Phase 2/3 Huntington's Disease Study Fails to Meet Primary Endpoint

James Radke, PhD

Company to Continue Talks With FDA and EMA To Hopefully Design a Confirmatory Study.

Results from Raptor Pharmaceutical’s phase 2/3 clinical trial testing the safety and efficacy of  RP103 (cysteamine) in Huntington's disease was announced today. And at the end of 36 months of treatment (18 months placebo controlled study, 18 months open label), the primary efficacy endpoint – change in baseline Total Motor Score (TMS) component of the Unified Huntington's Disease Rating Scale (UHDRS) – was not met.
While the results may be disappointing, a trend was observed and the company plans to continue with its discussions with the EMA and FDA to develop a confirmatory clinical trial that will lead to approval.
Julie Anne Smith, Raptor's President and CEO. Said, "We are excited to be advancing a treatment that has the potential to slow the rate of motor and functional decline in Huntington's disease patients," adding, "Such a therapy holds promise to be transformational for patients and is perfectly aligned with our strategic focus to develop and commercialize therapies that bring significant relief to patients and families living with life-threatening diseases. We look forward to discussing the 36-month data with the regulatory authorities and to advancing RP103 in a confirmatory study."
Principal investigator or the phase 2/3 study, Dominique Bonneau, M.D., Professor of Medical Genetics at the CHU d'Angers echoed that statement,  "The 36-month efficacy results from the CYST-HD study are clinically meaningful and suggest that RP103 may play an important role in the treatment of Huntington's disease," adding, "These data warrant further assessment as there remains a clear need for new, safe and tolerable therapies to treat this disease."


CYST-HD was a randomized, placebo-controlled, multi-center trial evaluating the long-term efficacy, safety and tolerability of RP103 for the treatment of Huntington's disease. In the first 18 months, patients with Huntington’s disease were randomized to receive RP103 (n=51) or placebo (n=45) then the placebo group patients were allowed RP103 for the remaining 18 months in the open label portion of the study.

The primary efficacy endpoint was the change from baseline at 18 months in the TMS component of the UHDRS between placebo/RP103 and RP103/RP103-treated subjects.

At the 18 month point, the differences in the TMS scores were not different between the two groups. At 36 months, when both groups are taking the RP103, the patients having taken RP103 for the entire 36 months showed a  25% slower progression of the disease based on TMS change from baseline (see graph below).

3 Suicides Reported

The most common adverse events included nausea, vomiting, diarrhea, headache and breath odor. Three deaths due to suicide occurred during the open-label period of the study. While concerning, Raptor stated that the suicide rate is consistent with historical data showing suicide to account for 5% to 7% of deaths in this population.


Raptor Plans to Advance RP103 in a Registration Study in Huntington's Disease Based on Favorable Treatment Effects at 36 Months in CYST-HD Trial [press release]. Novato, CA; December 10, 2015.
Figures obtained from Raptor’s investors’ conference call held December 10, 2015.
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