Two Penn researchers selected as recipients of prestigious Clinical Research Achievement Award

Two researchers from the Perelman School of Medicine at the University of Pennsylvania and the Penn Cardiovascular Institute (CVI) are among the 2014 recipients of the prestigious Clinical Research Achievement Award for their work in cardiovascular science. The awards are presented by the Clinical Research Forum to physician scientists from across the country. Ten projects are selected annually that represent outstanding examples of research projects that benefit the health and wellbeing of the general public. This is the first time that one academic institution has had two recipients honored in one year.

"Clinical research culminates years of basic and translational science to bring new treatments to patients, and I'm always excited to see the groundbreaking clinical research recognized every year by the Clinical Research Forum," said National Institutes of Health (NIH) Director Francis S. Collins, MD, PhD. "This is just the tip of the iceberg of the incredible work coming out in the field, much of it funded by the NIH."

Stephen E. Kimmel, MD, MSCE, professor of Medicine and Epidemiology, received the award for research that determined that a gene-based method for selecting patients' doses of the popular heart medication warfarin is no better than standardized dosing methods. Warfarin is a blood thinner used to prevent clots. It is generally considered to be a very effective medication, but dosing must be properly adjusted for each patient, who then must be closely monitored for complications.

Approximately 2 million Americans, primarily older patients, take warfarin to keep blood from excessive clotting, or coagulation. Currently, doctors face major challenges in determining the right dose of warfarin for each patient because individuals vary widely in how quickly their bodies' break down and respond to the drug. Taking too much warfarin could result in bleeding problems and taking too little warfarin will not stop clots from forming. Doctors believed that one possible way to improve the dosing of patients on warfarin is to incorporate genetic information when selecting their initial dose.

The Clarification of Optimal Anticoagulation through Genetics (COAG) trial, led by Dr. Kimmel, was a clinical trial comparing two strategies to dosing warfarin: a pharmacogenetic dosing strategy (that used both clinical plus genetic information) and a clinical-only dosing strategy (that used the same clinical information but did not use genetics). The COAG trial demonstrated that, overall, the gene-based method for selecting patients' doses of warfarin was no better than a standardized dosing method. Specifically, the addition of genetics to clinical information did not improve the level of blood thinning. In fact, the addition of genetics to clinical information made the level of blood thinning less stable in African Americans.

Daniel J. Rader, MD, chief, Division of Translational Medicine and Human Genetics, received the award for research that developed the first effective pharmacologic intervention, lomitapide, for the rare and deadly cholesterol disorder, homozygous familial hypercholesterolemia (hoFH). HoFH is a genetic disorder caused by mutations in both alleles of the LDL receptor leading to markedly defective clearance of LDL cholesterol from the blood. It is characterized by cholesterol levels of greater than 500 mg/dL and markedly premature atherosclerotic cardiovascular disease in childhood. Standard cholesterol-lowering therapies such as statins are ineffective in treating this disease and prior to the development of lomitapide, the standard of care had been LDL apheresis, a system of regular purging of the blood of cholesterol which is laborious and not widely available.

Dr. Rader and colleagues at Penn worked for over a decade to reach the pivotal safety study of lomitapide that led directly to FDA and European approval of the medication for the treatment of hoFH. Early reports from patients indicate that lomitapide is allowing patients to reduce their LDL-C levels substantially, and in some cases to reduce or discontinue LDL apheresis. Lomitapide represents the first effective pharmacologic therapy for this devastating and fatal disease. Its successful development was a remarkable collaboration between academia, foundation, government, big pharma, and small biotech. Its availability has energized the worldwide community of hoFH patients and their physicians and provided new hope for patients with this disease.

"These two studies are excellent examples of how properly designed and executed clinical trials advance medical care," said Michael S. Parmacek, MD , chair, Department of Medicine and founding director of the Penn CVI. "The work by Dr. Kimmel highlights the importance of evaluating new technologies before they are commercially distributed. The study by Dr. Rader will transform the lives of children and young adults who present with hoFH. Together, these studies build upon Penn's long tradition as pioneers in scientific discoveries and medical breakthroughs in heart and vascular care."

The Clinical Research Forum is an organization comprised of the nation's most prestigious and acclaimed academic medical centers and healthcare systems whose goal is to sustain and expand a cadre of talented, well-trained clinical investigators at all stage of career development, and support nurturing environments and comprehensive research capabilities within academic institutions. Its mission is to provide leadership to the national clinical and translational research enterprise and promote understanding and support for clinical research and its impact on health.