Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann–Pick type C disease: review of initial published cases

Abstract

Niemann-Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-β-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-β-CD was 14 years (range 2-49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-β-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-β-CD in NP-C.

Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

“…Another orphan drug of HP-β-CD was designated by FDA in February 2013, Kleptose™ (brand VTS-270). Both drugs were being evaluated in clinical trials, moreover compassionate use outside clinical trials has been reported worldwide [32].…”

“…After 18 months of therapy, any objective improvement was reported, and the disease continued to progress as evidenced by positron emission tomography (PET) imaging and neurological assessments [26]. Both patients were described a transient appearance of slight scattered nodules in lungs during bronchoscopy, which were identified as xanthomas, a deposition of yellowish cholesterol-rich material typical of NPD-C, resolved without treatment changes in IV therapy [32].…”

“…In October 2010, the FDA allowed the addition of HP-β-CD IT administration at doses of 350 mg every 2 weeks (initial dose 175 mg/2 weeks) [32,33]. During the first months of concurrent IV/IT therapy, a significant improvement was observed in the validated NIH NPC Clinical Severity Score (NNCSS), as well as in the brainstem auditory evoked response (BAER) [33].…”

“…One of them tolerated perfectly the ICV and continues today with the treatment, whereas in her sister, ICV was discarded by insertion bleeding and IT route was recovered. Both patients have experienced improvements in alertness, swallow, head control, and ataxia [32,34].…”

News on the journal Neurological Sciences in 2017

“…Many reports are dedicated to rare neurologic diseases, genetic disorders describing new developments on the molecular diagnosis [121][122], the clinical heterogeneity of the clinical spectrum [123][124][125][126][127][128][129][130][131][132][133][134], and the therapeutic opportunities [135][136][137].…”