WASHINGTON, DC—Amifampridine phosphate is a safe and effective symptomatic treatment for patients with Lambert-Eaton myasthenic syndrome (LEMS), according to Phase III data presented at the 67th Annual Meeting of the American Academy of Neurology. Compared with placebo, the drug may slow the decline in muscle strength associated with LEMS.
LEMS is a rare autoimmune disease that causes proximal muscle weakness, areflexia, and dysautonomic symptoms. Diagnosis often is based on a positive test for voltage-gated calcium-channel antibodies. No symptomatic treatment for LEMS has regulatory approval in the United States, and the most common treatments have limited efficacy and raise safety concerns.
Shin J. Oh, MD, Distinguished Professor Emeritus of Neurology at University of Alabama in Birmingham, and colleagues enrolled 38 patients with LEMS at 14 sites in a Phase III trial of amifampridine phosphate. After the investigators screened the patients, they conducted an open-label trial that lasted from seven to 90 days and adjusted the dose of the drug. Next, 16 participants were randomized to amifampridine phosphate, and 22 participants were randomized to placebo. In the last stage of the trial, all patients received the drug for a long-term safety analysis.
The study’s primary end points were changes in the Quantitative Myasthenia Gravis (QMG) score and Subjective Global Impression (SGI) score. Secondary end points were changes in the Clinical Global Impression-Improvement (CGI-I) and the Timed 25-Foot Walk test. The investigators analyzed their data on day 14 of the trial.
The two treatment groups’ demographic and disease characteristics were not significantly different. The researchers observed statistically significant differences in QMG and SGI scores between the treatment groups at day 14. QMG score decreased by 2.2 points in the placebo group, compared with a decrease of 0.4 in the active group. SGI score decreased by 2.6 points among controls, compared with a decrease of 0.8 points among patients receiving amifampridine phosphate.
The investigators also found a statistically significant difference in CGI scores between study groups at day 14. CGI scores decreased by 4.7 points for controls, compared with a decrease of 3.6 points for patients receiving amifampridine phosphate. Dr. Oh’s group found no statistically significant difference in Timed 25-Foot Walk test results between the groups.
Approximately 59% of the patients in the placebo group had rapid worsening of QMG score at day 8, compared with 6.3% of patients receiving amifampridine phosphate. In addition, 55% of controls had rapid worsening of SGI score at day 8, compared with 8.2% of participants in the active group. The researchers also observed rapid worsening of CGI score on day 8 in 55% of patients receiving placebo and 12.5% of patients receiving amifampridine phosphate.
Adverse events were minimal, according to Dr. Oh. About 53% of patients had upset stomach or tongue numbness, and 45% of patients had finger numbness. Approximately 13% of participants had minor infections such as sinusitis and sore throat. Two of the 18 patients receiving the study drug had headache.
—Erik Greb