Rare Daily Staff

Catalyst Pharmaceuticals reported that its drug Firdapse failed a late-stage trial evaluating it for the symptomatic treatment of adults and children aged 2 years and older with genetically confirmed Congenital Myasthenic Syndromes.

Congenital myasthenic syndromes, or CMS, are rare neuromuscular disorders comprising a spectrum of more than 50 genetic defects with some of the various mutations having as few as a handful of diagnosed patients. CMS patients are characterized by fatigable weakness of skeletal muscles with onset at or shortly after birth or early childhood; in rare cases, symptoms may not manifest themselves until later in childhood. The severity and course of the genetic disease types are variable, ranging from minor symptoms to progressive disabling weakness; symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency also occur. Catalyst estimates that there are between 1,000 and 1,500 CMS patients in the United States.

The trial of 20 patients did not meet its primary endpoint of subject global impression or the secondary endpoint of muscle function measure across all tested subtypes. Due to the rarity of CMS, the trial took almost four years to recruit.

“While we are disappointed that this trial did not reach its primary or secondary endpoints in the evaluated CMS patient subtypes, we are pleased with the new valuable clinical information that these results will provide to the medical and scientific communities as we work to develop FDA-approved treatment options for patients with this disease,” said Patrick McEnany, chairman and CEO of Catalyst.

Catalyst is scheduled to meet with the U.S. regulatory agency before the end of the year to discuss the outcome of this clinical trial, and potential paths forward to seek approval of Firdapse for the symptomatic treatment of some subset of genetic subtypes of CMS. 

Firdapse is approved to treat adults with Lambert-Eaton Syndrome, or LEMS, a rare disorder of the neuromuscular junction. The company raised a lot of controversy over the price of its LEMS treatment, which had been available for free for many years from Jacobus Pharmaceuticals under a compassionate use program. It went so far as to sue the U.S. Food and Drug Administration after the agency approved the use of Jacobus’ Rizurgi for the treatment of LEMS in children.

Firdapse is also being studied in trials as a treatment for patients with anti-MuSK antibody positive myasthenia gravis (MuSK-MG), and spinal muscular dystrophy type 3. The company says both of these diseases have a much more homogeneous patient population than CMS and should not present the same challenges.

“We have made significant progress in genetically testing patients who were unable to previously get diagnosed,” added Steven Miller, chief operating office and chief scientific officer of Catalyst Pharmaceuticals.  “Due to the small patient prevalence, the low number of patients tested, and heterogeneity of the disease with a wide range of variation in clinical presentation across its more than 50 subtypes, it was challenging to demonstrate a statistically significant benefit across multiple subtypes.”

Photo: Patrick McEnany, chairman and CEO of Catalyst

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