Last updated Oct. 13, 2022, by Teresa Carvalho, MS
Fact-checked by Joana Carvalho, PhD
What is Firdapse for Lambert-Eaton myasthenic syndrome?
Firdapse (amifampridine) is an oral therapy for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS). The therapy works to improve muscle strength and mobility in adults and children with the autoimmune disease.
It is the only orally available treatment approved in the U.S. for LEMS symptoms.
The medication was originally developed by BioMarin Pharmaceutical, but its licensing rights in North America have belonged to Catalyst Pharmaceuticals since October 2012.
How does Firdapse work?
LEMS develops because the body makes autoantibodies against a protein, known as voltage-gated calcium channel (VGCC), that’s found on nerve cell endings. As a result, nerve cells are prevented 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, called voltage-dependent potassium channel, found on nerve cells. This causes any remaining healthy VGCCs to stay open, allowing for the influx of calcium ions into nerve cells. That potentially increases the amount of acetylcholine released from nerve cell endings, which in turn is expected to help enhance muscle strength.
Who can take Firdapse?
Firdapse is the first and only oral therapy available in the U.S. for the symptomatic treatment of LEMS. The U.S. Food and Drug Administration (FDA) approved the therapy in November 2018 for patients ages 17 and older.
That approval was expanded in October 2022 to include children as young as 6. The decision followed the cancelation of the regulatory approval of Ruzurgi, a therapy containing the same active agent as Firdapse. In the U.S., Ruzurgi had previously been approved to treat children and adolescents with LEMS.
In the EU, Firdapse was approved by the European Commission in 2009 for commercial use. In 2020, Canada’s regulatory agency also approved the use of Firdapse for the treatment of adults with LEMS. Catalyst also amended its license agreement for Firdapse in May 2019 to expand its commercial territory to Japan.
Who should not take Firdapse?
Firdapse is contraindicated, or not recommended, for people with a history of seizures and allergic reactions to amifampridine or similar organic compounds. The medication should be stopped if seizures or life-threatening allergic reactions occur.
How is Firdapse administered?
The therapy is available as tablets containing 10 mg of amifampridine. Tablets have a white to off-white color and a round shape, and are functionally scored to facilitate splitting into fractions.
The recommended starting dose for adults and children weighing 45 kg (around 99 pounds) or more is 15 to 30 mg daily, taken in divided doses three to four times daily. If needed, the medication’s dosage can be increased by 5 mg daily every three to four days. The maximum recommended dose is 80 mg per day.
For children weighing less than 45 kg, the recommended starting dose is 5 to 15 mg daily, also taken in divided doses. Firdapse’s dosage also can be increased by 2.5 mg daily every three to four days, if needed. The maximum recommended dose in these patients is 40 mg daily.
In patients with kidney or liver impairments, or in those who are known to process the medication’s active ingredient at a slower pace, the recommended starting dose should be the lowest initial recommended daily dosage on each group — 15 mg daily for adults and children weighing more than 45 kg, and 5 mg daily for children weighing less than 45 kg.
The medication can be taken with or without food, but pills cannot be chewed. Treatment is supplied both in bottles and blister packs that should be stored at room temperature.
Firdapse in clinical trials
Firdapse’s approval was based on positive results from two Phase 3 randomized, double-blind, placebo-controlled trials. In these trials, dubbed Study 1 and Study 2, neither the researchers nor the participants knew which patients were receiving Firdapse and which the placebo.
The first (NCT01377922) involved 38 LEMS patients. Changes from baseline, or the study’s start, were analyzed at day 14 for both the Firdapse and the placebo treatment 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 uses to grade a patient’s muscle weakness. The SGI score is 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, 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 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 extremities, or headaches, were noted in those being treated with Firdapse, whereas those given a placebo reported fatigue and muscle weakness, which was expected due to Firdapse withdrawal.
Common side effects of Firdapse
The most common side effects associated with Firdapse include:
- burning or prickling sensation in the arms, legs, hands, and feet.
- upper respiratory tract infection.
- abdominal pain.
- liver dysfunction.
- back pain.
- high blood pressure.
- muscle spasms.
Patients may experience seizures while on Firdapse — including those without a history of such episodes. If so, patients are recommended to stop taking the medication or reduce its dosage.
Firdapse may potentially cause allergic reactions, such as anaphylaxis, which can be serious and life-threatening and have been reported in patients taking similar organic compounds. In such cases, the medication should be stopped and appropriate treatment administered.
Use in pregnancy and breastfeeding
According to animal data, Firdapse may cause harm to a developing fetus. Therefore, patients who are pregnant or are planning to become pregnant should discuss this issue with their healthcare team. Patients who are breastfeeding or plan to breastfeed also should inform their healthcare provider, as it is not clear if Firdapse can pass into breast milk.
Pregnant women may enroll the Firdapse Pregnancy Registry, which was created to monitor pregnancy and newborn outcomes.
Use with other medications
People who take Firdapse alongside medicines used to treat seizures are more likely to experience side effects. The therapy’s simultaneous use with cholinesterase inhibitors — a group of medicines that block the normal breakdown of acetylcholine — may increase the cholinergic effects of Firdapse and of those medicines, and heighten the risk of side effects.
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