Catalyst Pharmaceuticals recently enrolled the first patient into a Phase 3 clinical trial designed to evaluate the efficacy and safety of Firdapse (amifampridine phosphate) in patients with MuSK antibody-positive myasthenia gravis (MuSK MG).
Firdapse is a neuronal potassium channel blocker that works to improve nerve impulses to muscle.
In MG, the body attacks special receptors on nerve cells that are sensitive to an important chemical called acetylcholine (ACh). This chemical is responsible for the communication across the neuromuscular junction to muscles, where acetylcholine receptors (AChR) interpret the message and cause muscles to contract.
A second chemical that is needed for healthy nerve-muscle communication is called muscle-specific kinase, or MuSK. Unlike AChR-MG, where the body attacks the receptor, in patients with MuSK-MG, their bodies attack cells that produce the MuSK chemical.
MuSK MG is a particularly severe form of myasthenia gravis and is estimated to affect between 3,000 and 4,800 people in the United States.
The MSK-002 trial (NCT03304054) is now recruiting up to 60 people diagnosed with MuSK MG in the U.S. and Italy. The study’s primary endpoint is the measurement of Myasthenia Gravis Activities of Daily Living (MG-ADL). The secondary endpoint is to measure Quantitative Myasthenia Gravis Score (QMG).
“By conducting this Phase 3 study in patients with MuSK-MG, we hope to provide a potential treatment option for people suffering from this rare condition,” Patrick J. McEnany, chairman and CEO of Catalyst, said in a press release.
“Catalyst continues to build a leadership position in developing therapies to treat rare neuromuscular diseases with this next step for an important investigational product to potentially treat the symptoms of MuSK-MG,” he said.
Catalyst reached an agreement last August with the U.S. Food and Drug Administration regarding a special protocol assessment (SPA) for the design, clinical endpoints, and statistical approach for the Phase 3 trial. The pharmaceutical company agreed to the FDA’s request to also enroll up to 10 generalized MG patients.
These patients will be assessed with the same clinical endpoints, but achieving statistical significance in this subgroup of patients is not required. Enrollment should be completed in 12 months.
“There is a significant unmet medical need to treat the symptoms of MuSK-MG, and these patients are eagerly awaiting a new treatment option,” said Gary Ingenito, an MD and PhD, and chief medical officer at Catalyst. “The previous Catalyst supported, proof-of-concept investigator-sponsored study in MuSK-MG patients showed impressive clinical improvement in multiple measures.
“We’re pleased to have begun enrolling patients in this study and look forward to working closely with the MG community to advance Firdapse through this Phase 3 trial,” he added.
Firdapse was granted FDA orphan drug status for the treatment of MG and Lambert-Eaton Myasthenic Syndrome (LEMS).
Firdapse in oral tablet form is approved in the European Union to treat LEMS.
Two other studies testing Firdapse are now underway in people with MG. The first (NCT02970162), now completed, was a Phase 3 trial designed to evaluate the effect of withdrawing Firdapse from patients with LEMS in a 50/50 ratio.
A second trial (NCT02562066), now recruiting patients with congenital myasthenic syndromes (CMS), is evaluating the efficacy and safety of Firdapse in patients diagnosed with certain types of CMS.
Catalyst has filed a new drug application (NDA) requesting FDA approval of Firdapse as a LEMS treatment. The NDA could open a regulatory pathway for additional approvals in MG and MuSK MG.