Catalyst Pharmaceuticals announced that it will soon begin a Phase 3 clinical trial to assess Firdapse (amifampridine phosphate) in people with myasthenia gravis who are positive for the MuSK antibody.
In meetings, the company and the U.S. Food and Drug Administration (FDA) arrived at an agreement regarding the size, scope and objectives of the trial, which is expected to start recruiting patients early in 2018. The study will evaluate Firdapse’s safety and efficacy in people with MuSK antibody positive myasthenia gravis (MuSK-MG), a particularly severe form of the disease.
It will be conducted at multiple centers within the U.S. and in Italy, and aims to enroll 60 patients diagnosed with MuSK-MG.
Researchers will measure Myasthenia Gravis Activities of Daily Living (MG-ADL) as the trial’s primary endpoint, and assess participants’ changes in the Quantitative Myasthenia Gravis Score as a secondary measure of effectiveness. The study will also recruit 10 generalized myasthenia gravis patients, an FDA request. All patients will evaluated under these outcomes.
“We are pleased to report that we have reached an agreement with the FDA under a Special Protocol Assessment (SPA) for the trial design, clinical endpoints and statistical analysis approach for our Phase 3 clinical trial evaluating Firdapse for the treatment of patients with MuSK antibody positive Myasthenia Gravis,” Patrick J. McEnany, CEO of Catalyst, said in a press release. “We appreciate the FDA’s engagement and guidance during the SPA process.”
Two studies testing Firdapse, a neuronal potassium channel blocker that works to improve nerve impulses to muscle, are now underway in people with myasthenia gravis. The LEMS study (NCT02970162) is recruiting patients with Lambert-Eaton Myasthenic Syndrome (LEMS), and Catalyst expects this trial to soon be fully enrolled. Depending on its results, Catalyst is considering filing a new drug application requesting that the FDA approval Firdapse as a LEMS treatment in early 2018.
Before submitting an NDA, the FDA requested Catalyst to undergo a series of preclinical abuse liability tests, to ensure that Firdapse does not exhibit any abuse liability concerns. The company is conducting three such studies, two of which are completed and confirmed the drug’s safety. A third “drug discrimination” study is ongoing and expected to finish by year’s end.
Dr. Steven Miller, Catalyst’s chief operating and chief scientific officer, said, “The additional short term preclinical studies that the FDA required us to complete before we could submit another NDA for amifampridine phosphate are abuse liability studies … for the evaluation of the potential effect of any new chemical entities on behaviors relating to abuse liability and dependence/withdrawal effects. … [W]e now expect to have the final report in December.”
A second trial (NCT02562066) for patients with congenital myasthenic syndromes (CMS) is also recruiting participants. Top-line results from this trial are due to be released by mid-2018.