Firdapse Falls Short in Phase 3 Trial in MuSK-MG Patients, Top-line Results Show

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Firdapse trial results

Firdapse (amifampridine phosphate), an investigational treatment for MuSK-antibody positive myasthenia gravis (MuSK-MG), failed to meet its primary or secondary goals, according to top-line results from a Phase 3 clinical trial. 

The randomized trial (NCT03304054), dubbed MSK-002 and sponsored by the therapy’s developer, Catalyst Pharmaceuticals, involved 70 adults with MuSK-MG who received either 10 mg tablets of Firdapse, increased to an effective and tolerable dose, or a placebo three to four times daily for 10 days. 

According to the results, it did not achieve statistical significance in either its primary objective, the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment, or secondary measure, the Quantitative Myasthenia Gravis (QMG) assessment, in treated patients compared with those who received the placebo. 

Catalyst says it will complete a full analysis of the data and meet with neuromuscular advisers to plan a path forward for the treatment of MuSK-MG. Full details of the study are expected to be released in a future scientific meeting. 

The Phase 3 trial was supported by a previous proof-of-concept Phase 2b trial (2015-003127-62), called MuSK-001, in 10 MuSK-MG patients, which showed statistically significant changes in both MG-ADL and QMG scores after Firdapse treatment.

“We are disappointed that the top-line results of our Phase 3 study for Firdapse anti-MuSK antibody positive myasthenia gravis patients did not replicate the robust positive results that were observed in the 2017 proof-of-concept study,” said Patrick J. McEnany, CEO of Catalyst, in a press release

“We intend to continue to analyze the data and meet with our neuromuscular key opinion leaders to decide on our path forward for this program,” he said.

In MuSK-MG, autoantibodies mistakenly attack cells that produce a protein called muscle-specific kinase, or MuSK. Together with the neurotransmitter acetylcholine, MuSK is necessary for nerve-muscle communication.

Firdapse is an oral, voltage-dependent potassium channel blocker that increases acetylcholine levels at the neuromuscular junction, the connection between nerve and muscle cells. 

Firdapse is approved for the treatment of the rare autoimmune disorder Lambert-Eaton myasthenic syndrome (LEMS) in the U.S., the European Union, and elsewhere. It also was approved recently in Canada. Clinical trials showed that Firdapse significantly eased muscle weakness in LEMS patients.

Firdapse was found to be safe and well-tolerated during the MSK-002 study, similar to that seen in the treatment of LEMS. The most common side effects reported were the sensation of pins and needles, as well as gastrointestinal problems such as nausea, stomach pain, and diarrhea.

Catalyst also is investigating the impact of Firdapse in people with the inherited neurodegenerative disease spinal muscular atrophy, which is characterized by progressive muscle weakness.