A new phase 2, randomized, double-blind, and placebo-controlled study has offered Class II evidence of the safety and efficacy of amifampridine in patients with spinal muscular atrophy (SMA) type 3.

The study, published in the Journal of Neurology, showed statistically significant improvements in the Hammersmith Functional Motor Score Expanded (HFMSE) among the patients, but no notable improvements in secondary outcomes.

Amifampridine was well tolerated by all the patients, with no severe adverse events or treatment discontinuations due to adverse events.

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“In the SMA-001 trial, we aimed to evaluate whether fostering neuromuscular transmission could improve fatigability and motor function in SMA patients,” the authors wrote. “Hence, we assessed the safety and efficacy of amifampridine in ambulatory patients with SMA Type 3, not receiving other disease-modifying therapies.”

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Amifampridine is “a voltage-dependent K+ channel blocker that prolongs depolarization of the presynaptic neuromuscular junction terminal and increases acetylcholine release, empowering neuromuscular transmission and muscle function,” the authors wrote.

The research team conducted the phase 2a trial from January 2019 to September 2020 in Europe with 13 adult patients with genetically confirmed SMA type 3 who were not undergoing treatment with nusinersen. Initially, all patients received amifampridine orally at doses up to 80 mg per day. When patients achieved an improvement of at least 3 points on the HFMSE, the dose was considered effective.

Then, patients were randomized to receive amifampridine or placebo for 2 weeks, with the main outcome measure change from baseline in HFMSE scores and secondary outcomes being 6-min walk test (6MWT) times and various additional motor function times.

The patients receiving amifampridine had statistically significant increases in HFMSE scores compared with those taking placebo, but the authors note that the clinical difference was not significant and secondary outcome measures did not change. Therefore, larger well-powered studies are warranted to better elucidate the role of amifampridine as a treatment for patients with SMA.


Bonanno S, Giossi R, Zanin R, et al. Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial. J Neurol. Published online June 28, 2022. doi.10.1007/s00415-022-11231-7