Phase 2b Trial Finds Firdapse Effective, Safe in Adults with MuSK-MG

Treatment of adult MuSK-antibody positive myasthenia gravis (MuSK-MG) patients with the investigational therapy Firdapse (amifampridine phosphate) improved muscle strength, eased fatigue, and was safe, according to full results of a Phase 2b clinical trial.

Recruitment is ongoing for a phase 3 clinical trial (NCT03579966) testing Firdapse in MuSK-MG patients.

The study, “Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study,” appeared in the journal SAGE Open Medicine.

MSK-001 was a double-blind, placebo-controlled trial conducted at the Istituto Neurologico Carlo Besta in Milan, Italy. The study — partially funded by Catalyst Pharmaceuticals — intended to evaluate the safety and efficacy of Firdapse as a treatment for people with MuSK-MG.

Ten patients were treated. All had Myasthenia Gravis Foundation of America class IIb–IVb — mild to severe forms of MG predominantly affecting bulbar muscles — and a score of 9 or more on the Myasthenia Gravis Composite scale. Researchers were initially planning to recruit 20 patients, but Firdapse’s beneficial effect on muscle strength and fatigue prompted them to stop enrollment at 10.

After an initial stage to find a tolerable and effective dosage within 30-100 mg per day, the patients were randomized to either a placebo-Firdapse-placebo or a Firdapse-placebo-Firdapse sequence daily for seven days. This was followed by two switches of treatment group for 21 days, a design that enables the recruitment of a small number of participants, the researchers noted.

Three patients were not randomized because they did not achieve a stable dose during the run-in period. The other seven had a mean age of 43.4 years at the study’s start and 37 years at disease onset. Six were women and five were already receiving treatments for MuSK-MG. The effective dose achieved during the initial phase was within 30-60 mg daily for all seven patients.

The primary goals were changes in the Quantitative Myasthenia Gravis (QMG) score and in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Secondary goals included assessments of quality of life (using the Myasthenia Gravis Quality of Life scale) and fatigue (using the Fatigue Severity Scale).

Treatment with Firdapse led to statistically significant changes in both QMG and MG-ALD scores, as well as in all patient- and physician-reported secondary endpoints. The only adverse event related to Firdapse was mild temporary paresthesia — a feeling of “pins and needles” or numbness on the skin — in 60% of patients.

“Despite the low number of patients, MuSK-001 study provided evidence that amifampridine phosphate (Firdapse), in the range of 30-60mg daily dose, was safe and effective in treating [MuSK-MG],” the scientists stated.

“The results of the pilot study are very encouraging, such that our multi-center pivotal Phase 3 trial evaluating Firdapse for the treatment of MuSK-MG is currently underway,” Gary Ingenito, MD, PhD, and Catalyst’s chief medical officer, said in a press release. “If our Phase 3 trial is successful, we hope that Catalyst will be able to offer physicians and patients alternatives in the treatment of MuSK-MG.”

In MuSK-MG, the body attacks cells that produce a protein called muscle-specific kinase, or MuSK. Together with acetylcholine (ACh), MuSK is required for effective nerve-muscle communication.

Firdapse is an oral, voltage-dependent potassium channel blocker. Firdapse’s 10 mg tablets have been approved for the treatment of adults with Lambert-Eaton Myasthenic Syndrome (LEMS) in the United States and European Union. The therapy is expected to be available for U.S. patients in the first quarter of this year. It is the only approved medication in Europe for the symptomatic treatment of adults with LEMS, a rare autoimmune disease.

Besides MuSK-MG and LEMS, Firdapse is being evaluated in trials of congenital myasthenic syndromes (CMS), and spinal muscular atrophy type 3. It has received orphan drug designation from the U.S. Food and Drug Administration for MuSK-MG and CMS.