For more than 30 years, Yale endocrinologist Kevan Herold has been researching treatments for Type 1 diabetes (T1D). For just as long, he's been the principal investigator for multiple clinical trials involving a drug called teplizumab, also known as Tzield, a targeted immunotherapy designed to alter the underlying cause of the chronic condition.
This month, the U.S. Food and Drug Administration (FDA) approved teplizumab as a treatment for pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. The FDA approved the use of the drug based on the recent PROTECT study, which confirmed that drug treatment could delay the loss of the body's own insulin production.
The drug is now available and can be given to patients. In 2022, teplizumab was approved by the FDA for pediatric patients as young as one who are at risk of developing diabetes. It was shown to delay the onset of stage 3 T1D.
"This is paradigm shifting for the field," said Herold, the C.N.H. Long Professor of Immunobiology and of Medicine (Endocrinology) at Yale School of Medicine (YSM). "What it has been shown to do in all of the clinical trials is to delay the progression of the disease - the loss of insulin-producing cells that is the cause of Type 1 diabetes. Importantly, teplizumab does not cause chronic immune suppression."
T1D develops in stages, and those stages are determined by blood sugar levels and the presence of autoantibodies, a type of protein in the blood. The immune system makes autoantibodies and lymphocytes which mistakenly attack the body's own cells. In people with T1D, these immune cells target cells in the pancreas that produce insulin. When a person has Stage 3 T1D, they lose a significant number of the insulin producing cells and experience symptoms like fatigue, frequent urination, and thirst due to high blood sugar. In this stage, people need insulin therapy for survival and to manage blood sugar levels.
"Our current treatment paradigm is that kids with diabetes need to be thinking about diabetes all the time, right?," said Jennifer Sherr, a professor in pediatrics (endocrinology) and medical director of the pediatric diabetes program at YSM, who has been leading the clinical deployment of teplizumab in the pediatrics department. "They have to be thinking about glucose levels, delivering insulin, what they're going to eat, their physical activity level."
Herold added: "There is no other treatment for Type 1 diabetes other than diet and insulin. That's been true for the last 100 years, since the discovery of insulin in 1922."
With teplizumab, which helps preserve the abilty of pediatric patients to make their own insulin rather than being completely dependent on insulin that you inject, Sherr says those patients experience less hypoglycemia and other symptoms. "We know if your body continues to produce your own insulin, instead of the road being really bumpy, it's a little bit smoother to travel," she said.
Since the late 1980s, Herold has led research on the drug from animal models in the lab all the way through testing with patients and now FDA approval. The PROTECT study evaluated whether teplizumab could preserve the function of beta cells - which produce insulin - in recently diagnosed youth. They found that the drug did achieve this, but it also found an improvement in other clinical parameters like reduced reliance on insulin.
The randomized, double-blind, placebo-controlled trial enrolled children and adolescents with T1D who had received their diagnosis within the previous six weeks. They all went through an intiail screening process to evaluate their beta cell function. Then, certain participants either received a 12-day course of intravenous teplizumab or a placebo. Six or 12 months later, they all received a second 12-day course.
After 18 months, the researchers assessed changes in beta cell function, discovering that teplizumab - a humanized monoclonal antibody - preserved the function of these cells which, in turn, helped slow down the loss of the body's insulin production. Researchers also saw other promising improvements, including participants being able to reduce their insulin use and having a lower risk of severe hypoglycemia.
