HD Insights™

H D I N S I G H T S Reilmann, cont... HD INSIGHTS: You are involved in a number of HD clinical trials. Which do you find most promising? REILMANN: I think a couple of promising compounds are around the corner. The HD field has attracted a lot of recent attention from different sponsors. Pridopidine has shown a potential benefit for motor disability in HD3. The drug has a very benign safety profile, so we are currently planning to start a new trial involving 50 centers and around 400 participants in North America, Europe and Australia, which will increase the dose of the drug compared to previous trials. Unfortunately, this is necessary because the first two trials were formally negative, as the primary endpoint did not reach its predefined significance level. But, it is nice to see this drug get another chance, because currently, we only have drugs available for lowering the amount of involuntary movements. Pridopidine would fill a gap that we have not been able to address in a positive way. We have other compounds for which we expect clinical trial results sometime soon. There's the exploration of slow-release forms of tetrabenazine, which may create additional benefit to patients and lower potential side effects. And there are a number of other compounds currently being considered for symptom relief, such as PDE10A inhibitors (see HD Insights, Vol. 5). Then there is the buproprion trial in Europe, which is trying to address the problem of apathy in HD. And of course we are expecting the results of the large HSG trials with CoQ10, which will be interesting to hear. We have other sponsors looking into microglial activation patterns that could potentially be ameliorated, and we could also potentially have treatment trials with sRNA addressing the lowering of mutant huntingtin in HD patients. This was the target of a trial with Selisistat for which I was the PI with Siena Biotech, the results of which will soon be available. We will have to see which of these approaches will contribute to our long-term aim to actually change the disease progression of HD. HD INSIGHTS: Dr. Reilmann, thank you for your time, and for your continuing dedication to HD care and research. 1 Tabrizi SJ, Reilmann R, Roos RA, et al. Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: analysis of 24 month observational data. Lancet Neurol. 2012 Jan;11(1):42-53. 2 Biglan KM, Zhang Y, Long JD, et al. Refining the diagnosis of 3 Reilmann R. The pridopidine paradox in Huntington's Huntington disease: the PREDICT-HD study. Front Aging Neurosci. 2013 Apr 2;5:12. disease. Mov Disord. 2013 Sep;28(10):1321-4. doi: 10.1002/mds. 25559. Epub 2013 Jul 11. PubMed PMID: 23847099. HD InsightsTM and the Huntington Study Group would like to thank Auspex for their support of HSG 2013. HD Insights, Vol. 6 Copyright © Huntington Study Group 2013. All rights reserved. 3

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