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Experts to explore drugs’ potential to delay type 1 diabetes


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3 minutes

Stephen E. Gitelman, MD
Stephen E. Gitelman, MD

Efforts to delay the onset of type 1 diabetes have been re-invigorated by success from a stage 2 prevention trial with teplizumab showing a three-year median delay in the onset of stage 3 type 1 diabetes.

Panelists will discuss this progress in The Quest to Delay or Prevent Type 1 Diabetes Onset — Recent Interventional Trials on Friday, June 23, at 3:45 p.m. PT in Room 28 of the San Diego Convention Center. This session also will be available via livestream for registered meeting participants.

In November 2022, the U.S. Food and Drug Administration (FDA) approved teplizumab for use in diabetes prevention, the first disease-modifying therapy in type 1 diabetes. The two-week infusion was shown to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who have stage 2 disease.

“In the type 1 diabetes community, we are trying to build on the observations seen with teplizumab and the success of its study,” said Stephen E. Gitelman, MD, Director of the Pediatric Diabetes Program at the University of California, San Francisco. “We want to know: Are there other drugs that can interdict this process besides teplizumab? And can we intervene at an earlier stage and show similar or better efficacy?”

Dr. Gitelman will provide an overview of previous attempts to delay the onset of type 1 diabetes. He will be joined by William E. Russell, MD, the Cornelius Vanderbilt Chair and Professor of Pediatrics, Pediatric Endocrinology at Vanderbilt University Medical Center, who will discuss the use of abatacept in the prevention of type 1 diabetes.

Abatacept is a selective costimulatory modulator that blocks T-cell activation by CD28 binding to CD80 and CD86 on antigen-presenting cells and also affects T follicular helper cells and T peripheral helper CD4-positive T-cells.

“What is intriguing about abatacept is that it was used in a study of stage 3, new-onset disease in a Type 1 Diabetes TrialNet study and was found to safely and effectively extend the honeymoon stage,” Dr. Gitelman said

Dr. Russell and his colleagues recently published results of a phase 2 randomized, placebo-controlled trial testing abatacept for delaying type 1 diabetes in stage 1 relatives at risk for type 1 diabetes. Twelve months of treatment changed immune cells and improved C-peptide, but it did not meet pre-set criteria for the delay of stage 2 diabetes individuals at stage 1.

Ingrid Libman, MD, PhD, MPH, Associate Professor in the Division of Endocrinology and Director of the Diabetes Program at UPMC Children’s Hospital of Pittsburgh, will discuss another promising agent being explored for the delay or prevention of type 1 diabetes: hydroxychloroquine.

More commonly known as an antimalarial drug, hydroxychloroquine has also been used in the treatment of rheumatoid arthritis and lupus. The agent is thought to work by interfering with lysosomal activity and autophagy, interacting with membrane stability, and altering signaling pathways and transcriptional activity, with multiple subsequent effects that may interdict autoimmune-mediated destruction of beta cells.

A phase 2 study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that compared hydroxychloroquine with placebo in people at risk for type 1 diabetes was completed in November 2022 and results will be presented at this session.

“We are taking advantage of what we know about immune responses from prior studies and trying to repurpose these two drugs,” Dr. Gitelman said.

Carla Greenbaum, MD, Director, Benaroya Research Institute Diabetes Program, and Vice-Chair of Type 1 Diabetes TrialNet, will reflect on past progress and future opportunities and challenges in the field.

“The outcomes of these large trials in stage 1 disease will be important to anyone in the type 1 diabetes community,” Dr. Gitelman said. “Now that we have a pretty good crystal ball to predict who might get type 1 diabetes, we want to build on the teplizumab study findings and find safe and effective treatments to delay or prevent it from occurring.”