FDA approves arimoclomol, the first drug for Niemann-Pick disease type C

The U.S. Food and Drug Administration (FDA) has approved Zevra Therapeutics’ arimoclomol (Miplyffa), an oral medication for the treatment of Neimann-Pick disease type C (NPC).¹

As the agency announced on September 20, 2024, arimoclomol in combination with miglustat has been approved to treat neurological symptoms associated with NPC in adults and children aged 2 years and older, making it the first drug to receive the green light to treat NPC.

“NPC is a serious disease that has a tremendous negative impact on patients and families. Despite extensive research efforts, there are no approved treatments that address the significant needs of patients,” said Janet Maynard, M.D., director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine (ORPURM) in the FDA's Center for Drug Evaluation and Research. “The first-ever approval of a safe and effective drug option for NPC will undoubtedly address the essential medical needs of those affected.”

NPC is a rare genetic disorder that can lead to progressive neurological symptoms and organ dysfunction.² It is caused by changes in the NPC1 or NPC2 genes that affect the transport of cholesterol and other lipids in a cell, ultimately leading to organ damage. There is evidence that patients with NPC survive an average of only 13 years.

The safety and efficacy of arimoclomol were evaluated in a randomized, double-blind, placebo-controlled 12-month study.¹ A total of 50 patients aged 2–19 years with a molecularly confirmed diagnosis of NPC were randomized 2:1 to receive weight-adjusted arimoclomol (31–124 mg) or oral placebo three times daily.

Thirty-nine (78%) of the trial participants received miglustat as baseline treatment. Efficacy was measured using the re-evaluated 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score, a measure of disease progression in NPC that includes walking, speaking, swallowing, and fine motor skills. Higher scores on the R4DNPCCSS indicate more severe NPC.

When analyzed, the R4DNPCCSS demonstrated the efficacy of arimoclomol in patients receiving miglustat as background therapy. Arimoclomol achieved slower disease progression compared to placebo therapy, as measured by the 4 domains.

Arimoclomol was intended for oral treatment in combination with miglustat with or without food, depending on the recommended dose based on the patient's body weight. The drug's prescribing information warned of hypersensitivity reactions, including hives and angioedema, and advised people who experienced these reactions to stop taking it.

Patients who are pregnant or planning to become pregnant were advised not to take arimoclomol. Based on safety data, the most common side effects of arimoclomol were upper respiratory tract infection, diarrhea, and weight loss.

The agency had 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 in the Genetic Metabolic Diseases Advisory Committee (GeMDAC), a committee that advises the FDA on products intended to prevent or treat genetic metabolic diseases.

References

1. _{FDA Commissioner O Approves First Treatment for Niemann-Pick Disease, Type CUS Food and Drug Administration. September 20, 2024. Retrieved 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. Assessing age at death in Niemann-Pick disease type C: using disease support group websites to understand the natural history of the disease. Mol Genet Metab. 2019;126(4):466-469. doi:10.1016/j.ymgme.2019.02.004}