Last updated March 23, 2022, by Teresa Carvalho, MS
Fact-checked by Joana Carvalho, PhD
Ruzurgi (amifampridine, also called 3,4-diaminopyridine or 3,4-DAP), developed by Jacobus Pharmaceutical, was the first treatment approved by the U.S. Food and Drug Administration (FDA) for children, ages 6 to 16, with Lambert-Eaton myasthenic syndrome (LEMS).
In February 2022, its approval in the U.S. was canceled for violating market exclusivity rights of Firdapse, a similar therapy with the same active ingredient and which was previously approved for adults with LEMS.
In March 2022, Ruzurgi’s approval in Canada was suspended for the second time.
How does Ruzurgi work?
LEMS is a rare autoimmune disease in which the immune system generates autoantibodies against a protein called voltage-gated calcium channel (VGCC) found in nerve cell endings. Calcium channels are required for the release of acetylcholine, a neurotransmitter or cell signaling molecule, that initiates a cascade of events leading to muscle contraction.
In patients with LEMS, little acetylcholine is released in response to nerve signals. Without sufficient acetylcholine to promote muscle contraction, muscles tend to weaken over time and patients become easily fatigued.
Amifampridine, Ruzurgi’s active ingredient, binds to voltage-gated potassium channels. By blocking these channels, Ruzurgi prevents nerve cells from resetting after a nerve signal has been sent, giving more time for the small number of healthy VGCCs that remain to stay open. This in turn can increase the amount of acetylcholine that is released from nerve cell endings, and thereby increase muscle strength.
Ruzurgi in clinical trials
The decision to approve Ruzurgi for children and adolescents with LEMS was originally based on clinical data collected from adult patients, combined with simulations to find the best dose for children. Data were collected from a Phase 2 trial called DAPPER (NCT01511978).
The trial included 32 adults with LEMS who had been taking Ruzurgi for at least three months as part of an FDA-approved compassionate use program. Patients were randomly assigned to continue treatment with Ruzurgi at a daily dose of 30–100 mg (divided into three doses), or to a placebo.
The trial evaluated changes in the time it takes for a patient to rise from a chair, walk a short distance, and return to the chair three times without pause. Results showed that patients who remained on Ruzurgi experienced fewer impairments when performing these tasks compared with those who switched to the placebo. Additionally, patients who switched to the placebo reported a greater feeling of muscle weakness compared with those who remained on Ruzurgi.
Ruzurgi is an oral treatment available in tablets containing 10 mg of amifampridine.
Patients 6 and older and weighing at least 45 kg (about 99 lbs) are to start with 10 to 20 mg daily, in divided doses (two to three times daily). The maximum single dose is 20 mg and the maximum daily dosage is 80 mg, although some patients may benefit from a total daily dose of 100 mg.
For patients 6 and older but weigh less than 45 kg, they should begin with 5 to 10 mg daily, in divided doses (two to three times daily). The maximum single dose is 10 mg and the maximum daily dosage is 40 mg.
A suspension of 1 mg/mL can be prepared and administered by mouth or feeding tube to patients who have difficulty swallowing, or require feeding tubes.
Treatment may cause serious side effects, including seizures and allergic reactions. The most common side effects associated with Ruzurgi include abdominal pain, indigestion, dizziness, and nausea.
Ruzurgi is contraindicated, or not recommended, for patients who have had allergic reactions to the treatment or to any of its ingredients. People who have had a seizure should not take Ruzurgi. The therapy is also contraindicated for patients taking other forms of amifampridine or other aminopyridines.
The therapy should be cautiously used by patients with other conditions, such as liver disease, heart problems, and kidney failure.
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