FDA Approves Arimoclomol, First Drug for Niemann-Pick Disease, Type C

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has granted approval to Zevra Therapeutics’ arimoclomol (Miplyffa), an oral medication designated for the treatment of Neimann-Pick disease, type C (NPC).¹

Announced by the agency on September 20, 2024, arimoclomol, in combination with miglustat, was approved to treat neurological symptoms linked to NPC in adults and children aged ≥2 years, marking the first drug to get the green light to treat NPC.

“NPC is a serious disease that leads to enormous adverse impacts on patients and families. Despite extensive research efforts, there have not been approved treatments to meet the significant needs of patients,” said Janet Maynard, MD, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine (ORPURM), in the FDA Center for Drug Evaluation and Research. “The first-ever approval of a safe and effective drug option for NPC will undoubtedly support the essential medical needs of those suffering.”

A rare genetic disease, NPC can result in progressive neurological symptoms and organ dysfunction.² It originates from changes in the NPC1 or NPC2 genes, impacting the transport of cholesterol and other lipids in a cell, ultimately leading to organ damage. Evidence has shown patients affected by NPC only live for an average of 13 years.

Arimoclomol’s safety and effectiveness were assessed in a randomized, double-blind, placebo-controlled 12-month trial.¹ A total of 50 patients aged 2–19 years, with a molecularly confirmed diagnosis of NPC, were randomized 2:1 to weight-adjusted arimoclomol (31–124 mg) or oral placebo three times per day.

Of the trial population, 39 (78%) received miglustat as background treatment. Efficacy was measured by the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score, a measure of NPC disease progression, including ambulation, speech, swallow, and fine motor skills. Higher scores on the R4DNPCCSS indicate greater severity of NPC.

Upon analysis, the R4DNPCCSS demonstrated the efficacy of arimoclomol in patients who received miglustat as background therapy. Arimoclomol achieved slower disease progression, as measured by the 4 domains, compared with placebo therapy.

Arimoclomol, in combination with miglustat, was indicated for oral treatment with or without food, according to the recommended dose based on a patient’s body weight. The drug’s prescription information warned of hypersensitivity reactions, including hives and angioedema, advising individuals who experience these reactions to halt use.

Female patients who are pregnant or plan to become pregnant were advised not to use arimoclomol. Based on safety data, the most common side effects linked to arimoclomol included upper respiratory tract infection, diarrhea, and decreased weight.

The agency previously granted arimoclomol Priority Review, Orphan Drug, Rare Pediatric Disease, Fast Track, and Breakthrough Therapy designations for the treatment of NPC. In August, arimoclomol was the first product application discussed at the Genetic Metabolic Diseases Advisory Committee (GeMDAC), a committee established to advise the FDA on products used for the prevention or treatment of genetic metabolic diseases.

References

1. _{Commissioner O of the. FDA approves first treatment for Niemann-Pick disease, type C. U.S. Food and Drug Administration. September 20, 2024. Accessed September 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-niemann-pick-disease-type-c.}
2. _{Bianconi SE, Hammond DI, Farhat NY, et al. Evaluation of age of death in Niemann-Pick disease, type C: Utility of disease support group websites to understand natural history. Mol Genet Metab. 2019;126(4):466-469. doi:10.1016/j.ymgme.2019.02.004}