FDA Approves Dose Expansion of Catalyst's Amifampridine for Lambert-Eaton Myasthenic Syndrome

Richard J. Daly, MBA

(Credit: LinkedIn)

The FDA has approved a supplemental new drug application (sNDA) for a higher maximum daily dose of Catalyst Pharmaceuticals’ potassium channel blocker amifampridine (Firdapse) for the treatment of adults and pediatric patients with Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder characterized primarily by muscle weakness of the limbs.¹ The decision expands the dosage options to include daily dosing of 80 mg to 100 mg for patients with the disease weighing more than 45 kg.

“We are pleased to receive the approval for the increased maximum daily dose of Firdapse,” Richard J. Daly, MBA, president and CEO of Catalyst, said in a statement.¹ “This pivotal achievement further underscores our dedication to meeting the evolving needs of LEMS patients and their healthcare providers. We believe that this milestone will have a meaningful impact on the lives of LEMS patients, offering a new level of flexibility in treatment while aligning with our overarching mission to optimize LEMS patient outcomes.”

In November 2018, the FDA approved the drug for patients with LEMS aged 17 and older and approved the expanded use of the treatment to include patients as young as age 6 in 2022. The treatment approval for adults was based on findings from a pair of phase 3 trials, LMS-002 (NCT01377922) and LMS-003 (NCT02970162) which demonstrated the efficacy of amifampridine, clinically relevant differences over placebo in Quantitative Myasthenia Gravis (QMG) score.²

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The first trial, LMS-002, was a double-blind, placebo-controlled, randomized, parallel-group study aimed to assess the efficacy and safety of amifampridine in patients with LEMS. The trial enrolled 38 adults with LEMS who received a maximum single dose of 20 mg of amifampridine or placebo 3 to 4 times per day for a total daily dose of 30-80 mg, for 2 weeks.

The second trial, LMS-003, was a multicenter, double-blind, placebo-controlled study, conducted in 4 parts to investigate the efficacy and safety of multiple doses of amifampridine in patients with LEMS. The trial enrolled 26 adults with LEMS who were randomly assigned to a 4-day oral treatment with either 10 mg of amifampridine or placebo 3 to 4 times per day for a daily total dose of 30-80 mg.

The expanded approval of amifampridine to include patients aged 6 to 17 years old with LEMS followed a few months after the FDA had invalidated its approval of Ruzurgi (Jacobus Pharmaceutical), a therapy previously approved for pediatric patients with LEMS in the United States. Ruzurgi had the same active ingredient as Catalyst's drug, amifampridine, which enhances muscle strength by improving the power of the chemical signals sent from nerve cells to muscles thus, instructing them to contract.³

After Ruzurgi's approval in 2019, Catalyst sued the FDA, alleging the agency’s decision to grant the approval of a treatment that contained the same active ingredient infringed on the marketing exclusivity rights the FDA had given Catalyst when their drug was still an experimental medication and received orphan drug designation. A federal appeals court sided with Catalyst, which led the FDA to invalidate Jacobus Pharmaceutical's Ruzurgi approval. Catalyst then acquired the rights to Ruzurgi in a settlement, ending a 3-year legal battle with Jacobus Pharmaceutical.

LEMS is caused by an autoimmune reaction where antibodies are formed against voltage-gated calcium channels on nerve endings which can damage the channels. The channels typically transport charged calcium atoms that activate the biochemical machinery to release acetylcholine, the neurotransmitter that causes muscles to contract, and failure to release enough of this neurotransmitter can lead to muscle weakness in patients with LEMS.

REFERENCES
1. Catalyst Pharmaceuticals Receives U.S. FDA Approval For Increased Maximum Daily Dose For FIRDAPSE®. News Release. Catalyst Pharmaceuticals. Published May 30, 2024. Accessed June 3, 2024. https://ir.catalystpharma.com/news-releases/news-release-details/catalyst-pharmaceuticals-receives-us-fda-approval-increased
2. FDA approves first treatment for Lambert-Eaton myasthenic syndrome, a rare autoimmune disorder. News Release. FDA. Published November 28, 2018. Accessed June 3, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-lambert-eaton-myasthenic-syndrome-rare-autoimmune-disorder
3. Catalyst Pharmaceuticals Announces Settlement of U.S. Patent Litigation and Resolution of Litigation Challenging Ruzurgi® Approval with Jacobus Pharmaceutical. News Release. Catalyst Pharmaceuticals. Published July 12, 2022. Accessed June 3, 2024. https://ir.catalystpharma.com/news-releases/news-release-details/catalyst-pharmaceuticals-announces-settlement-us-patent