Posted by Niemann-Pick disease type C (NPC) is a rare, fatal, pan-ethnic, autosomal recessive lysosomal storage disease characterized by progressive major organ failure and neurodegeneration. Preclinical studies confirmed a critical role of systemically administered hydroxypropyl-β-cyclodextrin (HP-β-CD; Trappsol® Cyclo™) in cholesterol metabolism and homeostasis in peripheral tissues of the body, including the liver, and in the central nervous system (CNS). Herein, the pharmacokinetics (PK), safety, and efficacy of HP-β-CD, and biomarkers of NPC were assessed in pediatric and adult patients with NPC1.
Nine patients completed the study, 2 in the 1500 mg/kg group, 4 in the 2000 mg/kg group and 3 in the 2500 mg/kg group. Three patients (all in the 1500 mg/kg group) discontinued the study because of either physician decision/site Principal Investigator (PI) discretion, withdrawal by subject/patient/parent/ guardian, or other non-safety reasons. In 5 patients who underwent serial lumbar punctures, HP-β-CD was detected in the CSF. Of the 9 patients who completed the study, 8 (88.9%) improved in at least two domains of the 17-Domain Niemann-Pick disease Type C-Clinical Severity Scale (17D-NPC-CSS), and 6 of these patients improved in at least one domain viewed by patients and their caregivers to be key to quality of life, namely, speech, swallow, fine and gross motor skills, and cognition. Of the 9 patients who completed the study, 7 were viewed by their treating physicians as having improved to some degree at the end of the study, and 2 remained stable; both outcomes are highly relevant in a progressive neurodegenerative disease. Some patients and families reported improvement in quality of life.
All three doses of HP-β-CD were well tolerated overall, with most treatment-emergent adverse events transient, mild-to-moderate in nature, and considered by the site PIs to be not related to study drug.
Reena Sharma, Caroline Hastings, Orna Staretz-Chacham, Julian Raiman, Martin Paucar, Ronen Spiegel, Bryan Murray, Bryan Hurst, Benny Liu, Lise Kjems, Sharon Hrynkow,
Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial
Molecular Genetics and Metabolism Reports 36, 2023, 100988,
https://doi.org/10.1016/j.ymgmr.2023.100988.