Rare Daily Staff

Catalyst Pharmaceuticals released positive top-line results from a second late-stage clinical trial of Firdapse for the symptomatic treatment of Lambert-Eaton myasthenic syndrome or LEMS, a rare autoimmune disorder, most often characterized by muscle weakness of the limbs.

The company plans in the first quarter of 2018 to file an application with the U.S. Food and Drug Administration to market the drug in the United States.

Patients with LEMS develop antibodies against voltage gated potassium channels in the connection between nerves and the muscles they communicate with. In about half of the cases, LEMS is associated with an underlying malignancy, most commonly small-cell lung cancer, and in some individuals, LEMS is the first symptom of such malignancy. LEMS generally affects the extremities, especially the legs. As the disease most affects the parts of limbs closest to the trunk, difficulties with climbing stairs or rising from a sitting position are commonly noted. Individuals affected with LEMS also may have a disruption of the autonomic nervous system, including dry mouth, constipation, blurred vision, impaired sweating, and/or hypotension.

Firdapse won European approval at the end of 2009 and has been available in Europe since April 2010. Catalyst, which licensed the drug in the United States from BioMarin, first sought U.S. approval in 2014, but the FDA said it would not approve the drug without an additional clinical trial. The FDA granted Firdapse Breakthrough Therapy designation in August 2013.

Catalysts conducted its most recent Firdapse trial using a protocol agreed to by the FDA through the Special Protocol Assessment process. The Special Protocol Assessment process is intended to provide greater certainty to drug developers by allowing them to reach agreement with the agency over the design of a late-stage study prior to beginning it.

The study found Firdapse met statistical significance on its primary and secondary endpoints. It also showed Firdapse was well tolerated and showed a similar safety profile to that seen in earlier studies. The majority of adverse events in each category occurred in the group assigned to placebo as they experienced a return of their LEMS symptoms. There were no serious adverse events during the trial.

This clinical trial was designed as a double blind, randomized, withdrawal trial in which LEMS patients who were currently receiving Firdapse in Catalyst’s Expanded Access Program were invited to participate in study. Upon completion of screening, patients were treated with either Firdapse or placebo (randomly assigned, 1:1). A total of 26 patients completed the randomized treatment. In a trial of this design, the clinically significant findings, when present, are worsening of symptoms in the placebo group. All endpoints were evaluated as a change from baseline.

Although the protocol allowed for subjects to be rescued if the treatment during the randomization phase resulted in an intolerable level of symptoms or effect on ambulation, no subjects required rescue and all 26 subjects completed the randomization phase to provide pre- and post-treatment assessment data. All patients who participated in the trial are continuing to participate in Catalyst’s EAP following completion of the trial.

The two co-primary endpoints were quantitative myasthenia gravis score, or QMG score, and subject global impression or SGI. The QMG score is a physician-rated semi-quantitative evaluation consisting of 13 assessments (each rated 0 to 3), which are totaled to obtain a QMG score, and includes tests for arm strength, leg strength, face and neck muscle performance, swallowing, speech, grip strength, forced respiration, and gaze impairment. The SGI score is a subjective scale on which the patients rate their satisfaction with the effects of Firdapse or placebo on their LEMS symptoms with scores from 1 (“Terrible”) to 7 (“Delighted”).

“We are extremely pleased with the top-line efficacy and safety results from this second Phase 3 trial, which reinforces the potential of Firdapse to be an important treatment for patients suffering from LEMS,” said Patrick McEnany, president and CEO of Catalyst Pharmaceuticals. “We look forward to presenting further data in future publications and at medical conferences,” “Catalyst remains committed to the development of therapies that will improve the function and lives of people with rare neurodegenerative diseases.”

November 27, 2017

Photo: Patrick McEnany, president and CEO of Catalyst Pharmaceuticals