CMS is so Rare That it Took Four Years to Enroll Twenty People for a Trial


According to a recent article in Biospace, Catalyst Pharmaceutical’s CMS-001 Phase 3 study ended with mixed results. The trial was billed as the first placebocontrolled double-blind study testing amifampridine phosphate (brand name Firdapse).

The drug is designed to treat congenital myasthenic syndromes (CMS) in adults or children over the age of two who have specific CMS subtypes. Firdapse was approved by the FDA in November 2018 for Lambert-Eaton myasthenic syndrome in adults.

About the CMS-001 Trial

Out of twenty people who were selected for the randomized control trial, sixteen were assigned to one of two groups. Subjects in the first group were treated with amifampridine phosphate, the drug that is being evaluated.

It is noteworthy that CMS is so rare that it took about four years to complete a minimum enrollment of twenty people.

The second group was treated with an alternative therapy for comparison (the control group).

One of the reasons to assign patients to a group randomly is to avoid skewing or manipulating the results (bias). In other words, unless patients are assigned randomly, scientists and the patients themselves may influence the results.

Results from the CMS-001 Trial

The study did not meet its primary endpoint. Clinicians were required to assess whether the patients’ illness had improved or worsened using a point system.

The secondary endpoint also failed. It is the measure of muscle function across all subtypes that had been tested. Catalyst and the FDA will be reviewing the data later this year.

The three main CMS subtypes are identified by the way in which they affect connections between the nervous system and muscle.

About Congenital Myasthenic Syndromes (CMS)

CMS is a neuromuscular disorder. Although more than fifty genetic defects are associated with CMS, only a few patients have been located and diagnosed with specific CMS mutations.

CMS symptoms include weak skeletal muscles. These symptoms appear a short time after birth or in early childhood.

There are approximately fifteen hundred CMS patients in the United States. The number of CMS patients is estimated to be about one-tenth of the number of myasthenia gravis patients.

About Amifampridine Phosphate (Firdapse®)

Firdapse® is being analyzed not only for CMS but for other neurological and neuromuscular diseases in anticipation of future applications to the FDA.

For instance, the FDA granted Breakthrough Therapy Designation to Firdapse® for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) an autoimmune disorder. FDA Breakthrough Therapy designation helps to expedite drug development and review. Further, Firdapse is the only drug that is approved in Europe for LEM patients.

In addition, Orphan Drug Designation was awarded to Firdapse® by the FDA for treatment of LEMS, CMS and myasthenia gravis. Orphan Drug Designation provides financial incentives to companies for the development of biologics and drugs for rare diseases.

For example, Firdapse is being evaluated in a Phase 3 trial for MSK-002 involving patients with anti-MuSK antibody-positive myasthenia gravis (MuSK-MG). Enrollment is scheduled for completion by year-end Results will be available in early 2020.

Catalyst also anticipates reporting results from their spinal muscular atrophy (SMA) Type-3 study in early 2020. Firdapse improves signaling between the muscle and nerve at the point where the muscle connects to the motor neuron.

According to the company, both SMA and MuSK-MG are somewhat similar in nature and therefore may not present the challenges that were encountered in the CMS Phase 3 trial.

About Catalyst Pharmaceuticals 

Catalyst Pharmaceuticals, a biopharmaceutical company, develops therapies for the treatment of rare chronic neurological and neuromuscular diseases.

 The CEO of Catalyst acknowledged their disappointment at the poor results of primary and secondary endpoints. However, he emphasized that the discovery of valuable information will benefit patients and the medical community in the long run.

He also reminded the community that Catalyst is still committed to continuing its work in developing FDA approved drugs to treat rare neuromuscular diseases.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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