Rafael files remibetadex for Niemann-Pick type C despite a missed primary endpoint

Rafael Holdings has submitted a new drug application to the FDA for remibetadex, the intravenous hydroxypropyl-beta-cyclodextrin previously known as Trappsol Cyclo, for Niemann-Pick disease type C (NPC). The filing, announced on 29 October 2026 by its subsidiary Cyclo Therapeutics, seeks approval for the neurovisceral manifestations of the disease in adult and paediatric patients from birth.

NPC is a rare, progressive genetic disorder whose most severe form begins in infancy. The drug holds orphan, fast track and rare pediatric disease designations. The FDA has 60 days to decide whether to accept the application and whether to grant priority review.

What the trial showed

The application rests mainly on TransportNPC, a double-blind, placebo-controlled phase 3 study that enrolled 94 patients aged 3 to 70. Patients received 2,000 mg/kg intravenously every two weeks (63 patients) or placebo (31) for 96 weeks.

The primary endpoint was the change in a four-domain NPC clinical severity scale at week 96. Scores worsened by 0.46 points on remibetadex and 1.28 points on placebo, a difference of 0.81 points with a confidence interval that crossed zero and a p-value of 0.19. Rafael describes this as a 64% slowing of progression, but acknowledged when it reported topline results on 30 September that the result did not achieve statistical significance. Its shares fell by about a third that day.

Where the case rests

Rafael points instead to a prespecified analysis of the 78 patients, about 83% of the trial, who were also taking miglustat and/or leucine. In that group the difference was 1.11 points (p=0.046), described as a 71% slowing.

The company also submitted an overall survival analysis in infantile-onset NPC, comparing 41 treated patients with 93 matched controls from an international registry. It reported a hazard ratio of 0.154, an 85% reduction in the risk of death (p=0.044). That comparison sits outside the randomised trial.

A subgroup and an external control can support a filing, but they rarely carry one on their own.

Safety and what comes next

Serious adverse events were reported in 35.9% of patients on remibetadex against 16.7% on placebo. Hearing-related adverse events occurred in 15.6% and 13.3% respectively, mostly mild or moderate, with one severe, treatment-related case of bilateral deafness. Rafael says no new safety signals were seen.

For the FDA, the application is a test of how far it will lean on supportive evidence in an ultra-rare disease after a failed primary endpoint. For Rafael there is a further prize: the company notes that approval would make remibetadex eligible for a rare pediatric disease priority review voucher.