HD Insights™

HD INSIGHTS: How did you first become interested in HD? CLARENCE-SMITH: I read a Victorian novel when I was nine years old, the diary of somebody who knew that one of his parents had a disease that he would also have. The book ends with, "This is where I stop; I now have the shakes." I thought it was a horrible disease, since you knew exactly what was going to happen to you, and then it happened. And of course, as I read the diary as a child, I kept hoping that it would turn out that he didn't have the un-named disease. Much later, when I studied medicine, I realized that the disease I had read about in my childhood must have been HD. When I was 20, I knew a family who had HD, and was again confronted with the sadness and concerns about the children faced by families affected by this disease. I had absolute faith that biochemistry could find a drug that would stop or slow the disease. HD INSIGHTS: As founder and CEO of Prestwick Pharmaceuticals, you were instrumental in bringing tetrabenazine to market in the United States. Did you ever think that your interest in finding a biochemical treatment for HD would lead to an approved drug? CLARENCE-SMITH: No, I never thought of that in those days. I just knew that I wanted to find a cure, and I kept hoping that I would either read something in the literature which would point to the cure, or that I would be able to do real research into finding the cure. Dr. Kathleen Clarence-Smith has dedicated her career to developing novel pharmaceuticals and bringing them to market. As the founder and CEO of Prestwick Pharmaceuticals, she helped bring tetrabenazine, the first FDA approved treatment for HD, to the US. She has held senior positions in major pharmaceutical companies (Roche, Sanofi, and Otsuka) and authored over 100 peer-reviewed publications. Dr. Clarence-Smith discussed the history and future of HD therapies with HD Insights. The following is an edited transcript of the conversation. HD INSIGHTS: How did you become interested in tetrabenazine? CLARENCE-SMITH: I met Dr. Joseph Jankovic at a meeting, and he knew that I was working on trying to get drugs approved by the FDA. He wanted more than anything to see tetrabenazine approved in this country. I called the company who manufactured tetrabenazine in Europe and managed to convince them that it was possible to get this drug approved in the United States, and I was able to raise money to do it. HD INSIGHTS: What are the current limitations of tetrabenazine? CLARENCE-SMITH: It seems to only treat chorea, and clearly we also need treatments for the cognitive impairment and behavioral symptoms seen in HD. It remains to be seen whether we need three different treatments, or one yet-to-be-discovered therapy for all the disease symptoms. A lot more work needs to be done to understand the physiopathology of the cognitive impairment. For behavioral symptoms, I think that tetrabenazine has not been completely studied. I would have expected that a drug such as tetrabenazine that acts on the dopamine axis would also improve behavioral symptoms. Today, I'm leaning towards a need for three treatments, but sometimes you get surprised in drug discovery and development. (continued on Page 3...) VITAL SIGNS NAME: Kathleen (Kitty) Clarence-Smith, MD, PhD CURRENT POSITION: Chairman of the Board of Chase Pharmaceuticals; Partner, KM Pharmaceuticals Consulting (clients include Lundbeck). EDUCATION: MD and PhD in Neurosciences, Université de Tours, France; Residency in Neurology, Salpêtrière, Paris, France; post-doctoral fellowship at Johns Hopkins University School of Medicine, Department of Pharmacology and Experimental Therapeutics. HOBBIES: Reading, currently Walter Isaacson's Steve Jobs. Dr. Kathleen Clarence-Smith Meet the Investigator "I just knew that I wanted to find a cure" Copyright © Huntington Study Group 2014. All rights reserved. H D I N S I G H T S HD Insights, Vol. 7 2

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