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FDA Approves First Treatment for LEMS

— Novel drug slowed disease worsening in rare autoimmune neuromuscular disorder

MedpageToday

WASHINGTON -- The , the first treatment for the rare autoimmune disorder Lambert-Eaton myasthenic syndrome (LEMS), for adult patients late Wednesday.

LEMS is characterized by muscle weakness, often in the arms and legs, and is caused by an autoimmune reaction in which antibodies are formed against voltage-gated potassium channels, causing the amount of acetylcholine released by the nerves to be reduced. Symptoms can be life threatening when the weakness involves the respiratory muscles.

LEMS is associated closely with cancer, particularly small cell lung cancer, with onset preceding or coinciding with cancer diagnosis, and affects an estimated 3 per 1,000,000 people worldwide.

"There has been a long-standing need for a treatment for this rare disorder," Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, said in a statement announcing the approval. "Patients with LEMS have significant weakness and fatigue that can often cause great difficulties with daily activities."

Amifampridine blocks presynaptic potassium channels and subsequently increases presynaptic calcium concentrations and . It has been approved for LEMS in Europe since 2009, but its road to approval in the U.S. has been rocky. The FDA nod this week came after the second time drug maker, Catalyst Pharmaceuticals, submitted its application; after the first go-around in 2016, the beyond Catalyst's initial phase III trial data. Other than amifampridine, treatments may include immunosuppressants and pyridostigmine, although their efficacy is modest at best.

The FDA approval on Wednesday was based on two clinical trials that together included 64 adult patients who received amifampridine or placebo. In both Quantitative Myasthenia Gravis (a 13-item physician-rated scale assessing muscle weakness) and Subject Global Impression (a 7-point patient-rated scale) scores, amifampridine bested the placebo.

Side effects most commonly experienced by trial patients were burning or prickling sensations, upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension, and muscle spasms. Seizures were also observed in patients who did not have a history of seizures. Patients should inform their health care provider immediately if they have reactions like rash, hives, itching, fever, swelling, or trouble breathing, the FDA warned.

The FDA previously granted amifampridine priority review, breakthrough therapy, and orphan drug designations. The drug is expected to be in 10 mg tablets early next year.