Amifampridine Phosphate (Firdapse) Is Effective in a Confirmatory Phase 3 Clinical Trial in LEMS.

Abstract

OBJECTIVE:

To assess tolerability and efficacy of amifampridine phosphate versus placebo for symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS).

METHODS:

This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in 26 adults with LEMS compared efficacy of amifampridine phosphate versus placebo over a 4-day period. The primary endpoints were quantitative myasthenia gravis score (QMG) and subject global impression, and the secondary endpoint was Clinical Global Impression-Improvement. The exploratory endpoints were 3TUG (timed up and go) test and QMG limb domain score. All participants had been receiving amifampridine phosphate (30-80 mg/d divided into 3 or 4 doses daily) in an expanded access protocol and had been titrated to the optimal dose and frequency for at least 1 week before randomization into the current study. After completion of assessments after 4 days of double-blind treatment, patients had the option to return to open-label amifampridine phosphate. The efficacy endpoints were mean changes from baseline in the various evaluation parameters.

RESULTS:

Amifampridine phosphate (n = 13) demonstrated significant benefit in QMG and subject global impression compared with placebo (n = 13) at 4 days. Other measures of efficacy, including Clinical Global Impression-Improvement, 3TUG, and QMG limb domain score also improved. The most common "adverse events" in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as expected from withdrawal of amifampridine phosphate, whereas only back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in amifampridine phosphate group.

CONCLUSIONS:

This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in adults with LEMS provided class I evidence of efficacy of amifampridine phosphate as symptomatic treatment in LEMS.

• Authors: Perry Shieh, Khema Sharma, Bruce Kohrman, Shin J Oh
• Journal: Journal of clinical neuromuscular disease (J Clin Neuromuscul Dis) Vol. 20 Issue 3 Pg. 111-119 (Mar 2019) ISSN: 1537-1611 [Electronic] United States
• PMID: 30801481 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Neuromuscular Agents
• Amifampridine

Topics

• Adult
• Aged
• Amifampridine (therapeutic use)
• Double-Blind Method
• Female
• Humans
• Lambert-Eaton Myasthenic Syndrome (drug therapy)
• Male
• Middle Aged
• Neural Conduction (drug effects)
• Neuromuscular Agents (therapeutic use)
• Severity of Illness Index
• Treatment Outcome
• United States