Rafael Holdings Announces Pivotal Phase 3 Results for Trappsol® Cyclo™ in NPC

Rafael Holdings, Inc. has announced the topline results from its pivotal Phase 3 TransportNPC™ study evaluating Trappsol® Cyclo™ in patients with Niemann-Pick Disease Type C (NPC). The study, which enrolled 94 patients ranging in age from 3 to 70 years, did not achieve statistical significance for its primary endpoint, but demonstrated a directionally favorable treatment effect. Specifically, Trappsol® Cyclo™, an intravenous hydroxypropyl-β-cyclodextrin, showed a slowing of disease progression by 64% on the 4-domain NPC Clinical Severity Scale (4DNPCSS) at Week 96 compared to placebo. The primary endpoint analysis, however, did not reach statistical significance, with a p-value of 0.19.

A prespecified analysis focusing on patients receiving background miglustat and/or leucine therapy, which represented approximately 83% of the study population, showed a statistically significant and clinically meaningful treatment benefit. In this subgroup, Trappsol® Cyclo™ slowed disease progression by 71% compared to placebo, with a p-value of 0.046. The analysis revealed a statistically significant difference in the 4DNPCSS change from baseline of 0.46 vs 1.57 points, with a difference of −1.11 points [95% CI −2.19, −0.02].

The safety and tolerability profile of Trappsol® Cyclo™ was well tolerated, consistent with previous studies. Adverse events were largely consistent with the underlying disease, with treatment-emergent adverse events (TEAEs) reported in 93.8% of participants receiving Trappsol® Cyclo™ and 100.0% of those receiving placebo. Serious TEAEs occurred more frequently with Trappsol® Cyclo™, at 35.9%, compared to 16.7% with placebo. However, serious TEAEs considered related to treatment were reported at similar rates, 3.1% for Trappsol® Cyclo™ and 3.3% for placebo. Hearing-related TEAEs were reported by 15.6% of participants receiving Trappsol® Cyclo™ and 13.3% receiving placebo, with most being mild or moderate in severity. One treatment-related event of bilateral deafness in the Trappsol® Cyclo™ group was severe.

The company also conducted a separate overall survival analysis comparing patients with infantile-onset NPC treated with Trappsol® Cyclo™ across its clinical development program with well-matched external controls from the International Niemann-Pick Disease Registry (INPDR). The analysis indicated a 85% reduction in the risk of mortality for patients treated with Trappsol® Cyclo™ compared to matched INPDR controls, with a hazard ratio of 0.154; 95% CI: 0.025-0.950; p=0.044. In a secondary analysis that expanded the control group to include additional matched historical cohorts from published natural history studies, treatment with Trappsol® Cyclo™ was associated with a 94% reduction in the risk of mortality, with a hazard ratio of 0.057; 95% CI: 0.011-0.306; p=0.0008.

Based on the results, Rafael Holdings remains on track to submit an NDA for Trappsol® Cyclo™ to the U.S. Food and Drug Administration in the fourth quarter of 2026, consistent with prior guidance. The company will host an investor conference call and webcast today, September 30, at 8:30 a.m. ET, to discuss the results in more detail.