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New network will advance treatments for children

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Three leaders from Children’s National Health System are among the investigators of a new FDA-funded program created to launch a global clinical trials network. The initial $1 million grant from the Food and Drug Administration (FDA) establishes a network among the Institute for Advanced Clinical Trials for Children (I-ACT for Children), the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) (affiliated with Children’s National), PEDSnet, the James M. Anderson Center for Health Systems Excellence and the Critical Path Institute, to address the unmet medical needs of children by improving quality and efficiency in developing innovative pediatric drugs and devices.

Along with the fiscal 2017 funds, there is a potential for $1 million in funding each year for an additional four years to I-ACT for Children, contingent on annual appropriations and the availability of funding. I-ACT for Children is a new independent, nonprofit organization that works to improve the planning and completion of pediatric clinical trials. PEDSnet and the Anderson Center will serve as the network’s data and learning core, while the Critical Path Institute will serve as the regulatory science core and NCC-PDI will serve as the medical device core.

From Children’s National, the investigators include: Peter Kim, M.D., Ph.D., vice president of the Sheikh Zayed Institute for Pediatric Surgical Innovation; Kolaleh Eskandanian, Ph.D., executive director of the Sheikh Zayed Institute and NCC-PDI and Johannes van den Anker, M.D., Ph.D., division chief of Clinical Pharmacology and vice chair of Experimental Therapeutics.

“We are pleased that this grant addresses innovative reengineering of the pediatric device trials system,” says Eskandanian. “In contrast with drug trials, device trials are generally less optimally understood in academic medical centers and clinical sites.”

She explains that children have medical device needs that are considerably different from adults. Designing devices for children requires considerations such as growth and development, anatomical and physiological differences. Often, the lack of available devices for children forces clinicians to use an adult device off-label or to improvise. Off-label use may be the only option, but such use can bring risks of serious adverse events that could be avoided if there were more FDA–approved pediatric devices.

“Thanks to partnership with I-ACT we will be able to address the pressing need to improve clinical trials and post-market monitoring of pediatric devices,” says Eskandanian.

Leading the network as principal investigator is Edward Connor, M.D., president of I-ACT for Children and an emeritus professor of Pediatrics, Microbiology, Immunology, and Tropical Medicine at George Washington University School of Medicine and Children’s National.

Work has been initiated to integrate network components and engage public and private shareholders. Next steps include selecting priority projects for implementation in 2018 and beyond, and scaling the network in North America and abroad.

Funding for this work was made possible, in part, by the Food and Drug Administration through grant 1 U18 FD 006297. Views expressed in written materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

Children’s National Chief of Allergy and Immunology helps move gene therapy forward

Catherine Bollard

Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology, recently shared her expertise on an FDA panel that unanimously expressed its support for a pediatric cancer T-cell therapy called CTL019.

On July 12, 2017, a U.S. Food and Drug Administration advisory committee unanimously expressed its support for CTL019 – a pediatric cancer T-cell therapy. If the FDA follows the advice from the 10-member Oncologic Drug Advisory Committee (ODAC) – which included Children’s National Health System’s Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology and Director of the Program for Cell Enhancement and Technologies for Immunotherapy – CTL019 will become the first gene therapy to hit the market.

“Many of these children with recurrent cancer are out of other options to treat their illness,” said Dr. Bollard. “We are encouraged by these findings and the potential for this therapy to improve outcomes and quality of life.”

CTL019 is a chimeric antigen receptor (CAR) T-cell therapy, comprised of genetically modified T cells that target CD19, an antigen expressed on the surface of B cells. Also known as tisagenlecleucel, the therapy targets a single type of cancer called acute lymphoblastic leukemia and was created by Novartis.

In clinical trials, CTL019 showed unparalleled effectiveness. Of the 68 patients who received the drug, 52 responded almost immediately, and their cancer disappeared within the first three months. Seventy-five percent of those patients remained cancer-free six months after treatment. The therapy has one main side effect: an immune reaction called cytokine release syndrome, which can be deadly, with extended spiking fevers and other symptoms.

However, because of CTL019’s high efficacy, FDA scientists asked the ODAC panel to focus on the therapy’s safety and manufacturing challenges rather than whether or not it works.

Several committee members, including Dr. Bollard, expressed apprehension about the T-cell subpopulations’ heterogeneity, which could affect safety and efficacy. Another issue for consideration by the ODAC panel was the long-term side effects of CTL019 and the possibility that the T-cell modification could go awry, causing secondary cancers in the future.

Despite these concerns, the committee concluded that the strong efficacy data and the near-term benefits of CAR-T therapy more than tipped the scales in favor of the therapy. ODAC members were also pleased with Novartis’ plan to minimize risk, which includes limiting CTL019 distribution to selected centers with CAR T-cell therapy experience, and extensive, long-term post-marketing surveillance plans.

The FDA is not required to follow the ODAC panel’s advice when making its final decision, but it often does so. A final decision by the FDA is anticipated by late September.

Read more about the story in the Philadelphia Inquirer, Medpage Today and Healio.com.