The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.

Interim unblinded analysis from a phase 1/2 trial evaluating hydroxypropyl beta cyclodextrin (Trappsol® Cyclo; Cyclo Therapeutics, Inc) for the treatment of patients with Niemann-Pick disease type C1 (NPC1) support the launch of a phase 3 global study, according to research presented at the 17th Annual WORLDSymposium.

NPC1 is a rare progressive genetic disorder characterized by an abnormal accumulation of cholesterol and other fatty substances in various tissues of the body, including brain tissue. In preclinical studies, hydroxypropyl beta cyclodextrin (HPbCDs) has been shown to transport cholesterol from cells, normalizing cholesterol metabolism. The combined data suggest that the investigational therapy has the potential to treat systemic and neurologic manifestations of NPC.

The ongoing phase 1/2 trial ( NCT02912793) evaluated the efficacy, safety, and pharmacokinetics of HPbCD in 12 patients aged 2 years and older with NPC1. Patients were randomly assigned 1:1:1 to receive a slow intravenous (IV) infusion of HPbCD 1500mg/kg, 2000mg/kg, or 2500mg/kg biweekly for 48 weeks.

Interim results showed that HPbCD was present in the cerebrospinal fluid during and after the end of IV infusion at all dose levels. Additionally, treatment with HPbCD showed a clear downward trend in lysosphingomyelin-509 in plasma with no apparent dose relationship. A reduction in tau, a neurodegeneration biomarker, was also observed in the cerebrospinal fluid of 3 patients who opted for additional lumbar punctures at 24 and 48 weeks, indicating the possibility of the drug providing a neuroprotective effect.

Among 7 patients who completed the trial as of September 2020, 6 patients (86%) met the first efficacy outcome measure related to improvement in 2 or more domains of the 17-Domain NPC Clinical Severity Scale measure. Moreover, 5 out of 7 patients showed improvement for the second efficacy outcome measure of global impression of disease at week 48 from baseline, using the Clinicians Global Impression of Improvement scale, while 2 remained stable.

To date, the cumulative safety data for HPbCD has shown it to be well tolerated with a favorable safety profile for all dose groups. There were 3 serious treatment-related adverse events, of which 2 were related to infusion and 1 related to hearing loss (grade 2) that resolved.

Study authors concluded, “HPbCD crosses the blood-brain barrier, and engages target cells peripherally and centrally shown by biomarkers for cholesterol metabolism and by tau in CNS.” They added, “These data support the launch of a phase 3 global pivotal trial.”

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Raiman JAJ, Sharma R, Paucar M, et al. Update on safety and efficacy results for phase I/II trial of hydroxypropyl betacyclodextrin (HPbCD) administered intravenously in patients with Niemann-Pick disease type C1. Presented at: 17th Annual WORLDSymposium; February 8-12, 2020. Poster #209.