"Dose as a Surrogate-A Clinician's Journey to Enlightenment (or How I got Exposed to Exposure)"
Monday, October 21, 2013
2:00 p.m.-3:00 p.m.
FDA WO Campus, Bldg. 51, Room 1300
Seminar by Dr. Diane Jorkasky
CMO of Complexa Therapeutics
Dr. Diane Jorkasky is a highly regarded medical scientist and researcher in the pharmaceutical industry with a broad background across research and all phases of clinical development and in every therapeutic area. She is CMO of Complexa Therapeutics, which has developed nitro-fatty acid signaling technology for treatment of inflammatory diseases. She sits on the Board of Directors of Tengion Inc, a regenerative medicine company, and Q Therapeutics, a CNS regenerative medicine company, the Scientific Advisory Board of BioMotiv, and is President of her own research and development consulting business with emphasis on translational pharmacology and medicine in the development of drugs. Her clients include venture firms, academia, pharma, and biotechnology companies.
Her broad experience includes positions as Head of Development and Chief Medical Officer at Endo pharmaceuticals, with involvement in the development of drugs, devices and generics, and Aileron Therapeutics in Cambridge, Massachusetts, where she guided the research and development of stapled peptides for clinical indications. Prior to these appointments she had been Vice President of Global Clinical Research Operations, its clinical research units and leader of the Operational Excellence Board for Development at the Pfizer Global Research and Development New London, Connecticut. In this role Dr. Jorkasky was responsible for ensuring that all exploratory development, clinical pharmacology (phase 1-4), translational medicine and clinical technology studies were appropriately conducted. She led the complete alignment of the three Pfizer Clinical Research Units, located in the US, Europe and Asia, which led to being awarded certification by American Accreditation for Human Rights Protection Policies for their clinical research process, the first in industry to achieve such a recognition. In her role as leader of the Operation Excellence Board for Development, she drove data standards and improvements in Pfizers drug development process to gain efficiencies in timelines and performance from Phase 1 to 4. Prior to that, Dr Jorkasky had been vice president of Clinical Pharmacology at SmithKline Beecham, chief of the renal division at Presbyterian Medical Center and faculty member at Penn where she had received her medical degree.
Dr Jorkasky is a member of the Connecticut Academy of Science and Technology. She has been recognized by the Connecticut Womens Hall of Fame for her scientific leadership and mentoring of young women and the Connecticut Council on Technology for her leadership in driving the creative technological advances in Pfizers clinical research units. Dr. Jorkasky is board certified in internal medicine, nephrology and clinical pharmacology. She is on the faculties of UCSF, Yale, Penn and Uniformed Service of Health Sciences Medical Schools. She has published on over 100 peer review articles. Recently Dr. Jorkasky was selected to be a Woodrow Wilson visiting fellow. In 2011 she was recognized by Whos Who as Professional of the Year representing pharmaceuticals and biotechnology. The College of Wooster, where she obtained her undergraduate degree in chemistry, has honored her with the Distinguished Graduate award in 2013.
Both the industry and regulatory agencies seem to be totally whetted to the concept of dose, and generally ignore or subordinate the actual pharmacokinetic exposure data, exclusively focusing on the dose. Yet, at any given dose, what the patient actually receives in terms of drug in blood and at the site of action may vary widely even at the dose. Regulatory agencies are reluctant to rely on biomarkers of drug activity, insisting appropriately on having demonstration of clinically meaningful benefit. Yet, that logic appears to be lacking when dealing with dose vs. exposure. The thesis of this presentation is that dose is a biomarker, and that the clinically, biologically, and pharmacologically meaningful indicator is the exposure. If the drug does not achieve appropriate concentrations at its site of action, which is related to the exposure in the blood that is sampled, how does the drug then work? The dose is irrelevant! Nonetheless, the simple concept of exposure being the important element, moreso than dose, evades regulatory guidance documents (consider the guidance of the selection of doses for first in human studies) and regulatory-sponsor interactions in many cases, and seems to be highly dependent on who is doing the review. For clinical pharmacologists both in the Agency and in industry, this is an anathema. But it is not surprising since the lexicon of exposure response relationships tends to be very jargonistic, and then there are those equations!! This seminar is the presenters road to enlightenment on the concept of exposure. However, she takes a hard look at why the use of exposure instead of dose is religiously held steadfast by some, why the FDA has not been consistent across divisions in its application to regulatory reviews, why sponsors are equally erratic in considering exposures rather than dose alone, and why all of these behaviors are to the total detriment to the medical treatment of patients.