Rafael Holdings completes Phase 3 enrolment for NPC drug Trappsol Cyclo

Rafael Holdings has announced that the final patient has completed the 96-week study visit in its pivotal Phase 3 TransportNPC trial of Trappsol Cyclo (hydroxypropyl beta-cyclodextrin) for Niemann-Pick Disease Type C (NPC). The study enrolled 94 patients across 27 sites in 13 countries, making it, by the company's account, the largest and most geographically comprehensive controlled trial ever conducted in NPC. Topline results from the main cohort are expected to be disclosed in the second half of 2026.

The NYSE-listed company said it has already held a pre-NDA meeting with the US Food and Drug Administration and intends to file a New Drug Application also in H2 2026. The FDA has separately acknowledged that Rafael's US Expanded Access Programme for Trappsol Cyclo may continue, providing a route to treatment for eligible patients ahead of any formal approval decision.

Paediatric sub-study data

Alongside the pivotal readout, Rafael presented data at WORLDSymposium 2026 from a ten-patient single-arm sub-study conducted under its adopted Paediatric Investigational Plan. The sub-study covers patients from birth to three years of age — an age band where disease progression can be particularly rapid. Results showed that 80% of sub-study participants recorded improvements or stability on the Clinical Global Impression scale, with no serious adverse events attributed to the study drug. While the cohort is small and the study lacks a control arm, the safety and preliminary efficacy signal is likely to feature prominently in the NDA package.

Chief executive Howard Jonas said the company believes it has "a clear and expedited path forward reflective of the urgency and unmet need in NPC," and described a potential transition to commercial-stage operations as a strategic priority.

Regulatory and competitive context

NPC is a rare, fatal lysosomal storage disorder caused primarily by mutations in the NPC1 gene, leading to intracellular cholesterol trafficking defects. The disease has historically had no approved disease-modifying therapy in the United States, though miglustat — approved in Europe and some other markets as a substrate reduction therapy — has been used off-label. That therapeutic gap underpins the FDA's longstanding engagement with Rafael's programme, which has benefited from Orphan Drug and Breakthrough Therapy designations.

The competitive landscape for rare lysosomal storage diseases has broadened considerably in recent years. Gene therapy approaches targeting NPC1 are at preclinical and early clinical stages at several academic centres and smaller biotechs, and substrate reduction strategies remain an area of active research. Hydroxypropyl beta-cyclodextrin works through a distinct mechanism — facilitating cholesterol egress from late endosomes and lysosomes — and, if approved, would be the first NDA-approved therapy specifically indicated for NPC in the US market.

Investors will be focused on the topline readout expected later this year, particularly the primary efficacy endpoint design and whether the trial is powered sufficiently to demonstrate a meaningful treatment effect across a heterogeneous rare-disease population. Given the pre-NDA meeting is complete and the regulatory dialogue appears constructive, the principal remaining variable is the data itself. A PDUFA date would follow NDA acceptance, typically six to twelve months after submission under standard or priority review timelines.