Catalyst Pharmaceuticals has reported encouraging results from its second phase 3 clinical trial to test the investigational drug amifampridine phosphate (brand name Firdapse) in people with Lambert-Eaton myasthenic syndrome (LEMS). The results support the company’s plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) in the first quarter of 2018.
The completed phase 3 trial was designed to evaluate the effectiveness of amifampridine phosphate in controlling, reducing and/or eliminating symptoms of LEMS. The results indicate the drug — if approved by the FDA — potentially could become an important treatment option for 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.
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, and some forms of myasthenia gravis (MG). It also is under investigation as a treatment for adults and children with congenital myasthenic syndrome.
Earlier in its development, Firdapse received Breakthrough Therapy Designation from the FDA for the treatment of LEMS, and Orphan Drug Designation for LEMS, congenital myasthenic syndromes (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.
A total of 26 people participated in the “withdrawal” trial, which was designed to evaluate the effectiveness of Firdapse in controlling, reducing and/or eliminating LEMS symptoms by enrolling participants who already were taking the drug. Participants were then randomly assigned to groups. In one group, participants continued to receive treatment with Firdapse. In the other group, participants were treated instead with a placebo.
Investigators found that Firdapse was safe and well-tolerated by trial participants.
In addition, those who were treated with Firdapse saw stable or improved scores on several assessment scales and strength tests conducted at different time points throughout the trial, while those who were treated with placebo experienced a worsening of scores and symptoms.
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.