HD Insights™

H D I N S I G H T S HD Insights, Vol. 11 3 Copyright © Huntington Study Group 2015. All rights reserved. HD INSIGHTS: How did you become interested in orphan drug development? SASINOWSKI: I worked at the Food and Drug Administration (FDA) when Congress enacted the orphan drug law. I was asked to investigate how to make it work, because initially it wasn't working. My research led to the 1984 and 1985 amendments to the original 1983 law that made it as positive, constructive, and beneficial as it has proven to be. I drafted the original implementing regulations before I left the FDA in 1987. After that, I helped companies through the FDA pre-approval gauntlet for getting new orphan drugs to the market and patients in need. Due to my experience with the orphan drug law, I had a particular passion for helping with therapies for patients who are afflicted with rare conditions. I had also worked on developing the accelerated approval track for therapies for AIDS, because in the mid-1980s, the AIDS crisis was upon us. Fast Track is essentially a way to get drugs approved on the basis of a surrogate endpoint, where the ultimate clinical endpoint can be proven in a confirmatory post- approval trial. I helped Berlex Pharmaceuticals (now Bayer Healthcare Pharmaceuticals) with Betaseron (interferon beta-1b), the first therapy approved for multiple sclerosis. Betaseron was the first therapy ever approved by the FDA for a condition other than AIDS or cancer that relied upon this new system for accelerated approval. It was really ground-breaking, not only for patients with multiple sclerosis, but also as a trail blazer for other FDA regulatory precedents. HD INSIGHTS: How did you become interested in HD? SASINOWSKI: I have a long history of working with HD therapies. I was involved in the Care-HD study, the largest HD study that had yet been conducted. I was actually there 15 years ago when Drs. Karl Kieburtz and Ira Shoulson, professors at the University of Rochester and principle investigators for the study, broke the blind and announced the results. I represented VitaLine, one of the two companies that had therapies being investigated. VitaLine's Coenzyme Q10 (see HD Insights, Vol. 6) showed a 13% slower decline in the Total Function Capacity subscore of the Unified Huntington's Disease Rating Scale (UHDRS) compared to placebo. This was startling to the investigators, because a 13% between-group difference was by far the largest they had ever witnessed. More recently, I helped Prestwick Pharmaceuticals with getting FDA approval for tetrabenazine for treatment of chorea associated with HD (see HD Insights, Vol. 7). The company showed positive results in a single trial on its primary endpoint, and an effect on global impression, a secondary endpoint, but the FDA was also impressed with patients' stories. You will not find this talked about in the labeling for the product, nor if you scour the FDA medical reviews or statistical reviews. However, we found in our interactions with the FDA that they were impressed by anecdotal reports that some patients whose chorea was so severe that they needed help in feeding themselves were able to self-feed after treatment with tetrabenazine. This demonstrates that the FDA wants to see that a therapy is going to improve how a patient feels or functions on a daily basis, or survives. Also related to HD, I aided Avanir Pharmaceuticals with its dextromethorphan and quinidine (NUEDEXTA®) therapy for pseudobulbar affect, which was approved in 2010. Significantly, this was before the FDA Safety and Innovation Act (FDASIA) of July 8 th , 2012, which represents the first time in the history of our drug laws that the word "patient" appears. Our drug law started with the 1906 Pure Food and Drug Act, and one would think that in over a century of law-making, it would be impossible that the law would never mention patients, but it is true. Congress relied on the medical community and the regulators to decide what was best for patients. There was a shift in 2012, and Congress told the FDA—and in effect the medical and patient communities—that patients need to have a role in approval of new drugs. I have had about 10 meetings this year with the FDA division of neurology, and they want companies not just to rely upon measurements of physiological outcomes that have an unclear connection with a patient's daily life, but to discover how a new therapy affects how that patient is feeling on a daily basis, and how they are engaging in their activities of daily living. HD INSIGHTS: The Orphan Drug Act has been a great policy success. What are some of the remaining policy and regulatory challenges, especially as they might apply to HD? SASINOWSKI: A major initiative in the evolution of drug development is just now emerging: the engagement of the patient voice in all drug development issues. FDASIA mandated that FDA hold hearings to bring patients' voices into the regulatory process, and I think getting patients' voices into the conversation remains a challenge. The HD community has the Huntington's Disease Society of America, which was invited to be at that unveiling of the Care-HD study results 15 years ago. This is an example of how visionary people such as Drs. Kieburtz and Shoulson were already looking out for patient interests, but I think that kind of engagement has been slow in coming from the broader research community. We are on this cutting edge, and I predict that we will see more and more collaboration: for example, researchers and sponsors going out to patient groups as they plan trials to ask, "What do you think? What is important to you in your daily life?" H D I N S I G H T S (continued on Page 14...)

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