FDA Accepts Catalyst’s NDA for Firdapse with Priority Review Status for LEMS

The U.S. Food and Drug Administration has accepted Catalyst Pharmaceuticals’ new drug application (NDA) for Firdapse (amifampridine phosphate) for Lambert-Eaton myasthenic syndrome (LEMS), with priority review status.

Firdapse is a formulation of amifampridine phosphate in development for the treatment of LEMS as well as other conditions. Several clinical studies have helped support Firdapse’s efficacy profile, including one double-blind trial with an active comparator in patients with LEMS.

The primary symptom of LEMS is muscle weakness caused by a reduction in the amount of the neurotransmitter acetylcholine (ACh) released from nerve terminals.

Firdapse is a neuronal potassium channel blocker that leads to the opening of slow voltage-dependent calcium channels, allowing for an influx of calcium. The drug also induces the secretion of synaptic vesicles to release more ACh into the synaptic space, enhancing neuromuscular transmission and improving muscle function.

Firdapse has been studied for the treatment of LEMS in two Phase 3 trials.

The first trial was the Phase 3 LMS-002 clinical trial (NCT01377922), a multi-center, double-blind, placebo-controlled, randomized discontinuation study, designed in four parts to evaluate the effectiveness and safety of multiple doses of Firdapse in patients with LEMS.

The second was the Phase 3 LMS-003 clinical trial (NCT02970162), a double-blind, placebo-controlled, randomized, parallel-group study designed to evaluate the effectiveness and safety of Firdapse in patients with LEMS.

Data from these studies demonstrated statistically significant improvements across a number of independent measures of neurological function, including Quantitative Myasthenia Gravis (QMG) score and compound muscle action potential (CMAP), which have been shown to be clinically relevant in patients with LEMS.

Firdapse has received FDA breakthrough therapy designation for the treatment of LEMS, as well as orphan drug status for LEMS, myasthenia gravis (MG), and congenital myasthenic syndromes (CMS).

In Europe, Firdapse is the first and only drug approved for symptomatic treatment in adults with LEMS.

Priority review status is granted in the U.S. to drugs with the potential to address a serious condition. If approved, the drug should lead to significant improvements in safety or effectiveness of the treatment, or improvements in prevention or diagnosis of the condition.

For Firdapse, the FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Nov. 28, 2018. The submission is supported by positive results obtained in the LMS-002 and LMS-003 studies.

“We are delighted to have received Priority Review status for Firdapse for the treatment of LEMS and look forward to continuing to work closely with the FDA during the review process,” Patrick J. McEnany, chairman and CEO of Catalyst, said in a press release.

“Together with the previous grant of Breakthrough Therapy Designation, the Priority Review underscores the robust potential of Firdapse and the need for a safe and effective FDA-approved treatment for LEMS,” he said.

Firdapse has been made available since 2014 on a compassionate use basis through an Expanded Access Program while the company seeks FDA approval.