Amifampridine phosphate (Firdapse(®)) is effective and safe in a phase 3 clinical trial in LEMS

Muscle Nerve. 2016 May;53(5):717-25. doi: 10.1002/mus.25070. Epub 2016 Mar 3.

Abstract

Objective: We evaluated the efficacy and safety of amifampridine phosphate (Firdapse(®)) for symptomatic treatment in Lambert-Eaton myasthenic syndrome (LEMS).

Methods: Phase 3, randomized, double-blind, study. Patients were treated initially with amifampridine phosphate for 7-91 days, followed by randomization to continue amifampridine phosphate for 14 days or placebo (7-day taper, 7-day placebo). The primary efficacy endpoints were changes from baseline at day 14 in Quantitative Myasthenia Gravis and Subject Global Impression scores.

Results: The coprimary efficacy end points and 1 of the secondary efficacy end points were met, showing a significant benefit of aminfampridine phosphate over placebo at Day 14. All 5 primary, secondary, and tertiary endpoints achieved statistical significance at Day 8. Amifampridine phosphate was well tolerated; the most common adverse events were oral and digital paresthesias, nausea, and headache.

Conclusions: This study provides Class I evidence of efficacy of amifampridine phosphate as a symptomatic treatment for LEMS.

Keywords: 3,4-DAP; 3,4-diaminopyridine; Amifampridine phosphate; LEMS; Lambert-Eaton myasthenic syndrome; Potassium channel blockers; Small cell lung cancer (SCLC).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • 4-Aminopyridine / analogs & derivatives*
  • 4-Aminopyridine / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Amifampridine
  • Calcium Channels / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Lambert-Eaton Myasthenic Syndrome / drug therapy*
  • Lambert-Eaton Myasthenic Syndrome / immunology
  • Male
  • Middle Aged
  • Muscle Strength*
  • Phosphates / therapeutic use*
  • Potassium Channel Blockers / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Calcium Channels
  • Phosphates
  • Potassium Channel Blockers
  • 4-Aminopyridine
  • Amifampridine