Teplizumab Delays Onset of Type 1 Diabetes
The US Food and Drug Administration (FDA) recently approved the use of a new drug Teplizumab, an immunotherapy drug which has been shown to significantly delay the onset of type 1 diabetes. The approval marks the first potential disease modifying therapy for patients with type 1 diabetes in the United States, for whom there had been no approved treatment other than a lifetime of intravenous insulin infusion.
The FDA’s approval of Teplizumab on November 17, 2022, under the brand name Tzield, was largely made possible by researchers from the UCSF Diabetes Center. The drug can delay the onset of type 1 diabetes by at least two years.
“This is a landmark achievement, and our diabetologists and basic scientists at UCSF were instrumental in the discovery, validation, and clinical demonstration of Teplizumab,” said Mark S. Anderson, MD, PhD, the Robert B. Friend and Michelle M. Friend Endowed Chair in Diabetes Research and director of the UCSF Diabetes Center. “Until now, the only real therapy for patients has been a lifetime of insulin replacement. This new therapy targets and helps to halt the autoimmune process that leads to the loss of insulin.”
The approval of Teplizumab, an anti-CD3 monoclonal antibody, has special significance for UC San Francisco. Renowned immunologist Jeff Bluestone, PhD, the UCSF A.W. and Mary Margaret Clausen Distinguished Professor of Endocrinology and Metabolism emeritus and chief executive officer and president of Sonoma Biotherapeutics, was instrumental in developing the monoclonal antibody.
“It’s been a long journey in developing Teplizumab, starting 36, 37 years ago,” said Bluestone. “Our first major publication was in 2002 in the New England Journal of Medicine, where we showed we could take patients who had just developed type 1 diabetes and try to prevent or reverse the disease before all the islets were destroyed, and so that was really the first demonstration that Teplizumab could slow down, if not reverse, the disease in many of these patients.”
UCSF’s TrialNet team – including Anderson and UCSF pediatric endocrinologist Stephen Gitelman, MD, – played a critical role in nationwide clinical trials to discover ways to delay and prevent type 1 diabetes. The pivotal trial that led to FDA approval showed that a single 14-day dose of Teplizumab delayed the onset of type 1 diabetes in children and adults by an average of two years in pre-symptomatic patients.
“UCSF has been an important part of various clinical networks trying to solve the problem of type 1 diabetes,” says Gitelman, the Mary B. Olney, MD / KAK Distinguished Professor in Pediatric Diabetes and Clinical Research and director of UCSF's pediatric diabetes program. “The results of the Teplizumab trial were very dramatic in delaying the progression of type 1. We have conducted a number of other prevention trials over the past few decades – this is the first one that’s worked.”
Type 1 diabetes results from immune destruction of a single cell type – the insulin-producing beta cell. With the loss of that one cell type, the pancreas does not make insulin which helps blood sugar enter the body’s cells for use as energy. Without insulin, blood sugar cannot get into cells and builds up in the bloodstream. High blood sugar causes many of the symptoms and complications of diabetes, making it very a difficult chronic illness to manage. Type 1 diabetes usually develops in children and teens, but it can happen at any age.
“Over the years we’ve had a number of patients and families that have come through that have received this experimental medication here,” says Gitelman. “There’s been a lot of excitement with each of these efforts the way it’s altered the natural course of diabetes over time.”
With the approval of Teplizumab, the diabetes team at UCSF will begin infusions for patients who are for the moment individuals with preclinical type diabetes (>2 autoantibodies and glucose intolerance (Stage 2)). The center’s clinical researchers are also continuing to champion the next generation of therapies for type 1 diabetes that target the immune system, including research into regulatory T cells which may have a pivotal role in treating prediabetic conditions.
The UCSF Diabetes Center is an integrated team of researchers and physicians in fields of cell development, metabolism, and immunology, internationally renowned for excellent patient care, cutting-edge science, and lifesaving patient education in both Type 1 and Type 2 Diabetes. Based at Parnassus on two floors in Health Sciences West, there are also have labs at The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and Medical Sciences, with affiliate faculty spanning from to Mission Bay, Gladstone Institute, to Zuckerberg San Francisco General Hospital and Trauma Center.