Dr. Cloyd earned his BS in pharmacy from Purdue University ('71), where he studied the biosynthesis of mitromycin by streptomyces verticillatus as a research assistant in medicinal chemistry. Following 2 years inpharmacy practice, he entered the combined PharmD/Hospital Pharmacy Residency Program at the University of Kentucky. His research project was the protein binding of phenytoin in newborns. Upon graduation in 1976, he accepted an appointment as an assistant professor in clinical pharmacy with the College of Pharmacy, University of Minnesota. From 1985–86, he completed a fellowship with Rene Levy, PhD at the University of Washington. His fellowship project dealt with the concentrations-dependence of carbamazepine auto-induction. In 2005, Dr. Cloyd established the Center for Orphan Drug Research for which he serves as director. The Center's mission is the development of orphan drugs for rare, pediatric neurological disorders. Today, Dr. Cloys is Professor and Lawrence C. Weaver Endowed Chair-Orphan Drug Development, Department of Experimental and Clinical Pharmacology College of Pharmacy, University of Minnesota.

Dr. Cloyd early academic career began with an emphasis on the clinical pharmacology of CNS drugs. He established a clinical practice in the Neurology Clinic at St. Ramsay Medical Center, where he managed antiepileptic drug therapy for patients with poorly controlled epilepsy; designed and taught a neurotherapeutics course in the College of Pharmacy; and established a research program in conjunction with the NIH-funded Comprehensive Epilepsy Program.

Dr. Cloyd's research program focuses on the pharmacology (basic and clinical) and development of orphan drugs for rare, pediatric neurological disorders. His research includes laboratory investigations of drug solubility, stability, and pharmacology; pharmacokinetic and efficacy studies in animals; drug safety, bioavailability and pharmacokinetic, pharmacogenomic, drug interaction, and efficacy studies in healthy volunteers and/or patients including children and the elderly. He holds 9 INDs and has served as principal or co-principal investigator for a number of Phase I-Phase III trials, many of which have supported NDA applications. He co-authored the orphan drug application for diazepam rectal gel (Diastat) and was a key leader in the successful development of product. The National Institutes of Health, the Food and Drug Administration, foundations, and the pharmaceutical industry have funded his research, which has led to100 papers in major medical and pharmacology journals as well as book chapters on various aspects of CNS drugs.

Dr. Cloyd has trained 23 PhD and post-doctoral fellows, many of whom have pursued a career in clinical pharmacology. He is actively involved in several international and national organizations including the International Conference on Rare Diseases and Orphan Drugs and the American Epilepsy Society, where he serves on the Board of Directors. In addition, he has served on an NINDS clinical trials study section and is a newly appointed member of the FDA Advisory Committee on Pharmaceutical Science and Clinical Pharmacology.

Dr. Lesko is the Senior Clinical Director of the Division of Pharmacy and the PGY1 Residency Program Director at Cincinnati Children's Hospital Medical Center. She is also Associate Professor of Clinical Pharmacy at the University of Cincinnati, James L. Winkle College of Pharmacy. Prior to joining the Division of Pharmacy at Cincinnati Children's Hospital Medical Center in 1989, Dr. Lesko was Assistant Professor of Clinical Pharmacy at the St. Louis College of Pharmacy and maintained a clinical practice at the St. Louis Children's Hospital. Dr. Lesko received her Bachelor of Science in Pharmacy degree from the St. Louis College of Pharmacy and her Doctor of Pharmacy degree from Northeastern University. She completed her residency training at Tufts Medical Center and Boston Floating Children's Hospital.

As part of the pharmacy leadership team at Cincinnati Children's Hospital Medical Center, Dr. Lesko has played an active role in the development and expansion of the pharmacy's clinical services. Those services currently include seven decentralized pharmacists, nineteen clinical specialists and a clinical coordinator that practice in a variety of critical care, acute care and ambulatory settings. She established an ASHP accredited residency program in 1992 and serves as the residency program director. Dr. Lesko is the Vice Chair of the Pharmacy and Therapeutics Committee and co-leads the hospital's adverse drug event reduction initiative. She has also led a pediatric adverse drug event reduction initiative for a national healthcare system.

Dr. Lesko has served as President of the Pediatric Pharmacy Advocacy Group (PPAG), as a member of the PPAG Board of Directors and as a member of the PPAG Advisory Board. She has served as a member of the Commission on Credentialing for the American Society of Health-System Pharmacists (ASHP) and is a guest surveyor.

“Anne served as President at perhaps our most vulnerable time in our organizations history, and through good decision making, backbone, and hard work, got us through a very difficult time financially. Without Anne and her substantive leadership skills, I think there is a good chance there would not be a PPAG today,” said Dr. Richard Helms, Chair of the Helms Selection Committee, “In addition, she has been instrumental to the evolution of medication safety in children, and to post-doctoral training in pediatric pharmacy. She has been a thoughtful and consistent voice for improved medication use in children, for the unique health system challenges in treating children, and for effective care solutions.”

Established in 2006, the Richard A. Helms Award of Excellence in Pediatric Pharmacy Practice recognizes (1) sustained and meritorious contributions to PPAG and to pediatric pharmacy practice, and (2) contributions of importance to education, new knowledge, and outreach. The Richard A. Helms award is made possible by the generous donations of colleagues, friends, and past postdoctoral trainees of Dr. Helms.

The Helms Award Presentation and Lecture will be given during the 24th Annual PPAG Meeting on May 1, 2015 at the Minneapolis Marriott City Center in Minneapolis, Minnesota.

On March 10, 2015, the U. S. Food and Drug Administration (FDA) approved dinutuximab (Unituxin, United Therapeutics Corporation), in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Unituxin is a disialoganglioside, GD2-binding chimeric monoclonal antibody (mAb) that binds cell surface GD2 and induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The recommended dose of Unituxin is 17.5 mg/m2/day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles. Cycles 1, 3, 5 are 24 days in duration and cycles 2 and 4 are 32 days in duration. Verification of adequate hematologic, respiratory, hepatic, and renal function is required prior to initiation of each Unituxin course and premedication with analgesics, antihistamines, antipyretics combined with hydration is required prior to initiation of each Unituxin infusion.

The approval was based on a significantly improved event free survival (EFS) in 113 patients with high-risk neuroblastoma. Patients were 11 months to 15 years of age (median age 3.8 years). The number of EFS events (%) was 33 (29%) for the Unituxin and 13-cis-retinoic acid (RA) arm and 50 (44%) for RA alone [hazard ratio for EFS (years): 0.57; 95% CI: 0.37 to 0.89; p=0.01]. The most common adverse reactions (ARs) observed in Unituxin/RA-treated patients were primarily gastrointestinal, hematologic, electrolyte, hepatic and infusion reaction related. A detailed list can be found in the prescribing information linked below. Across clinical studies, 17% of patients tested positive for anti-dinutuximab binding antibodies. Neutralizing antibodies were detected in 3.6% of these patients.

The mean (range) terminal half-live of dinutuximab is estimated to be 10 (6 to 33) days based on a population pharmacokinetic analysis of a clinical study where Unituxin was administered in combination with RA in 27 children with high-risk neuroblastoma [age (mean±SD): 3.9±1.9 years]. Dinutuximab clearance increased with body size. No formal pharmacokinetic studies were conducted in patients with renal or hepatic impairment. Dinutuximab is not expected to have enzyme- or transporter-based drug-drug interactions.

Full prescribing information is available at http://go.usa.gov/3aGzP. The Office of Clinical Pharmacology (OCP) regulatory reviews for new drugs or biologics are often available for viewing shortly following approval at the Agency's Drugs@FDA website (http://go.usa.gov/3aGzz).

We always welcome your thoughts regarding the format, content, and utility of information you receive via this Burst email initiative. Comments may be sent via email to ocp@fda.hhs.gov.

This burst was prepared by the Clinical Pharmacology Review Team including Jingyu (Jerry) Yu, Ph.D., Clinical Pharmacology and Pharmacometrics Reviewer; Liang Zhao, Ph.D., Team Leader, Division of Pharmacometrics; and Hong Zhao, Ph.D., Team Leader, Division of Clinical Pharmacology V, Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.