General Information

Firdapse (amifampridine) is a potassium channel blocker.

Firdapse is specifically indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults.

Fiedapse is supplied as a tablet for oral administration. The recommended starting dosage is 15 mg to 30 mg daily, taken orally in divided doses (3 to 4 times daily). The dosage can be increased by 5 mg daily every 3 or 4 days. The maximum recommended total daily dosage is 80 mg. The maximum single dose is 20 mg. If a dose is missed, patients should not take double or extra doses.

Clinical Results

FDA Approval

The FDA approval of Firdapse was based on two randomized, double-blind, placebo-controlled discontinuation studies. A total of 64 adults (age 21 to 88 years) with LEMS were enrolled (Study 1 and Study 2). Patients were required to be on an adequate and stable dosage (30 to 80 mg daily) of amifampridine phosphate prior to entering the randomized discontinuation phases of both studies. The two co-primary measures of efficacy in both studies were the change from baseline to the end of the discontinuation period in the Quantitative Myasthenia Gravis (QMG) score and in the Subject Global Impression (SGI) score.

Study 1: After an initial open-label run-in phase, 38 patients were randomized in a double-blind fashion to either continue treatment with Firdapse (n=16) or to a downward titration to placebo (n=22) over 7 days. Following the downward titration period, patients remained on blinded Firdapse or placebo for 7 more days. Efficacy was assessed at Day 14 of the double-blind period. Patients were allowed to use stable dosages of peripherally acting cholinesterase inhibitors or oral immunosuppressants. Twenty-six percent of patients randomized to Firdapse were receiving cholinesterase inhibitors, versus 36% in the placebo group, and 28% of patients randomized to Firdapse were receiving oral immunosuppressant therapies, versus 34% in the placebo group. During the double-blind period (from Baseline to Day 14), the QMG scores tended to worsen in both treatment groups, but there was significantly greater worsening in the placebo group than in the Firdapse group. Similarly, the SGI score tended to worsen in both treatment groups during the double-blind period, but there was significantly greater worsening in the placebo group than in the Firdapse group. These results indicate that in Study 1, patients randomized to placebo had a significantly greater worsening of muscle weakness and of global impression of the effects of the study treatment on their physical well-being, compared to patients who continued Firdapse in the double-blind period.

Study 2: Patients on stable treatment with Firdapse were randomized 1:1 in a double-blind fashion to either continue treatment with Firdapse (n=13) or change to placebo (n=13) for 4 days. Efficacy was assessed at the end of the 4-day double-blind discontinuation period. Patients were allowed to use stable doses of peripherally acting cholinesterase inhibitors or corticosteroids. From Baseline to Day 4, there was significantly greater worsening in the QMG score in the placebo group than in the Firdapse group, and also significantly greater worsening in the SGI score in the placebo group than in the Firdapse group. These results indicate that in Study 2, patients randomized to placebo had a significantly greater worsening of muscle weakness and of global impression of the effects of the study treatment on their physical well-being, compared to patients who continued Firdapse in the double-blind period.