Success in rare autoimmune disease trial

Catalyst Pharmaceuticals, Inc. announced positive top-line results from a second Phase III clinical trial (LMS-003) of Firdapse (amifampridine phosphate tablets equivalent to 10 mg amifampridine) for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS). Firdapse received Breakthrough Therapy designation from the FDA in August 2013 and this clinical trial was conducted using a protocol agreed to by the FDA through the Special Protocol Assessment (SPA) process.

This trial had two prospectively defined co-primary endpoints. The first of these, quantitative myasthenia gravis score (QMG), achieved a statistically significant p-value of 0.0004, and the second, subject global impression (SGI), achieved a statistically significant p-value of 0.0003. More importantly, a clinically significant difference of 6.4 points was observed between the Firdapse and placebo groups for the QMG endpoint. Firdapse was well tolerated and showed a similar safety profile to that seen in earlier studies. All p-values reported are based on the entire intent to treat (ITT) population of patients that enrolled in this trial.

The prospectively defined secondary endpoint for the physician's clinical global impression of improvement (CGI-I) achieved statistical significance (p-value 0.0020). Further, the exploratory endpoints had the following results: (i) the triple timed up and go (3TUG) endpoint achieved statistical significance (p-value 0.0112), (ii) the evaluation of the QMG-Limb domains endpoint achieved statistical significance (p-value 0.0010), and (iii) the most bothersome symptom (MBS) endpoint was not statistically significant, but showed a positive trend (p-value 0.0572).

Comment: Firdapse is currently approved in the EU and is the first and only approved drug for the symptomatic treatment of Lambert-Eaton myasthenic syndrome in adults, a rare autoimmune disease with the primary symptoms of muscle weakness.