FDA approves first drug against Niemann-Pick disease

Miplyffa from Zevra Therapeutics is the first FDA-approved drug for the extremely rare genetic disorder Niemann-Pick disease.

The US regulator has approved Miplyffa (arimoclomol) in combination with the enzyme inhibitor miglustat for the treatment of neurological symptoms in adults and children aged two years and older with Niemann-Pick type C (NPC).

The green light comes three years after an initial attempt to get approval for arimoclomol for NPC, then owned by Danish biotech company Orphazyme, was rejected by the FDA. Around the same time, the EMA also rejected the application, prompting Orphazyme to sell the program in 2022 to KemPharm, which was renamed Zevra the following year.

NPC is caused by mutations in the NPC1 or NPC2 genes, which are involved in the transport of cholesterol and other lipids within cells. This leads to the accumulation of the lipids, damaging the cells and causing a range of symptoms, including neurological impairment and liver and lung problems.

Janet Maynard, director of the FDA's Office of Rare Diseases, Pediatrics, Urology and Reproductive Medicine (ORPURM), said NPC is “a serious disease that has a tremendous negative impact on patients and families.”

She added that despite extensive research efforts, there are still no approved treatments to date, so “the first approval of a safe and effective drug option for NPC will undoubtedly meet the essential medical needs of those affected.”

The approval followed an FDA advisory committee meeting in August that concluded that arimoclomol had modest clinical benefits and a favorable safety profile when combined with miglustat, a drug originally developed by Actelion under the name Zavesca for other diseases and now available in the U.S. as a generic drug used off-label to treat NPC.

In its recent review, the FDA considered a 50-patient Phase 2/3 study of Orphazyme that showed a slowing of disease progression with miplyffa (as measured by the R4DNPCCSS scale), as well as data from a four-year open-label extension and other supporting studies.

Zevra said Miplyffa will be commercially available in the U.S. within eight to 12 weeks. Pricing is not yet available, but more details could be announced on a Zevra conference call scheduled for later today.

It is estimated that approximately 300 to 400 people in the United States are diagnosed with NPC and/or are being treated with miglustat. The disease can be diagnosed at almost any age from infancy to adulthood and is a highly variable condition. Some patients experience devastating symptoms early on and others reach adulthood without a diagnosis because the effects are relatively mild.

The FDA granted arimoclomol Priority Review, Orphan Drug, Rare Childhood Disease, Fast Track and Breakthrough Therapy designations for this application, reflecting the urgent need for treatment options.