A key phase 3 trial for Trappsol Cyclo in Niemann-Pick disease type C (NPC) failed to meet its primary endpoint, though the drug showed signs of slowing disease progression in a key subgroup. Rafael Holdings announced topline results from the TransportNPC trial, which tested the intravenous treatment against placebo over 96 weeks. The study enrolled 94 patients aged 3 to 70, with 63 receiving Trappsol Cyclo and 31 placebo.
Missed primary goal, but subgroup results stand out
The trial’s primary measure, the 4-domain NPC Clinical Severity Scale (4DNPCSS), showed a 0.46-point mean change in the treatment group versus 1.28 points for placebo. The difference of -0.81 points was not statistically significant (P = 0.19), though it corresponded to a 64% slowing of disease progression. However, a prespecified subgroup of 78 patients, those also taking miglustat, leucine, or both, showed stronger separation. Here, the treatment group’s mean change was 0.46 points versus 1.57 points for placebo, a -1.11-point difference (P = 0.046), equating to a 71% slowing in progression.
Caroline Hastings, MD, a professor of pediatric hematology and neurology at UCSF Benioff Children’s Hospital Oakland, called the subgroup findings “clinically meaningful.” She noted the study’s rigor and alignment with earlier trials over a decade of development. “Preserving function and stabilizing symptoms are critical” for patients with this rare, degenerative disease, she said.
Safety profile consistent with prior studies
Adverse events were common in both groups, with 93.8% of Trappsol Cyclo patients and 100% of placebo patients reporting treatment-emergent events. Serious adverse events occurred more often in the treatment arm (35.9% vs 16.7%), though treatment-related serious events were nearly identical (3.1% vs 3.3%). No deaths were reported, and only one patient discontinued due to an adverse event.
Hearing-related issues were slightly more frequent in the treatment group (15.6% vs 13.3%), with most cases mild to moderate. One severe case of bilateral deafness was reported as treatment-related. The company described the safety profile as consistent with earlier studies, with no new warning signals.
Survival data hints at broader benefits
A separate analysis of 41 infantile-onset NPC patients treated with Trappsol Cyclo showed a 85% reduction in mortality risk compared to matched controls from the INPDR registry. Against a larger historical cohort, the risk dropped by 94%.
Karen Mullen, MBBS, Rafael Holdings’ chief medical officer, emphasized the “totality of the data” as a rationale for advancing the drug, despite the primary endpoint miss. The company plans to submit a new drug application (NDA) in the fourth quarter of 2026, following a pre-NDA meeting with the FDA. Full results will be presented at an upcoming medical conference.
