Rafael Holdings Shares Fall 25% After Trappsol Cyclo Phase 3 Trial Misses Primary Endpoint

Rafael Holdings Inc Class B (NYSE:RFL) shares fell 25% in pre-market trading on Wednesday after the company’s Phase 3 TransportNPC trial of Trappsol Cyclo in patients with Niemann-Pick Disease Type C (NPC) failed to meet its primary endpoint.

The study enrolled 94 patients and evaluated the change from baseline in the 4-domain NPC Clinical Severity Scale at Week 96.

Trappsol Cyclo showed a directionally favourable treatment effect compared with placebo, slowing disease progression by 64%. However, the result did not reach statistical significance, with a p-value of 0.19.

Prespecified Subgroup Analysis Reaches Statistical Significance

A prespecified analysis of patients receiving background treatment with miglustat and/or leucine showed a statistically significant treatment effect.

The subgroup included 78 patients, representing approximately 83% of the TransportNPC study population.

Among these patients, Trappsol Cyclo slowed disease progression by 71% compared with placebo at Week 96, with a p-value of 0.046.

The subgroup result was separate from the overall study’s primary endpoint, which did not achieve statistical significance.

No New Safety Signals Reported

Rafael Holdings said Trappsol Cyclo demonstrated a safety profile consistent with previous studies, with no new safety signals identified.

Treatment-emergent adverse events were reported in 93.8% of patients receiving Trappsol Cyclo compared with 100% of patients receiving placebo.

Serious treatment-related adverse events occurred in 3.1% of the Trappsol Cyclo group and 3.3% of the placebo group.

Separate Analysis Examines Overall Survival

Rafael Holdings also conducted a separate overall survival analysis involving patients with infantile-onset NPC treated with Trappsol Cyclo.

The analysis compared treated patients with matched external controls from the International Niemann-Pick Disease Registry.

According to the analysis, treatment with Trappsol Cyclo was associated with an 85% reduction in the risk of mortality compared with the matched external controls.

The survival analysis was separate from the randomised Phase 3 trial’s primary endpoint and used external controls rather than the study’s placebo group.

New Drug Application Planned for Fourth Quarter

Despite the TransportNPC study not meeting its primary endpoint, Rafael Holdings remains on track to submit a New Drug Application for Trappsol Cyclo in the fourth quarter of 2026.

The planned submission follows the company’s previously announced pre-NDA meeting with the U.S. Food and Drug Administration.

Rafael Holdings shares fell 25% in pre-market trading following publication of the Phase 3 results.

Rafael Holdings stock price