The US Food and Drug Administration (FDA) has approved the first diabetes prevention therapy, teplizumab, which delays the onset of type 1 diabetes by around two years in high-risk children.
The injectable immunotherapy, developed by Provention and to be marketed in conjunction with Sanofi, has been approved to delay the onset of stage 3 type 1 diabetes in patients eight years and older who currently have stage 2 type 1 diabetes.
Teplizumab is a monoclonal antibody that binds to the Fc receptor on CD8+ T lymphocytes to inhibit the autoimmune reaction that would otherwise destroy the insulin-producing beta cells in the pancreas.
According to the FDA the drug was granted approval under Priority Review and Breakthrough Therapy designations based on results from a randomised, double-blind trial with 76 children with stage 2 type 1 diabetes, who were deemed high risk because they had had two or more diabetes-related autoantibodies and evidence of dysglycaemia on oral glucose-tolerance testing
In the trial, patients randomly received teplizumab or a placebo once daily via intravenous infusion for 14 days. The primary measure of efficacy was the time from randomisation to development of stage 3 type 1 diabetes diagnosis.
The trial results, which were published in the NEJM in 2019, showed that over a median follow-up of 51 months, 45% of the 44 patients who received teplizumab were later diagnosed with stage 3 type 1 diabetes, compared to 72% of the 32 patients who received a placebo. The mid-range time from randomisation to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received teplizumab and 25 months for those who received a placebo.
“This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” the FDA said in a statement.
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said Dr John Sharretts, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research.
“The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The most common side effects of teplizumab in the trial were rash and lymphopenia, and the FDA approval comes with warnings and precautions, including premedicating and monitoring for symptoms of Cytokine Release Syndrome; risk of serious infections; decreased levels of lymphocytes; risk of hypersensitivity reactions; the need to administer all age-appropriate vaccinations prior to starting teplizumab; as well as avoiding concurrent use of live, inactivated and mRNA vaccines with teplizumab.
The lead investigator on the trial, Professor Kevan Herold of Yale School of Medicine explained that teplizumab could be used in combination with screening of school children for immune markers of type 1 diabetes to potentially delay the onset of diabetes for several years.
He said that in childhood, a few years delay in onset of diabetes could make a substantial difference in terms of maturity and ability to cope with a chronic disease, and also reduce the amount of exposure a patient has to the high blood sugars responsible for a wide range of complications.
“Some people ask, ‘If you’re still going to get diabetes, what’s the big deal?’ But if you’re an eight-year-old child, and the diagnosis of type 1 diabetes, the time at which you need to take insulin and follow a prescribed diet and monitor your blood sugar is delayed for two more years, that’s huge.”
Professor Herold said that for half of the patients, their delays will be longer than two years, with one high school student in his trial being diabetes free for 11 years after treatment, allowing him to attend college and find employment without the burden of type 1 diabetes.
“Don’t underestimate the importance of this for patients,” he said. “It’s hard to appreciate the significance of not having the disease unless you have it, but time without the disease is life changing.”