Firdapse (Amifampridine)

Last updated March 4, 2022, by Teresa Carvalho, MS

✅ Fact-checked by Joana Carvalho, PhD


Firdapse (amifampridine) is the first and only oral therapy available in the U.S. for the symptomatic treatment of patients ages 17 and older with Lambert-Eaton myasthenic syndrome (LEMS).

The medication was originally developed by BioMarin Pharmaceutical and approved by the European Commission in 2009 for commercial use in Europe. Its licensing rights in North America have belonged to Catalyst Pharmaceuticals since October 2012.

The U.S. Food and Drug Administration (FDA) approved the therapy for use in adults with LEMS in November 2018. Catalyst also amended its license agreement for Firdapse in May 2019 to expand its commercial territory to Japan.

The company now is planning to request that the FDA extend Firdapse’s approval to children. That application follows the cancelation of regulatory approval for Ruzurgi, a therapy containing the same active agent as Firdapse, in the U.S. Ruzurgi had been approved to treat children and adolescents with LEMS.

How does Firdapse work?

LEMS develops because the body makes autoantibodies against a protein found on nerve cell endings, called voltage-gated calcium channel (VGCC). This prevents nerve cells from taking up calcium, which is required for the release of a neurotransmitter, or cell-signaling molecule, called acetylcholine.

Acetylcholine is normally released into the neuromuscular junction — the point where nerve and muscle cells come into contact — to trigger muscle contraction. In patients with LEMS, however, little acetylcholine is released, resulting in muscle weakness and fatigue.

Firdapse is a small molecule that non-specifically blocks another protein channel found on nerve cells, called voltage-dependent potassium channel. This causes any remaining healthy VGCCs to stay open, allowing for the influx of calcium ions into nerve cells. This potentially increases the amount of acetylcholine released from nerve cell endings, which in turn is expected to help enhance muscle strength.

Firdapse in clinical trials

Firdapse’s approval was based on positive results from two Phase 3 randomized, double-blind, placebo-controlled trials.

The first (NCT01377922) was conducted with 38 participants. Changes from baseline, or the study’s start, were analyzed at day 14 for both the Firdapse treatment and placebo groups. The study assessed changes in several measures, including quantitative myasthenia gravis (QMG) and subject global impression (SGI) scores. QMG is a 13-item scale a physician use to grade a patient’s muscle weakness. SGI score represents a seven-point scale in which patients rate the global impression of the effects of the study treatment on their overall well-being.

Other measures included the clinical global impression-improvement (CGI-I), a seven-point scale used by physicians to grade changes in patient symptoms, behavior, and functional abilities.

Although QMG and SGI scores tended to worsen in both groups, in patients given a placebo, the degree of worsening was significantly greater than that seen in those treated with Firdapse. Additionally, CGI-I scores were significantly higher in patients given a placebo, indicating that physicians perceived greater disease worsening in that group of patients compared with those treated with Firdapse.

The other trial (NCT02970162) involved 26 adults with LEMS and analyzed the efficacy of Firdapse over a four-day period. Participants were on a stable dose of Firdapse for at least one week before the study. After baseline measurements on day 0, the patients were randomly assigned to either continue treatment with Firdapse or receive a placebo from day 1 to day 3. They were then assessed after taking their medication on day 4.

Results showed significant benefits of Firdapse treatment over a placebo in all parameters analyzed, including CGI-I, QMG, and SGI scores. Mild adverse events or side effects, such as back pain, pain in the arms and legs, or headaches, were noted in those being treated with Firdapse, whereas those given a placebo reported some fatigue and muscle weakness, which was expected due to Firdapse withdrawal.

Other details

Firdapse is available as an oral tablet containing 10 mg of amifampridine. The recommended starting dosage is 15 to 30 mg daily, taken in divided doses (three to four times daily). Maximum recommended dose is 80 mg daily.

The most common side effects associated with Firdapse include a burning or prickling sensation in the arms, legs, hands, and feet, upper respiratory tract infection, abdominal pain, nausea, and diarrhea. Headache, liver dysfunction, back pain, high blood pressure, and muscle spasms also are common.

Firdapse is contraindicated, or not recommended, in people with a history of seizures and allergic reactions to amifampridine. The medication should be stopped if seizures or life-threatening allergic reactions occur.

People who take Firdapse alongside medicines used to treat seizures are more likely to develop these symptoms. The use of Firdapse with cholinesterase inhibitors — a group of medicines that block the normal breakdown of acetylcholine — may potentiate the cholinergic effects of Firdapse and of those medicines, and increase the risk of side effects.

 


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