Trappsol Cyclo showed a favorable Phase 3 treatment effect in Niemann-Pick disease type C, with statistical significance in a prespecified subgroup.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
Rafael Holdings reported topline results from the pivotal Phase 3 TransportNPC study of Trappsol Cyclo, an intravenous formulation of hydroxypropyl-β-cyclodextrin, in 94 patients with Niemann-Pick disease type C (NPC). The treatment produced a directionally favorable effect on the primary endpoint, but the overall result did not reach statistical significance. A prespecified analysis of patients receiving background miglustat and/or leucine showed a statistically significant improvement in disease progression.
Phase 3 Study Evaluated Disease Progression Over 96 Weeks
The global, double-blind, placebo-controlled CTD-TCNPC-301 study enrolled patients aged 3 to 70 years with NPC. Participants were randomized to receive Trappsol Cyclo at 2,000 mg/kg intravenously every two weeks or placebo for 96 weeks.
The primary endpoint was the change from baseline in the four-domain NPC Clinical Severity Scale (4DNPCSS), a measure used to assess disease progression.
At Week 96, the least-squares mean change in 4DNPCSS was 0.46 points with Trappsol Cyclo compared with 1.28 points with placebo. The company reported a 64% slowing of disease progression, with a treatment difference of 0.81 points. However, the result was not statistically significant (p=0.19).
Prespecified Background-Therapy Analysis Reached Statistical Significance
A prespecified analysis included 78 patients receiving background miglustat and/or leucine, representing approximately 83% of the study population.
In this subgroup, the least-squares mean change in 4DNPCSS was 0.46 points with Trappsol Cyclo versus 1.57 points with placebo. The reported treatment difference was 1.11 points, corresponding to a 71% slowing of disease progression and reaching statistical significance (p=0.046).
Safety Profile Remained Consistent with Earlier Studies
Trappsol Cyclo was generally well tolerated during the 96-week treatment period, with no new safety signals reported. Treatment-emergent adverse events occurred in 93.8% of patients receiving Trappsol Cyclo and 100% of those receiving placebo.
Serious adverse events occurred more frequently with Trappsol Cyclo than placebo, at 35.9% versus 16.7%. However, treatment-related serious adverse events were similar between groups, at 3.1% and 3.3%, respectively.
Hearing-related adverse events occurred in 15.6% of patients receiving Trappsol Cyclo and 13.3% receiving placebo. Most were mild or moderate, although one severe treatment-related case of bilateral deafness occurred in the Trappsol Cyclo group. No adverse events resulted in death, and one patient discontinued treatment because of an adverse event.
Survival Analysis Provides Additional Supportive Evidence
Rafael Holdings also reported a separate overall survival analysis in patients with infantile-onset NPC. The analysis compared 41 patients treated with Trappsol Cyclo across the clinical development program with matched external controls from the International Niemann-Pick Disease Registry.
Treatment was associated with an 85% lower risk of mortality versus 93 matched registry controls (HR 0.154; 95% CI, 0.025-0.950; p=0.044). An expanded analysis using 133 historical controls reported a 94% lower risk of mortality (HR 0.057; 95% CI, 0.011-0.306; p=0.0008). These analyses were observational comparisons with external controls and were presented as supportive evidence rather than results from the randomized Phase 3 comparison.
NDA Submission Planned for Fourth Quarter 2026
The company remains on track to submit a New Drug Application for Trappsol Cyclo to the FDA in the fourth quarter of 2026, following a previously announced pre-NDA meeting. The full dataset and survival analysis remain subject to further analysis and FDA review, and the company plans to present complete results at an upcoming medical meeting.
The Phase 3 findings therefore provide a mixed efficacy picture: the primary endpoint favored Trappsol Cyclo but did not achieve statistical significance, while the prespecified background-therapy subgroup reached statistical significance. The forthcoming NDA submission will place the complete clinical dataset under regulatory review.
Reference
Rafael Holdings Announces Topline Results from the Pivotal Phase 3 TransportNPC™ Study of Trappsol® Cyclo™ in Niemann-Pick Disease Type C (NPC), Rafael Holdings, 30 September 2026
Phase 3 Study to Evaluate Intravenous Trappsol(R) Cyclo (TM) in Pediatric and Adult Patients with Niemann-Pick Disease Type C1 (TransportNPC), ClinicalTrials.gov ID NCT04860960
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.