Ruzurgi (amifampridine) for Lambert-Eaton myasthenic syndrome

Last updated July 10, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD

What is Ruzurgi for Lambert-Eaton myasthenic syndrome?

Ruzurgi (amifampridine) is an oral medication used to improve muscle strength in people with Lambert-Eaton myasthenic syndrome (LEMS).

Although Ruzurgi was previously approved in the U.S. for the symptomatic treatment of children ages 6 to less than 17 with LEMS, its approval was vacated in 2022 for violating the market exclusivity rights of Firdapse, a similar therapy with the same active ingredient. Shortly afterward, the U.S. rights to Ruzurgi were acquired by Catalyst Pharmaceuticals, the company that sells Firdapse, as part of a settlement with Ruzurgi’s developer, Jacobus Pharmaceuticals.

Ruzurgi is approved and is currently available in Canada for treating LEMS in patients ages 6 and older. It is marketed by Médunik Canada and covered by most public health insurance programs in the country.

Its approval in Canada has also faced legal challenges from Catalyst, with the company arguing that the approvals illegally used data generated from studies of Firdapse. Ruzurgi’s approval was revoked in 2021, then quickly reinstated, but revoked again in 2022. Most recently, in early 2023, the Federal Court of Appeal of Canada ruled Ruzurgi’s approval was legal.

Therapy snapshot

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) 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 that lead to muscle contraction.

In 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 can increase the amount of acetylcholine released from nerve cell endings, thereby increasing muscle strength.

Who could take Ruzurgi?

Ruzurgi was approved by the U.S. Food and Drug Administration (FDA) for the symptomatic treatment of children, ages 6 to less than 17, with LEMS in May 2019. With that decision, Ruzurgi became the first LEMS therapy to be approved for that patient population. Its approval, however, has since been revoked and Ruzurgi is no longer available in the U.S.

In Canada, Ruzurgi was originally approved to treat LEMS patients, ages 6 and older, in August 2020. Although its approval in Canada has also been contested, the most recent federal court decision ruled the therapy’s approval in the country was valid.

Who should not take Ruzurgi?

Ruzurgi was contraindicated, or not recommended, for patients who’ve had allergic reactions to amifampridine, or other aminopyridines. The therapy also was contraindicated for patients with a history of seizures.

The safety and effectiveness of Ruzurgi for treating LEMS in children younger than 6 has not been established.

How was Ruzurgi administered?

Ruzurgi was administered in the form of oral tablets containing 10 mg of amifampridine. Tablets were oval and white to off-white in color, and were functionally scored to facilitate splitting into fractions. They were supplied in bottles.

Patients ages 6 to less than 17 and weighing at least 45 kilograms (about 99 pounds) were to start with 15 to 30 mg daily, in divided doses (two to three times daily). If needed, the medication’s total daily dosage could be increased by 5 to 10 mg daily, divided in up to five doses. The maximum single dose was 30 mg and the maximum daily dosage was 100 mg.

For those ages 6 to less than 17 but weighing less than 45 kg, Ruzurgi was initially given at 7.5 to 15 mg daily, in divided doses (two to three times daily). Ruzurgi’s total daily dosage could be increased by 2.5 to 5 mg daily, divided in up to five doses. The maximum single dose was 15 mg and the maximum daily dosage was 50 mg.

In pediatric 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 have been the lowest initial recommended daily dosage on each group — 15 mg daily for patients weighing 45 kg or more, and 7.5 mg daily for those weighing less than 45 kg.

Ruzurgi could be taken with or without food. If a dose was missed, patients should not take double or additional doses to compensate for the missed one.

A suspension of 1 mg/mL could be prepared and administered by mouth or feeding tube to patients who had difficulty swallowing tablets, or required assisted feeding or small dosage increments (less than 5 mg).

A similar dosing schedule is recommended for LEMS patients in Canada.

Ruzurgi in clinical trials

Ruzurgi’s approval 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).

DAPPER trial

DAPPER 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 to 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 (3 meters), and return to the chair three times without pause, as measured by the Triple Timed Up and Go test (3TUG).

Results showed that patients who remained on Ruzurgi had fewer impairments when performing these tasks compared with those who switched to the placebo. Specifically, while 72% of patients treated with a placebo saw their 3TUG scores deteriorate by more than 30% in the final test, none of those who continued with Ruzurgi saw that happen. Also, the patients who switched to the placebo reported a greater feeling of muscle weakness than those who remained on Ruzurgi.

Common side effects of Ruzurgi

Common side effects associated with Ruzurgi included:

• numbness or tingling sensation
• discomfort with sense of touch
• abdominal pain
• indigestion
• dizziness
• nausea.

Seizures

Patients may have experienced seizures while on Ruzurgi, including those without a history of such episodes. In those cases, patients were recommended to stop taking the medication or lower its dosage.

Allergic reactions

No allergic reactions, including anaphylaxis — a serious and potentially life-threatening allergic reaction — have been reported with Ruzurgi in clinical trials. However, anaphylaxis has been reported in patients taking other aminopyridines, indicating these serious allergic reactions might also occur with Ruzurgi. In such cases, the medication should have been stopped and appropriate treatment administered.

Use with other medications

People who took Ruzurgi alongside anti-seizure medications were more likely to have seizures. The therapy’s simultaneous use with cholinesterase inhibitors, a group of medicines that block the normal breakdown of acetylcholine, may have increased the cholinergic effects of Ruzurgi and of those medicines, and increased the risk of side effects.

Use in pregnancy and breastfeeding

It was unknown if Ruzurgi could affect a developing fetus or pass to breast milk. Patients planning to become pregnant or breastfeed should have talked with their healthcare team and only continue treatment during these periods if the potential benefits justified the potential risks to the fetus or infant.

Lambert-Eaton News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.