Treatment of Niemann-Pick Disease Type-C with 2-hydroxypropyl-β-cyclodextrin

Currently, there are no FDA-approved therapies for Niemann-Pick disease type-C1 (NPC). NPC is a rare lethal genetic lysosomal storage disorder that results in an accumulation of cholesterol in the liver and spleen and eventually leads to neurodegeneration. 2-hydroxypropyl-β-cyclodextrin (HPβCD) is a cyclodextrin typically used by the pharmaceutical industry as an excipient. Studies of NPC in animal models have shown that HPβCD can reduce the biochemical burden associated with NPC, improving neurological pathology, decreasing neurological dysfunction, and increasing lifespan. 

Development of an FDA approvable treatment for NPC has been advanced by the transfer of a proprietary formulation of HPβCD and access to the FDA drug master file from Janssen Research & Development, LLC (J&J/Janssen) to the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). 

Both NICHD and NCATS are recipients of material and technical support from J&J/Janssen. The company is providing its properietary FDA-approved formulation of HPβCD for use in both preclinical and clinical studies. J&J/Janssen’s HPβCD is made by a high-yield process; it is very well-characterized and has an FDA drug master file (DMF). In addition, this material was administered to two NPC patients in September 2010 under a “compassionate use” investigational new drug (IND) after the FDA granted HPβCD orphan drug status in May 2010. So the participation of J&J/Janssen in this project is critical to its success. 

Along with the material, J&J/Janssen is providing access to its DMF and toxicology expertise in support of an IND to be filed by NICHD. It is anticipated that, in the upcoming clinical trial, J&J/Janssen will also provide analytical laboratory support to the clinical trial to determine HPβCD metabolite levels in samples of patient biofluids. 

Importantly, J&J/Janssen is allowing NIH to reformulate its HPβCD and redistribute it to the academic collaborators as necessary to ensure the success of the project. 

The result of this technology transfer effort was the rapid accumulation of preclinical results in support of an IND application to the FDA for the use of HPβCD for treating NPC by intracerebroventricular (ICV) therapeutic administration. The further efforts of the collaborating parties will represent the best effort to advance FDA approval of a treatment for NPC. 

Awardees

NIH - Eunice Kennedy Shriver National Institute of Child Health and Human Development 

• Dr. Forbes D. Porter
• Nicole Yanjanin
• John Heiss

NIH - National Human Genome Research Institute 

• Bill Paven

NIH - National Center for Advancing Translational Sciences

• Dr. Christopher P. Austin 
• Dr. John McKew 
• Dr. Elizabeth Ottinger 
• Lili Portilla 
• Dr. Juan Jose Marugan 
• Dr. Wei Zheng 
• Dr. Nuria Carillo-Carrasco 
• Xin Xiu 
• Pramod Terse

NIH - National Cancer Institute

• Dr. Alan E. Hubbs

J&J Pharmaceutical Research & Development, LLC

• Dr. Steven Silber
• Dr. L. Mark Kao
• Ilona Scot