Target Health Blog

Experimental Treatment For Niemann-Pick Disease Type C1

October 9, 2017

Orphan Disease

Niemann-Pick disease type C1 (NPC1) is a rare genetic disorder that primarily affects children and adolescents, causing a progressive decline in neurological and cognitive functions. The U.S. Food and Drug Administration has not approved any treatments for the condition.

According to an article published in The Lancet (10 August 2017), an experimental drug appears to slow the progression of NPC1. The drug, 2-hydroxypropyl-beta-cyclodextrin (VTS-270), is being tested under a cooperative research and development agreement, or CRADA, between NIH and Sucampo Pharmaceuticals. In April 2017, Sucampo acquired Vtesse Inc., which previously had been developing VTS-270.

The study was a phase 1/2a clinical trial designed to test the drug's safety and effectiveness. A group of 14 participants, ranging from ages 4 to 23 years, received the experimental drug once a month at NIH for 12 to 18 months. Another group of three participants received the drug every two weeks for 18 months at Rush University Medical Center in Chicago. Initially, participants were divided into groups receiving different doses of the drug, but after observing that the drug was safe and well-tolerated by those receiving the highest doses, the dose was increased for all participants. Clinical progress was compared to a previous group of 21 NPC1 participants enrolled in an earlier study that documented disease progression.

In terms of safety, no serious adverse outcomes related to the drug were observed. However, the participants, most of whom had already experienced hearing loss because of the disease, had additional hearing loss after treatment. Earlier studies had shown that the treatment carries the risk for hearing loss. In the current study, hearing loss was compensated with hearing aids, which enabled participants to go about their daily lives. Because NPC1 symptoms result from cholesterol buildup in brain cells, the authors also measured cholesterol metabolism in the participants' central nervous system. Results showed that after treatment, a molecule derived from cholesterol metabolism in neurons, 24(S)-hydroxycholesterol, had increased. In addition, most participants had lower levels of two proteins indicative of brain injury, FABP3 and calbindin D, implying that there was less damage in the brain. According to the study authors, these results suggest that VTS-270 can improve cholesterol metabolism in neurons, thereby targeting the root of the problem. The authors also evaluated the drug's effectiveness using a neurological severity score, where higher scores indicate more severe effects from the disease. Compared to an earlier group of patients who had not received the drug, VTS-270-treated participants had lower scores in measures of cognition and speech, with mobility scores also trending lower. The authors believe these differences indicate that treatment with the drug can stabilize or slow disease progression.

NICHD researchers led the design, data collection and analysis of the phase 1/2a clinical trial. VTS-270 was provided by Janssen Research & Development, a Johnson & Johnson company. Researchers are now working on a randomized, controlled phase 2b/3 clinical trial (NCT02534844) has been approved by the FDA and the European Medicines Agency. The trial is sponsored by Sucampo, and its results will help determine which symptoms are most responsive to the drug and provide information for refining the dose and dosing frequency. The goal of this trial is to obtain regulatory approval of VTS-270.

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