Teplizumab (Tzield®) helps preserve the ability of children and adolescents with new-onset type 1 diabetes to make their own insulin, a phase 3 trial finds. The drug was approved by the U.S. Food and Drug Administration (FDA) in November 2022 after it was shown to delay the onset of stage 3 type 1 diabetes.
Now, the PROTECT study has evaluated whether it could also preserve the function of beta cells—which produce insulin—in recently diagnosed youth. The randomized phase 3 trial found that teplizumab did achieve this, but that trial also suggested that there was improvement in other clinical parameters including reduced reliance on insulin medications, higher grade hypoglycemia, time in range of glucose, and quality of life. The researchers published their findings in the New England Journal of Medicine on October 18.
“There has been nothing available to stop the progression of type 1 diabetes after the diagnosis,” says Kevan Herold, MD, C.N.H. Long Professor of Immunobiology and chair of TrialNet, an NIH-sponsored consortium focused on delaying and preventing the disease. “We know that kids with new-onset diabetes lose the ability to make insulin over a period of years. Teplizumab seems to slow that down.”
Teplizumab preserves function of beta cells among other benefits
The PROTECT study was a randomized, placebo-controlled trial that enrolled children and adolescents with type 1 diabetes who had received a diagnosis of type 1 diabetes within the previous six weeks. All participants initially underwent a screening process that evaluated beta cell function. Following the screening, selected participants either received a 12-day course of intravenous teplizumab or a placebo. Then, six months later, participants received a second 12-day course. However, because of the COVID-19 pandemic, a small fraction of participants received the second course a year after the initial dose.
After 18 months, the researchers assessed changes in beta cell function. They also observed secondary clinical parameters, including the insulin doses used to achieve target glucose levels, amount of time in the target glucose range, and significant hypoglycemic events.
The trial showed that the two 12-day courses of teplizumab were successful in preserving beta cell function. Furthermore, researchers observed other promising improvements. Participants who received the drug were able to reduce their insulin use and had a lowered risk of severe hypoglycemia. Continuous glucose monitors showed that participants in the experimental group also spent more time in their target glucose range. They were more likely to achieve the clinical threshold for disease remission. Finally, they also showed improvement in measures of quality of life based on scoring from the Pediatric Quality of Life Inventory Diabetes and Family Module, Hypoglycemia Fear Scale, and Diabetes Treatment Satisfaction Questionnaire.
Importantly, unlike other immune therapies for type 1 diabetes, teplizumab is not a chronic immune suppressant—it only requires two courses rather than continuous use. “This fulfills what we say in immunology as ‘operational tolerance,’” explains Herold. “In other words, you’ve given something for a brief period of time, and you fundamentally change the autoimmune response without continuously suppressing the immune system.”
Future studies may lead to improved type 1 diabetes therapies
At Yale, Herold’s team is exploring the therapeutic implications of the PROTECT trial. For instance, the researchers have also been involved in using beta cells derived from stem cells to replace those that have been destroyed by autoimmune processes. However, this process presents an obstacle—the body can similarly wipe out the replacement beta cells. Pairing this therapy with teplizumab could be a solution. “If teplizumab could stop the destruction of the replaced beta cells, we could help to restore normal metabolism in our patients,” says Herold.
While teplizumab significantly slows down the decline of beta cell function, its effects don’t last forever. Thus, Herold is also interested in combining the drug with other kinds of immune therapies to maximize the therapeutic benefits. “I could envision starting patients out with teplizumab when they’re first diagnosed, and then perhaps intermittently give them another immune suppressant that maintains the effect,” says Herold. “That’s another area we’re quite interested in pursuing.”
TrialNet, a NIDDK-sponsored research consortium, has ongoing trials, including trials evaluating the use of antithymocyte globulin (ATG), JAK inhibitors, and the combination of the biological therapies rituximab and abatacept in preventing and slowing the onset of type 1 diabetes. “There are a lot of opportunities here to try and come up with improved therapies for these diseases,” says Herold.