The U.S. Food and Drug Administration has approved Firdapse (amifampridine phosphate), developed by Catalyst Pharmaceuticals, for adults with Lambert-Eaton myasthenic syndrome (LEMS), making it the first approved therapy in the U.S. for the condition.
“There has been a long-standing need for a treatment for this rare disorder,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
LEMS is characterized by muscle weakness caused by a reduction in the amount of the neurotransmitter acetylcholine (ACh) released from nerve terminals.
Firdapse, a formulation of amifampridine phosphate administered as oral tablets, is a neuronal potassium channel blocker that leads to the opening of slow voltage-dependent calcium channels, allowing for an influx of calcium. The compound also induces the secretion of synaptic vesicles to release more ACh into the synaptic space, enhancing neuromuscular transmission and improving muscle function. Synapses are the junctions between two nerve cells that allow them to communicate.
Approval was based on results of two Phase 3 trials, LMS-002 and LMS-003, which showed the therapy’s effectiveness.
The first trial, LMS-002 (NCT01377922), was a double-blind, placebo-controlled, randomized, parallel-group study designed to evaluate the effectiveness and safety of Firdapse in LEMS patients. The trial recruited 38 adults with LEMS who were given a maximum single dose of 20 mg of Firdapse or a placebo three to four times per day for a total daily dose of 30-80 mg, for two weeks.
The second, LMS-003 (NCT02970162), was a multicenter, double-blind, placebo-controlled study, conducted in four parts to evaluate the effectiveness and safety of multiple doses of Firdapse in LEMS patients. It recruited 26 adults with LEMS who were randomly assigned to a four-day oral treatment with either 10 mg of Firdapse or a placebo three to four times per day for a daily total dose of 30-80 mg.
Positive top-line results showed that, among other benefits, treatment with Firdapse led to clinically relevant differences over a placebo in quantitative myasthenia gravis score — a 13-item physician-rated assessment of arm and leg strength, face and neck muscle performance, swallowing, speech, grip strength, forced respiration, and gaze.
Firdapse received the FDA’s breakthrough therapy designation, as well as orphan drug status, designations granted to therapies that have shown potential to treat a serious condition. In 2016, Catalyst submitted a new drug application to the FDA, which was refused, with the FDA ruling the application was not sufficiently complete and requesting additional information. It was then accepted in June with priority review status.
Firdapse is the only approved medication in Europe for the symptomatic treatment of adults with LEMS.