Rafael Holdings Reports 78% Success Rate for NPC1 Treatment in Phase 3 Pediatric Sub-Study
Key Insights
Rafael Holdings (search) announced preliminary data from its Phase 3 TransportNPC sub-study showing that 7 of 9 patients under 3 years old with NPC1 (search) demonstrated stabilization or improvement after 48 weeks of treatment with Trappsol Cyclo.
The investigational drug hydroxypropyl-beta-cyclodextrin showed a favorable safety profile with the majority of adverse events reported as mild to moderate, and no serious adverse events were considered related to the study drug.
The data was presented at the 15th International Congress of Inborn Errors of Metabolism, representing the first clinical evidence for treating NPC1 (search) in this youngest patient population over a 48-week period.
Rafael Holdings (search) announced promising preliminary results from its Phase 3 TransportNPC sub-study evaluating Trappsol Cyclo (hydroxypropyl-beta-cyclodextrin) in the youngest patients with Niemann-Pick Disease Type C1 (search) (NPC1 (search)). The data, presented at the 15th International Congress of Inborn Errors of Metabolism, showed that 7 of 9 patients under 3 years old demonstrated stabilization or improvement in their Clinical Global Impression-Severity (CGI-S) scores after 48 weeks of treatment.
Clinical Outcomes in Youngest Patient Population
The open-label, single-arm sub-study enrolled ten patients from birth to 3 years of age, with two patients terminating participation after 48 weeks due to caregiver decisions. Among the nine patients who completed 48 weeks of treatment, three showed improvement in their CGI-S scores, four demonstrated stabilization, and two experienced deterioration.
Dr. Orna Staretz-Chacham, Senior neonatologist and metabolic specialist at Soroka Medical Center and Principal Investigator for the TransportNPC study, presented the findings. "This growing body of promising preliminary findings from the TransportNPC sub-study continues to strengthen the potential of Trappsol Cyclo to address the significant unmet medical need in the treatment of NPC1 (search)," she commented.
At baseline, the sub-study patients presented with a mixture of very mild to severe disease based on the CGI-S scale, representing the spectrum of disease severity typically seen in this rare genetic disorder.
Safety Profile Consistent with Previous Studies
The safety data from the pediatric sub-study aligned with findings from earlier clinical trials. As of May 14, 2025, investigators recorded 146 adverse events, with 69% classified as mild and 29% as moderate. Only three events were reported as severe, while 14% were categorized as Serious Adverse Events (SAEs).
Importantly, no SAEs were considered by principal investigators as related to or possibly related to the study drug, supporting the treatment's safety profile in this vulnerable patient population.
Addressing Critical Unmet Medical Need
NPC1 (search) affects approximately 1 in 100,000 live births globally and often leads to premature death. The disease is characterized by an inability for cells to transport and process cholesterol, resulting in excessive cholesterol accumulation that damages the liver, spleen, and brain. Symptoms include progressive intellectual decline, loss of motor skills, seizures, and dementia.
Trappsol Cyclo is designed to directly impact the root cause of NPC1 (search) by mobilizing cholesterol from late-stage endosomes (search) and lysosomes (search). The investigational drug has demonstrated the ability to cross the blood-brain barrier after intravenous administration, suggesting therapeutic concentrations can be reached in the central nervous system.
Broader Phase 3 Program Context
The pediatric sub-study operates within Rafael Holdings (search)' comprehensive Phase 3 TransportNPC program, which represents the most extensive controlled pivotal study for NPC1 (search) treatment. The main study is a randomized, double-blind, placebo-controlled trial that enrolled 94 patients across over 25 sites in 13 countries.
The primary study evaluates 2,000 mg/kg doses of Trappsol Cyclo administered intravenously every two weeks compared to placebo, both in combination with standard of care. The study duration spans 96 weeks, with a 48-week comparative interim analysis that was successfully completed, allowing the trial to continue for its full duration.
Cyclo Therapeutics has received Orphan Drug Designation for Trappsol Cyclo in both the United States and European Union, along with Fast Track and Rare Pediatric Disease Designations in the U.S. The Rare Pediatric Disease Designation positions the company to potentially receive a Priority Review Voucher upon marketing authorization.
The pediatric sub-study data represents the first clinical evidence for treating NPC1 (search) with hydroxypropyl-beta-cyclodextrin in patients under 3 years of age over a 48-week treatment period, providing crucial insights for this particularly vulnerable patient population.