Raptor Pharmaceuticals Announces Phase 2/3 Clinical Trial Results with Cysteamine (RP103) in Huntington’s Disease

Raptor Pharmaceuticals announced results from a planned 18 month analysis of an ongoing 3 year Phase 2/3 clinical trial of RP103 (delayed-release cysteamine) for the potential treatment of Huntington's disease (HD).  In HD animal models, there is evidence to suggest cysteamine may exert its beneficial effects by increasing the secretion of brain-derived neurotrophic factor (BDNF) in the brain.  BDNF levels are diminished in HD and increased secretion of BDNF could be neuroprotective.  The same drug tested being tested by Raptor for HD has been approved by the FDA for the treatment of a kidney disease called nephropathic cystinosis.

In the Raptor HD trial which took place in France, 96 patients with HD were randomized to treatment with RP103 or placebo. The objective of the study was to evaluate the effectiveness, safety and tolerability of RP103 in modifying Huntington's disease progression. RP103 appeared well-tolerated compared to the placebo group.  However, 6 patients in the RP103 arm of the study discontinued treatment, while just 1 patient in the placebo arm dropped out of the trial.  The primary efficacy endpoint of the study was the change from baseline in the Total Motor Score (TMS) sub-scale of the UHDRS at 18 months of treatment in the placebo and RP103 treated groups. Analysis of all 96 patients enrolled in the trial showed a positive trend towards slower progression of TMS in patients treated with RP103 vs. those patients on placebo, the primary endpoint of the study. TMS progression was 32% slower in patients treated with RP103 vs. those treated with placebo after 18 months treatment (however this effect was not statistically significant).

Since this is a 3 year study, patients were allowed to continue their baseline medication regime, including antidepressants and tetrabenazine.  Patients were not randomized in the study based on concomitant medications. To confirm that the TMS results were not influenced by a potential treatment effect of tetrabenazine on chorea (a sub-score of TMS) the subset of patients not receiving tetrabenazine were analyzed for TMS. In these 66 patients (32 under placebo and 34 under RP103), RP103 treatment caused a statistically significant 58% slower progression in TMS of 2.84 points compared to 6.78 points for placebo (p=0.03) at 18 months. Slower progression was seen across all TMS sub-score measurements including eye and hand movements, balance and gait, as well as maximal dystonia and maximal chorea. Adverse events were similar in the two groups and were comparable to what has been observed in other studies in this patient population.

For more information on the Raptor Pharmaceuticals go to www.raptorpharma.com

Stay tuned to www.hdsa.org for more information on the next steps for RP103 as a potential treatment for HD.