Cyclo NPC1 Phase 1/2 Trial Hits Primary Endpoint

Rare Daily Staff

Cyclo Therapeutics said topline data from its phase 1/2 clinical trial of Trappsol Cyclo in the treatment of the rare genetic disease Niemann-Pick Disease type C1 met its primary endpoint.

“These data continue to underpin our strong belief that Trappsol Cyclo has the ability to be a safe and effective treatment for both systemic and neurologic manifestations of NPC,” said N. Scott Fine, CEO of Cyclo Therapeutics. “And, the data have informed our phase 3 clinical trial design, allowing us to move forward with great confidence in the next crucial stage of drug development to meet the unmet need in the NPC community.”

Niemann-Pick Disease Type C1 is a rare genetic disease affecting 1 in 100,000 live births globally. NPC1 affects every cell in the body due to a defect in the NPC1 protein which is responsible for cholesterol processing in the cell. NPC causes symptoms in the brain, liver, spleen, lung and other organs and often leads to premature death. There are no approved drug therapies for NPC in the United States and only one approved therapy in Europe.

Trappsol Cyclo, the company’s proprietary formulation of hydroxypropyl beta cyclodextrin, has orphan drug designated product in the United States and Europe.

The multi-center, randomized, double-blind, parallel group trial without a placebo arm randomized 12 patients ranging in age from 2 to 39 years across clinical sites in the United Kingdom, Israel, and Sweden. Patients were treated intravenously with Trappsol Cyclo over 8 to 9 hours for a total of 24 doses in a 48-week treatment period. Three doses of Trappsol Cyclo were evaluated.

Of the nine patients who completed the study, eight met the first efficacy endpoint. Patients improved in disease-related domains that included the ability to walk, speak, swallow, behavioral features, incontinence, fine motor skills, saccadic eye movements, and cognition.

The 17-domain NPC Severity Scores for all patients between baseline and last available assessment showed overall improvement in six patients and worsening in five. One patient had only baseline data and was excluded from the analysis. Based on natural history data with no intervention, patients would be expected to decline on average by 1.5 points over this time period. The three patients who were withdrawn from the study by treating physicians worsened by 6 and 8 points at their last assessment or had a single baseline score.

NPC patients and caregivers report that improvement in any one of the following five domains would enhance their quality of life: ambulation, speech, swallow, fine motor skills and cognition. Of the nine patients who completed the trial, six improved in at least one of these domains, and two improved in two of the domains. Further, 67 percent showed improvement or stabilization in the total score of these five domains.

Of the nine patients who completed the study, all were rated as either improved or stable by clinicians at the end of the study. Clinicians rated seven patients as improving to some degree at 48 weeks, with two patients as stable.

The pharmacodynamic endpoints measured in this study suggest that Trappsol Cyclo clears cholesterol from cells and normalizes cholesterol metabolism. Serum lathosterol, an indicator of whole-body cholesterol synthesis, was reduced by 44 percent across all patients on average between baseline and two days after the first infusion, indicating that cholesterol synthesis was suppressed, most likely due to the release of trapped cholesterol.

All dose groups showed a favorable safety profile, consistent with previously reported data from a companion phase 1 clinical trial. Serious adverse events were reported in five patients. Of these, three were considered by the investigator to be at least possibly related to the study drug: one hearing related event resolved within a month. The two other events were in a pediatric patient related to infiltrated peripheral cannula which resolved quickly, and which did not interfere with study completion.

Nine patients completed the trial and three were withdrawn by treating physicians. One patient was withdrawn at Week 24 due to intercurrent illness, another who had completed the 36 Week assessment was withdrawn due to COVID-19 travel restrictions which prohibited further participation. The third patient’s parents refused to consent for efficacy assessments prior to Week 12, and the patient was withdrawn from the study and not replaced in keeping with the protocol. No patient was withdrawn due to concerns over safety of the drug.

Photo: N. Scott Fine, CEO of Cyclo Therapeutics