FDA clears first drug for Niemann-Pick disease

Zevra Therapeutics' Miplyffa has become the first medicine to be approved by the FDA for the ultra-rare genetic disorder Niemann-Pick disease.

The US regulator has cleared Miplyffa (arimoclomol), in combination with the enzyme inhibitor miglustat, to treat neurological symptoms in adults and children two years of age and older with Niemann-Pick type C (NPC).

The green light comes three years after a first attempt to get approval for arimoclomol for NPC was rejected by the FDA, when it was owned by Danish biotech Orphazyme. It was also turned down by the EMA around that time, causing Orphazyme to sell the programme in 2022 to KemPharm, which was renamed Zevra the following year.

NPC is caused by mutations in either the NPC1 or NPC2 genes, which are involved in transporting cholesterol and other lipids within cells. That leads to the accumulation of the lipids, damaging the cells, and causes a range of symptoms that can include neurological impairment, as well as liver and lung problems.

Janet Maynard, director of the FDA's Office of Rare Diseases, Paediatrics, Urologic and Reproductive Medicine (ORPURM), said that NPC is "a serious disease that leads to enormous adverse impacts on patients and families."

She added that, despite extensive research efforts, until now there have been no approved treatments, so the "first-ever approval of a safe and effective drug option for NPC will undoubtedly support the essential medical needs of those suffering."

The approval follows an FDA advisory committee meeting in August that concluded arimoclomol had modest clinical benefits and a favourable safety profile when combined with miglustat – a drug originally developed by Actelion as Zavesca for other diseases that is now available in generic form in the US and used off-label to treat NPC.

In its latest review, the FDA considered a 50-patient phase 2/3 trial run by Orphazyme that showed a slowdown in disease progression with Miplyffa, measured using 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 US within eight to 12 weeks. There's no word yet on price, although, more details may be available on a Zevra conference call scheduled to take place later today.

It is estimated that around 300 to 400 people in the US are diagnosed and/or miglustat-treated for NPC. The disease can be diagnosed at almost any age from infancy to adulthood, and is a highly variable disorder, with some patients having devastating symptoms early in life and others reaching adulthood undiagnosed as the effects are relatively mild.

The FDA had awarded arimoclomol priority review, orphan drug, rare paediatric disease, fast track, and breakthrough therapy designations for this application, reflecting the urgent need for treatment options.