FDA Approves First Niemann-Pick Type C Treatment

SILVER SPRING, MD, USA I September 20, 2024 I

The U.S. Food and Drug Administration (FDA) has approved Miplyffa (arimoclomol), an oral medication, for treating Niemann-Pick disease, type C (NPC). This approval marks the first time the FDA has approved a drug for NPC. Miplyffa, used in combination with the enzyme inhibitor miglustat, addresses neurological symptoms in patients aged two years and older.

NPC is a rare genetic disorder that leads to progressive neurological issues and organ dysfunction. Caused by mutations in the NPC1 or NPC2 genes, the disease disrupts the transport of cholesterol and other lipids within cells, leading to cellular malfunction and organ damage. The average life expectancy for those with NPC is approximately 13 years.

Janet Maynard, M.D., M.H.S., director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine (ORPURM) at the FDA’s Center for Drug Evaluation and Research, emphasized the significance of this approval. She noted that, despite extensive research, no approved treatments previously existed to meet the substantial needs of NPC patients. She believes that the approval of Miplyffa will greatly support those suffering from this severe disease.

Miplyffa was the first product application reviewed by the Genetic Metabolic Diseases Advisory Committee (GeMDAC) during its inaugural meeting in August. Formed in December 2023, GeMDAC advises on products for diagnosing, preventing, or treating genetic metabolic diseases.

The safety and effectiveness of Miplyffa were demonstrated in a randomized, double-blind, placebo-controlled 12-month trial involving patients aged two to 19 with a molecularly confirmed diagnosis of NPC. In the trial, 50 patients were randomly assigned to receive either weight-adjusted doses of Miplyffa (31 to 124 mg) or a placebo three times daily. Of these patients, 39 (78%) also received miglustat as part of their treatment.

Miplyffa's efficacy was evaluated using the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score, which measures disease progression by assessing ambulation, speech, swallowing, and fine motor skills. Higher scores on this scale indicate greater disease severity. The trial results showed that Miplyffa, compared to the placebo, resulted in a slower progression of the disease as measured by the R4DNPCCSS score.

However, Miplyffa's prescribing information includes a warning for hypersensitivity reactions such as hives and angioedema (skin swelling). Patients experiencing these side effects should discontinue use. Additionally, pregnant women or those planning to become pregnant should avoid using Miplyffa.

Common side effects of Miplyffa include upper respiratory tract infections, diarrhea, and weight loss. The medication, along with miglustat, should be taken orally with or without food, following the recommended dosage based on the patient's body weight.

The FDA granted Miplyffa several designations, including priority review, orphan drug, rare pediatric disease, fast track, and breakthrough therapy, recognizing its potential to address significant unmet medical needs.

Approval of Miplyffa was granted to Zevra Therapeutics.

The FDA, part of the U.S. Department of Health and Human Services, is responsible for ensuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, biological products, medical devices, the nation's food supply, cosmetics, dietary supplements, and products that emit electronic radiation. It also regulates tobacco products.