RP103 (DR Cysteamine) for Huntington's Disease

Huntington's Disease (HD) is a rare hereditary condition caused by a defective gene. This gene makes an abnormal protein which leads to the degeneration of certain nerve cells in the brain. Adult-onset HD, the most common form of this disorder, usually appears in patients who are in their early 30s or 40s.

There are few treatment options for HD. Drugs are available to help minimize some of the symptoms such as the uncontrollable movements and mood swings associated with HD. In preclinical studies, cysteamine has shown potential to slow the progression of HD (Shults 1986, Pinto 2005, Dubinsky 2006, Ferrer 2000).

Human and Preclinical Studies

The use of cysteamine in HD was first published in 1986 (Shults 1986). In 2005, Dr. Pinto and colleagues reported that cysteamine was beneficial to HD transgenic mice (Pinto 2005). In early 2006, Drs. Dubinsky and Gray found that cysteamine at 20 mg/kg per day was tolerable in patients with HD (Dubinsky 2006).

Dr. Borrell-Pages and colleagues reported their findings in 2006 regarding the mechanism of action of cysteamine, suggesting that cysteamine has a neuroprotective effect in HD mice because it increases the levels of BDNF (Ferrer 2000), a neuroprotective factor, in the brain. They also suggest that BDNF levels can be used as a biomarker of efficacy for cysteamine in HD (Borrell-Pages 2006). Biomarkers can be an important development issue when a therapy is used to prevent or slow clinical manifestation of a disorder.

Development Status for RP103 for Huntington's Disease

Centre Hospitalier Universitaire (CHU) d'Angers in France is conducting a clinical trial of RP103 called "CYST-HD Multicentre study of treatment of Huntington’s Disease with cysteamine, a randomized, controlled, double-blind multicenter phase II-III trial vs placebo."

The trial, in collaboration with Raptor, commenced in October 2010. Clinical researchers at CHU d’Angers, with input from researchers at the Curie Institute, have designed a protocol to investigate this potential mechanism in HD patients, using BDNF as a biomarker of potential efficacy.

Raptor is providing the clinical trial materials for this Phase 2 study, which is sponsored by CHU d’ Angers and funded by a grant from the French government. Eight clinical sites in France are enrolling 96 patients in a placebo-controlled, 18-month trial, followed by an open-label trial with all placebo patients rolling onto RP103 and all non-placebo patients continuing on RP103 for up to another 18 months. The primary end point of the trial will be based upon the Unified Huntington’s Disease Rating Scale, or UHDRS.

In 2008, Raptor received FDA orphan drug designation for cysteamine formulations, including RP103, for the potential treatment of HD.

Learn more about Raptor’s other clinical programs::

• RP103 for Nephropathic Cystinosis
• RP104 for Non-alcoholic Steatohepatitis (NASH)
• Convivia™ for ALDH2 Deficiency
• Tezampanel for Thrombotic Disorder

Phase 2 Clinical Trial of RP103 in Huntington's Disease Commenced

96 patients will be enrolled for an 18-month placebo-controlled study

Raptor Pharmaceutical Licenses Intellectual Property Related to Huntington's Disease

Raptor’s exclusive license from the Weizmann Institute of Science in Israel and Niigata University in Japan includes patents covering the use of transglutaminase inhibitors (molecules related to cysteamine) for the potential treatment of Huntington’s Disease and other neurological disorders.