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Researchers to Test Innovative Gene Therapy in Hemophilia-A Clinical Trial

Milwaukee, June 16, 2020 – Patients are now able to participate in a phase I, first-in-human FDA approved clinical trial seeking a potential long-term treatment for Severe Hemophilia A, using a gene therapy that targets synthesis of coagulation Factor Eight (FVIII), which is stored and released from blood platelets at the site of an injured blood vessel. This novel approach of targeting therapeutic agents to platelets was first developed at the Medical College of Wisconsin (MCW) by David A. Wilcox, PhD, associate professor of pediatrics within the division of Hematology, Oncology, and Blood Marrow Transplant. The study will recruit five patients from all over the country for treatment at Froedtert & MCW.

Hemophilia A is an X-linked inherited bleeding disorder, occurring in approximately 1 in 10,000 males, caused by a molecular defective resulting in a deficiency of a blood clotting protein, FVIII. There are about 20,000 Hemophilia A patients in the United States and 400,000 worldwide. About 30 percent of patients that are currently treated with replacement FVIII to restore blood clotting may develop clinically relevant immune responses to the transfused FVIII product, rendering the treatment ineffective. Estimates suggest more than 6,000 patients in the United States alone develop inhibitors to FVIII each year.

Dr. Wilcox’s novel approach uses a lentiviral vector-based gene therapy, Pleightlet™, that modifies bone marrow stem cells to drive synthesis of a normal FVIII replacement gene leading to storage specifically within the patient’s platelets. The platelets would then act as the FVIII carrier and delivery vehicle within the body to stop uncontrolled bleeding.

“This treatment approach is expected to avoid exposure of FVIII to the patient’s immune system by hiding FVIII within blood platelets until released directly at injured blood vessels, thus restoring normal clotting activity even in patients with immune reactions to FVIII,” said Dr. Wilcox. “Not only does it allow us to provide care to patients who previously were difficult to be treated due to complications they experienced from replacement FVIII, but also because it enables the patient’s own body to produce normal FVIII protein.”

The clinical trial will receive approximately $1.6 million in funding from the National Institutes of Health National Heart, Lung and Blood Institute this year ($8.2 million over five years) to treat patients with severe hemophilia A with inhibitors. This trial is a collaborative effort with co principal investigators Dr. Wilcox; Parameswaran Hari, MD, Armand J. Quick/William F. Stapp Professor of Hematology at MCW; Shawn Jobe, MD, PhD, hematologist at the Versiti Blood Center of Wisconsin. Additional co-investigators include: Bryon D. Johnson, PhD, professor of pediatrics and microbiology & immunology at MCW; Qizhen Shi, Qizhen Shi MD, PhD, professor of pediatrics at MCW and senior investigator at the Versiti Blood Center of Wisconsin Blood Research Institute; Ruta Brazauskas, PhD, associate professor of biostatistics at MCW; Myriam A. Armant, PhD, instructor in pediatrics at the Immune Disease Institute at Boston Children’s Hospital, and Frederic D. Bushman, PhD, William Maul Measey Professor in Microbiology at the University of Pennsylvania. The corporate sponsors of the study are Sirion Biotech and Platelet Targeted Therapeutics.

“We believe this could be a potential long-term treatment for Hemophilia A, and success of this gene therapy research could lead to significantly improved disease management for people who make antibodies following infusion of conventional FVIII products,” Dr. Wilcox said.

Early studies at MCW and the Versiti Blood Center of Wisconsin’s Blood Research Institute in 2003 and 2006 by Dr. Wilcox, Dr. Shi and Robert R. Montgomery, MD, clinical professor of pediatrics at MCW, formed the foundation of this work. In 2013 Dr. Wilcox’s lab showed platelet FVIII improved hemostasis in large animals with hemophilia A. While only adult Hemophilia A patients with inhibitory antibodies to FVIII may participate in the current proposed trial of this investigative drug, depending on the results, adults without inhibitors and children may also eventually be eligible to participate in later phases.

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