine (ACh) released from nerve terminals. Symptoms can be life threatening when the weakness involves respiratory muscles. Currently, there is no FDA approved drug for symptomatic treatment of this rare disorder. Design/Method: A Phase 3, multicenter, double-blind, placebo-controlled, randomized discontinuation study. For the efficacy assessment, primary endpoints were QMG score,a quantitative exam of muscle strength, and Subjective Global Impression (SGI). Secondary endpoints were Clinical Global Impression-Improvement (CGI-I) and Timed 25-Foot Walk test (T25FW). Results: 38 patients at 14 sites were randomized in this study: 16 to Firdapse TM and 22 to placebo. Day 14 analysis was made. In OMG score, placebo patients had a greater (2.2) worsening compared with FirdapseTM (0.2) (P=0.0452). In SGI score, placebo patients had a greater worsening (-2.6) compared with FirdapseTM (-0.8) (P=0.0028). In CGI score, placebo patients who had a greater worsening (4.7) compared with Firdapse (3.8) (P=0.0267). No significant change in score in TWF-25 between two groups.(P>0.05). No serious adverse events attributable to the drug have occurred to date. Firdapse™ tablets were generally safe and well tolerated; side effects were benign, consisting of perioral and digital paresthesia, gastrointestinal disorders and infections. Conclusion: The treatment with FirdapseTM achieved statistical significance for both coprimary end-points and one of two secondary end-points. Long-term safety of Firdapse TM is being studied in an Expanded Access Program. Disclosure: Dr. Oh has nothing to disclose. Dr. Gorodetzky has received personal compensation for activities with Catalyst Pharmaceuticals as an employee. He is an employee of Catalyst,