Catalyst Pharmaceuticals Submits New Drug Application to FDA for Firdapse to Treat LEMS

Catalyst Pharmaceuticals has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the investigational drug amifampridine phosphate (brand name Firdapse) for the treatment of people with Lambert-Eaton myasthenic syndrome (LEMS). The FDA has 60 days to determine whether the NDA is complete and acceptable for filing. If the FDA accepts Catalyst’s NDA, it will begin the review to decide whether Firdapse will gain approval in the U.S. for the treatment of people with LEMS.

The NDA follows Catalyst’s announcement in November of encouraging results from its second phase 3 clinical trial to test Firdapse in people with LEMS.

In LEMS the immune system attacks the body’s own tissues

LEMS is an autoimmune disease — a disease in which the immune system attacks the body’s own tissues. The attack occurs at the connection between nerve and muscle (the neuromuscular junction) and interferes with the ability of nerve cells to send signals to muscle cells.

Specifically, the immune system attacks the calcium channels on nerve endings that are required to trigger the release of chemicals (acetylcholine). With fewer calcium channels, the nerve ending releases less acetylcholine, a chemical messenger that triggers muscle contraction. In people with LEMS, the lowered levels of acetylcholine are not sufficient to cause normal muscle contractions, resulting in muscle weakness.

In about 50 to 60 percent of cases, LEMS is associated with an underlying disease, particularly small cell lung cancer. It is thought that the body’s attempt to fight the cancer inadvertently causes it to attack nerve endings because cancer cells share some of the same proteins as nerve endings.

LEMS can affect many muscles, but usually it causes weakness mostly in the upper legs and hips more than the upper arms and shoulders. These proximal muscles are more likely to fatigue with use, and muscle fatigue and sometimes stiffness may be more prominent than actual weakness. The legs are particularly affected and individuals with the disease may have difficulty getting out of a chair, going up stairs, running or walking. Lifting and pushing may be difficult.

Prolonging nerve signals

Firdapse is a potassium channel inhibitor designed to prolong signals released from nerves and allow greater stimulation of muscles. The drug currently is under clinical investigation as a symptomatic therapy to treat LEMS, spinal muscular atrophy (SMA) and some forms of myasthenia gravis (MG). It also is under investigation as a treatment for adults and children with congenital myasthenic syndrome (CMS).

Earlier in its development, Firdapse received Breakthrough Therapy Designation from the FDA for the treatment of LEMS, and Orphan Drug Designation for LEMS, CMS and MG. It is approved in Europe to treat LEMS in adults.

MDA has supported previous studies of amifampridine phosphate in children with CMS.

Expanded Access Program

Catalyst Pharmaceuticals has an Expanded Access Program (EAP) for Firdapse for people with LEMS or some types of CMS. The program is an open label pre-approval safety study in which people who meet the inclusion and exclusion criteria can receive Firdapse, at no cost, when their physician determines it may help improve the person’s condition.

For questions about the EAP, call 844-347-3277, and be sure to check back at mda.org for updates.