Rafael’s Drug Slows Niemann-Pick Disease Progression by 64% in Trial That Missed Statistical Significance on Primary Endpoint
Key Facts
Rafael Holdings announced on September 30, 2026, results from the Phase 3 TransportNPC trial of Trappsol Cyclo, which included 94 patients with Niemann-Pick disease type C, aged 3 to 70. The company said the drug slowed disease progression by 64% compared with placebo at week 96, but the primary endpoint did not reach statistical significance, with a p-value of 0.19. This puts the results in a mixed context: a signal of slower disease progression, without statistical proof on the trial’s primary measure. A prespecified analysis of a group receiving background therapy also showed a statistically significant effect. The company additionally reported a separate survival analysis in patients whose disease began in childhood, compared with external controls.
The treatment group included 63 patients who received 2000 mg/kg intravenously every two weeks, while 31 patients received placebo for 96 weeks. At the primary endpoint at the end of that period, disease progression was slowed by 64% compared with placebo, but the p-value of 0.19 means the difference was not statistically significant. The percentage alone therefore does not constitute a conclusive positive trial result, and it would not be accurate to say the drug’s efficacy on the primary endpoint was proven. The comparison was based on a randomized trial with treatment and placebo groups. The primary endpoint remains the most important focus when assessing Phase 3 data.
In a prespecified analysis of 78 patients receiving miglustat and/or leucine, Rafael said disease progression was slowed by 71% compared with placebo at week 96, with a p-value of 0.046. This group represented about 83% of the study population, according to the company, and showed a statistically significant effect on the 4DNPCSS measure. This result differs from the overall group reading: it applies to patients receiving background therapy, while the trial’s primary endpoint did not achieve statistical significance. The analysis makes concomitant treatment an important part of interpreting the results, while remaining an analysis of a prespecified subgroup within the trial. The data provided did not report a corresponding result for a group not receiving background therapy.
On safety, serious adverse events occurred in 35.9% of patients who received Trappsol Cyclo, compared with 16.7% on placebo during the study. Serious events that the company linked to treatment were reported in 3.1% of the drug group and 3.3% of the placebo group. This distinction separates the total number of serious events from those classified as treatment-related. Safety adds another dimension to the assessment of results, alongside the difference between the primary endpoint and the prespecified analysis. The company provided these figures for the 96-week study period.
In a separate survival analysis of patients whose disease began in childhood, the company compared 41 patients treated with the drug with 93 matched controls from the INPDR registry. Treatment was associated with an 85% lower risk of death, with a hazard ratio (HR) of 0.154 and a p-value of 0.044. This was an observational comparison with external controls, not a randomized result from TransportNPC, so it stands as a separate supporting signal from the Phase 3 primary endpoint. In a broader secondary analysis using 133 historical controls, treatment was associated with a 94% lower risk of death, with an HR of 0.057 and a p-value of 0.0008. These analyses remain separate from the randomized comparison, whose primary endpoint failed to reach statistical significance.
Trappsol Cyclo is being assessed in a treatment area where drugs have already been approved. On September 20, 2024, the U.S. Food and Drug Administration approved Miplyffa to treat Niemann-Pick disease type C, describing it as the first drug approved for the disease. Four days later, on September 24, the agency approved Aqneursa for adults and children weighing at least 15 kilograms, saying it was the second treatment approved for the disease in a week. The new drug candidate therefore faces a regulatory landscape that includes two approved treatments. The evidence presented here did not specify what Trappsol Cyclo might add compared with available treatments.
Rafael announced on June 10, 2026, that the last patient had completed the final visit after 96 weeks, and said it had held a pre-IND meeting with the U.S. Food and Drug Administration and expected to submit a licensing application in the second half of the year. In its September results announcement, the company said it was targeting an NDA submission in the fourth quarter of 2026 following a pre-submission meeting, and intended to present the full results at an upcoming medical meeting. It added that data on the primary endpoint, the full dataset and the overall survival analysis remained subject to full analysis and regulatory review. In trading, Rafael shares closed at $1.21 on October 28, 2026, compared with $1.24 in the previous session. The closing-price data alone do not establish that the move was a response to any regulatory news.