One last study in LEMS

CORAL GABLES, Fla.—Weeks after announcing positive results from a Phase 3 study of its drug candidate Firdapse, Catalyst Pharmaceuticals is preparing for yet another study of the drug. The follow-up research is a somewhat unexpected hurdle that emerged as a result of the U.S. Food and Drug Administration’s (FDA) insistence that Catalyst submit additional positive results from another adequate and well-controlled study in patients with Lambert-Eaton myasthenic syndrome (LEMS), a rare, frequently disabling autoimmune neuromuscular disorder that produces serious muscle weakness and symptoms of autonomic dysfunction.

The initial Phase 3 study was a multicenter, randomized, double-blind, placebo-controlled withdrawal trial. All 38 patients enrolled in the study were initially treated with Firdapse followed by treatment with either Firdapse or placebo during a two-week randomization period. The trial was designed so that the clinically significant findings, when present, consisted of worsening symptoms in the placebo group.

“Our goal with this study was to demonstrate that the drug was safe and effective and with these results we achieved that goal,” Pat McEnany, CEO of Catalyst, tells DDNews. “We were operating under the assumption that what we needed for approval was one adequate and well-controlled study, in addition to providing well-supported literature.”

The study’s results were published in the May 2016 issue of Muscle & Nerve. But when Catalyst representatives met with the FDA earlier in the spring, it became clear that the company would need to provide additional data.

“The FDA offered suggestions in our meeting for how we could make an efficient, small and short-term study, and we have heard back from them a few weeks ago confirming their approval of the study protocols” says McEnany. “We are still fine-tuning the endpoints and logistics, but it will be a single-site, short-term study and we will be making public more details in about six to eight weeks.”

The Phase 3 study protocol agreed upon by the FDA and Catalyst is expected to move forward during the second half of 2016. “We are pleased to have the FDA’s agreement on the design of the protocol for our second Phase 3 trial evaluating Firdapse for the treatment of LEMS,” McEnany remarked in a public statement. “This is an important milestone in our effort to provide all LEMS patients with access to an FDA approved therapy.”

McEnany also says that Catalyst’s latest analysis of its financials show that the company is prepared to fund the next study. “Additionally, we have recently completed an analysis of our cash forecasts and budgets under our reorganized operational plan and believe, based on currently available information, that our existing capital resources are adequate to get us to an accepted NDA submission without the need for additional financing.”

Firdapse is the lead drug candidate of Catalyst, which acquired North American rights to the compound in 2012 from BioMarin. Firdapse has since received both Breakthrough Therapy Designation and Orphan Drug Designation from the FDA for the treatment of LEMS.

LEMS is a rare autoimmune disease that is estimated to affect between 320 to 3,000 patients in the United States. About 50 percent of patients with LEMS, particularly male smokers, present with an underlying malignancy, usually small cell lung cancer.

“Publication in Muscle & Nerve, a leading medical publication devoted to neuromuscular disorders and treatments, further validates the strength of the Phase 3 data that showed a significant benefit for patients taking Firdapse,” Gary Ingenito, chief medical officer of Catalyst, said in a public statement.

Catalyst is also continuing the development of Firdapse for additional indications. It has initiated an investigator-sponsored study of Firdapse in patients with MuSK-antibody positive myasthenia gravis, and this year the company also expects to complete a clinical trial of Firdapse for pediatric patients with congenital myasthenic syndromes.