Newark, New Jersey-based Rafael Holdings, Inc. (NYSE: RFL) reported topline Phase III results for Trappsol Cyclo in Niemann-Pick disease type C (NPC), with the pivotal study missing its primary efficacy endpoint overall but showing a statistically significant benefit in a prespecified subgroup. Despite the missed endpoint, Rafael said it remains on track to submit a New Drug Application to the US FDA in Q4 2026 following a pre-NDA meeting.
NPC is a rare, progressive and ultimately fatal genetic disorder in which impaired intracellular cholesterol trafficking leads to accumulation of lipids in organs including the brain, liver and spleen. Trappsol Cyclo is an intravenous formulation of hydroxypropyl beta cyclodextrin designed to mobilize cholesterol trapped within cellular lysosomes so it can be processed and cleared.
The global, double-blind TransportNPC study enrolled 94 patients aged 3 to 70 years who received Trappsol Cyclo or placebo every two weeks for 96 weeks. Across the full study population, patients receiving Trappsol Cyclo worsened more slowly on a four-domain NPC clinical severity scale than those receiving placebo, but the difference was not statistically significant. Rafael described the result as a 64% slowing of disease progression.
A clearer treatment effect emerged in the prespecified subgroup of patients already receiving background miglustat and/or leucine, representing about 83% of participants. In that group, Trappsol Cyclo produced a statistically significant slowing of progression versus placebo, which Rafael characterized as a 71% reduction in worsening.
The overall primary-endpoint miss remains an important limitation because the subgroup finding does not replace the result in the full randomized population. Rafael said it nevertheless plans to include the Phase III data, along with supportive survival analyses and earlier clinical evidence, in its planned FDA submission.