Amifampridines are Safe and Effective for Managing LEMS Symptoms, Review Suggests

Amifampridine-based medications are the most effective and safest options for managing symptoms of Lambert-Eaton myasthenic syndrome (LEMS), and should be chosen as the first-line management therapy for the rare autoimmune disorder, a review proposes.

The study, “Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome,” was published in the Expert Review of Clinical Immunology.

The mainstay for symptomatic treatment of LEMS is 3,4-diaminopyridine (3,4-DAP). Due to issues with variability and reliability, 3,4-DAP was modified into a salt formulation called Firdapse (amifampridine phosphate).

Firdapse, developed by Catalyst Pharmaceuticals, is an oral prescription therapy for patients ages 17 and older for the symptomatic treatment of LEMS. It was approved by the U.S. Food and Drug Administration (FDA) less than a year ago in November 2018. The treatment restores the communication between muscle cells, improving patients’ muscle function.

In May, the FDA approved Ruzurgi (amifampridine) for the treatment of children ages 6–17 with LEMS, making it the only approved therapy for children with this condition.

Shin J. Oh, MD, an expert from the University of Alabama at Birmingham, reviewed all relevant literature on LEMS treatment, namely with aminopyridine and amifampridine.

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The therapeutic role of amifampridines, including 3,4-DAP and Firdapse, has been extensively studied in neuromuscular diseases such as LEMS and myasthenia gravis.

In several randomized and non-randomized clinical trials, amifampridines have been shown to be well tolerated, safe, and the most effective medication for the management of LEMS symptoms. “Because of short-acting drug effects, it should be given three or four times a day,” Oh writes.

Amifampridine-based treatment has been associated with an increased risk of seizures, but doses below 80 mg a day shouldn’t be problematic, according to Oh. The most common side effects of 3,4-DAP and Firdapse are gastrointestinal discomfort and digital and perioral numbness or tingling sensation (paresthesia).

In LEMS, the communication between muscle cells can be so compromised that patients may sometimes experience a worsening of symptoms to the point of myasthenic crises, where an extreme episode of weakness leads to respiratory failure. This episode is known as a LEMS crisis. Amifampridines have been proven to be the medication of choice and to save lives in a LEMS crisis scenario.

Amifampridines can also be safely used for long periods of time and supplemented with Mestinon (pyridostigmine) to further ease LEMS symptoms without troublesome adverse events.

Available evidence indicates amifampridines are safe and the most effective therapy for the management of LEMS symptoms. As such, “AFPs [amifampridines] should be the drug of choice for the symptomatic treatment in LEMS,” Oh concludes.