Teplizumab, an anti-CD3 monoclonal antibody, delayed the median onset of stage 3 T1D by approximately 2 years compared to placebo in a pivotal clinical trial.
Teplizumab, an anti-CD3 monoclonal antibody, was approved today by the US Food and Drug Administration (FDA) to delay the onset of stage 3 type 1 diabetes (T1D) in adults and children aged ≥8 years who are at high risk of disease progression.
Among findings leading to the approval, teplizumab delayed the median onset of stage 3 T1D by approximately 2 years compared to placebo, according to Provention Bio.
"Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients," said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA's Center for Drug Evaluation and Research in the FDA announcement. "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 agent, administered by intravenous infusion once daily for 14 consecutive days, disrupts T-cell-mediated autoimmune destruction of pancreatic beta cells and is the first immunomodulatory treatment for impeding progression to stage 3 T1D in persons with stage 2 T1D, ie, those who have islet autoantibodies and evidence of dysglycemia, but do not yet meet the criteria for a clinical diagnosis of T1D.
FDA approval was based on the randomized, double-blind, event-driven placebo-controlled TN-10 study which assessed the efficacy of teplizumab to delay T1D in stage 2 patients, defined by the presence of ≥2 T1D-related autoantibodies and dysglycemia.
Investigators enrolled 76 patients aged 8 to 49 years of whom 72% were younger than age 18 years. The participants were randomized to receive a single 14-day course of either teplizumab (n=44) or placebo (n=32).
Median follow-up was 923 days at which point 50% of participants in the teplizumab group remained diabetes free, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).
"The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes," according to the FDA statement.
The most common side effects of teplizumab vs placebo included lymphopenia (73% vs 6%), rash (36% vs 0%), leukopenia (221% vs 0%), and headache (11% vs 6%).
“The onset of Stage 3 T1D is a life-changing moment - once insulin-producing cells are no longer capable of maintaining normal glycemic control, this irreversible condition can lead to the need, in just one year, for a patient, 1,460 finger sticks to check blood glucose levels, around 1,100 insulin injections, and experiencing an average of 127 episodes of hypoglycemia. These complications can cause stress, fear, and anxiety in patients as they work to manage their T1D diagnosis and provide perspective on the meaning of a delay in the onset of Stage 3 T1D," said Eleanor Ramos, MD, Provention Bio chief medical officer.
The teplizumab label contains warnings and precautions, including premedicating against and monitoring for cytokine release syndrome, the risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines. Patients should, however, be current with all age-appropriate vaccinations before initiating teplizumab treatment.
Teplizumab received both priority review and breakthrough drug designations from the FDA. After an FDA advisory panel voted for recommending the drug’s approval in May 2021, Provention Bio received a complete response letter in July. The FDA subsequently accepted the company’s resubmission of the biologics license application in March 2022.