Catalyst Pharma's Firdapse bet on congenital myasthenic syndromes turns sour
Months after Firdapse maker Catalyst Pharmaceuticals filed a lawsuit against the FDA, the Florida company on Wednesday said the drug had failed a pivotal trial in patients afflicted with congenital myasthenic syndromes (CMS), an umbrella term for rare neuromuscular disorders comprising a spectrum of more than 50 genetic defects.
The drug, known chemically as amifampridine, was sanctioned for use in adult Lambert-Eaton myasthenic syndrome (LEMS) patients in November 2018. The company is working on expanding the label to include patients with CMS, MuSK-positive myasthenia gravis (MuSK-MG) and spinal muscular atrophy (SMA).
Catalyst estimates that there are between 1,000 and 1,500 CMS patients in the United States — there are at least 600 families with affected individuals who have been represented in scientific literature, according to the NIH. Patients with CMS carry mutations in genes encoding proteins essential for neuromuscular transmission.
Catalyst’s late-stage study tested the drug against a placebo in genetically confirmed CMS patients. 20 patients aged two and above were enrolled in the trial, and 16 were randomized. The drug failed to meet the main goal of subject global impression (SGI) scale, a measure used by clinicians to rate the severity of the illness at the time of assessment, relative to the clinician’s past experience with patients with the same diagnosis.
The company’s shares $CPRX slipped about 12.3% to $5 in premarket trading.
The secondary endpoint of muscle function measure (MFM) across all tested subtypes was also not met, although individual patient improvements were observed in some patient sub-groups, the company said.
“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,” Steven Miller, Catalyst’s COO and CSO said in a statement.
The company will meet the FDA before the end of 2019 to figure out the next steps for the CMA program. Meanwhile, the Catalyst expects to report data from the MuSK-MG trial as well as results from its SMA proof of concept study in the first half of next year.
Having launched in January, Firdapse generated about $41.3 million in sales in the first half of this year. Before the drug (which carries an average annual list price of $375,000) was approved by the FDA, hundreds of patients had been able to access a similar drug from compounding pharmacies for a fraction of the cost, or Jacobus’ for free, as part of an FDA-ratified compassionate use program.
But the approval of the Catalyst drug — accompanied by market exclusivity spanning seven years — effectively precluded Jacobus and compounding pharmacies from selling their versions.
Then, in an unexpected twist, the FDA endorsed New Jersey-based Jacobus’ version in pediatric patients, on the basis of adult data — a move that could spark off-label prescription in adults (As far as the FDA is concerned, doctors can prescribe drugs for off-label use when they judge that it is medically appropriate for their patient). Adding fuel to the fire, Jacobus’s drug, Ruzurgi, carries a list price that is less than half of Firdapse’s. Catalyst maintains that typically, covered patients pay less than $10 per month out-of-pocket.
In an interview with Endpoints News ahead of Catalyst’s third-quarter results expected mid-November, chief Patrick McEnany said that the Ruzurgi approval has triggered a “trickle of erosion” on its LEMS patient base. “It was not unexpected,” he said.
In June, Catalyst filed a lawsuit against the health regulator — effectively accusing the agency of bowing to political pressure surrounding skyrocketing drug prices. Under federal law, the agency is meant to treat all companies in the same manner. Catalyst has asserted the agency undermined its orphan drug exclusivity, and violated federal law by playing favorites in the context of a hypervigilant pricing environment.