The FDA has granted approval to amifampridine (Ruzurgi, Jacobus Pharmaceuticals) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) for patients aged 6 to 17 years of age.1

The tablets are the first approved therapy specifically indicated for the treatment of pediatric patients with LEMS, a rare autoimmune disorder with neuromuscular symptoms caused by affected nerve connections and muscle weakness. The prevalence of LEMS in pediatric patients is unknown, but the estimated overall prevalence worldwide is 3 per 1 million individuals.

“We continue to be committed to facilitating the development and approval of treatments for rare diseases, particularly those in children,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. “This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities.”

Amifampridine was previously granted both priority review and fast track designations, as well as an orphan drug designation by the FDA due to the need for treatments for LEMS.

The agency’s go-ahead was granted based on data from a randomized, double-blind, placebo-controlled trial in adult patients with LEMS, as well as pharmacokinetic data and modeling in order to determine the best dosing regimen for pediatric patients. Those data also included safety information for pediatric patients with LEMS in the indicated age range.

Ultimately, the trial included 32 adult patients with LEMS who had been taking amifampridine for ≥3 months prior to the study period, at which point they were randomized to either remain on treatment or be switched placebo. The patients who continued on the therapy showed less impairment than those on placebo, with measurement assessed by the time it took the patients to rise from a chair, walk 3 m, and return to the chair for 3 consecutive laps without pause. A self-assessment scale was also utilized, with greater perceived weakening reported by patients on placebo.

The most common adverse events (AEs) experienced by pediatric and adult patients taking the study drug were paresthesia, abdominal pain, indigestion, dizziness, and nausea, with AEs reported in pediatric patients similar to those in adult patients. Notably, seizures were observed in patients without a history of seizures, and as such, the FDA stated that “patients should inform their health care professional immediately if they have signs of hypersensitivity reactions such as rash, hives, itching, fever, swelling or trouble breathing.”

Other literature has shown that amifampridine phosphate (Firdapse, Catalyst Pharmaceuticals) is effective in adults with LEMS. The Catalyst Pharmaceuticals formulation of the therapy is the only FDA-approved medicine for adults in this syndrome.

In a recently published study of the Catalyst product in 26 adults with LEMS,  amifampridine (n = 13) demonstrated a significant benefit in quantitative myasthenia gravis (QMG) score and subject global impression compared with placebo (n = 13) at the 4-day mark. Other measures of efficacy, including Clinical Global Impression-Improvement, 3TUG, and QMG limb domain score also improved. The most common AEs in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as anticipated from amifampridine withdrawal. Back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in only the amifampridine phosphate group.2
1. FDA approves first treatment for children with Lambert-Eaton myasthenic syndrome, a rare autoimmune disorder [press release]. May 6, 2019. Accessed May 13, 2019.
2. Sheih P, Sharma K, Kohrman B, Oh SJ. Amifampridine Phosphate (Firdapse) Is Effective in a Confirmatory Phase 3 Clinical Trial in LEMS. J Clin Neuromuscul Dis. 2019;20(3):111-119. doi: 10.1097/CND.0000000000000239.