The US Food and Drug Administration (FDA) has granted accelerated approval to teplizumab-mzwv (Tzield) to delay the decline in endogenous insulin production in children aged 8 to 17 years recently diagnosed with stage 3 type 1 diabetes (T1D), making it the first disease-modifying therapy approved in this newly diagnosed population, according to Sanofi.¹
Teplizumab, a CD3-directed monoclonal antibody, was first approved in November 2022 to delay the onset of stage 3 T1D in adults and children aged 8 years and older with stage 2 T1D.¹ In April 2026, the FDA expanded the stage 2 indication to include children aged 1 year and older.¹ The June 12, 2026 accelerated approval extends the label to address a distinct clinical moment: the period immediately following a stage 3 diagnosis, when beta-cell loss is already clinically apparent and insulin therapy has begun.
“We now have a novel therapy that targets the autoimmune and progressive nature of stage 3 type 1 diabetes,” said Aaron J. Kowalski, PhD, CEO of Breakthrough T1D. “Approximately 64,000 people are diagnosed with T1D every year. We are excited that the approval of Tzield in this indication provides a treatment option for certain patients diagnosed in stage 3 T1D, which is when many start experiencing common symptoms of the disease.”
Teplizumab efficacy in PROTECT: trial design and primary endpoint
The accelerated approval was supported by data from the PROTECT phase 3 study (NCT03875729), a randomized, double-blind, placebo-controlled, multinational trial enrolling 328 children and adolescents aged 8 to 17 years with a clinical stage 3 T1D diagnosis within the preceding 6 weeks.¹ Participants were assigned 2:1 to teplizumab (n=217) or placebo (n=111). Each received a first course of 12 daily intravenous infusions at randomization, followed by a second 12-dose course at 26 weeks; all participants received standard-of-care insulin as required.¹
The primary endpoint assessed beta-cell function via C-peptide levels measured as the area under the curve (AUC) during a 4-hour mixed-meal tolerance test. Teplizumab significantly slowed the decline in mean C-peptide compared with placebo at trial completion (difference in least-squares means: 0.13 pmol/mL; 95% CI: 0.09–0.17; P < .001).¹ This reduction in C-peptide decline served as the surrogate endpoint reasonably likely to predict clinical benefit, consistent with the FDA's accelerated approval pathway for serious conditions with unmet need.
Broader evidence supporting the approval included data from teplizumab's full clinical development program, which encompassed more than 900 patients who received the drug across studies.¹ Real-world treatment pattern data from the TEPLI-REAL study, the first observational analysis of teplizumab use since its 2022 US launch, also provided supporting context for the drug's clinical uptake.²
Teplizumab safety profile and accelerated approval requirements
According to Sanofi, adverse events observed in the PROTECT study were consistent with those seen in prior teplizumab trials.¹ The most common adverse reactions included lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminases, and headache.¹ Serious events including cytokine release syndrome and life-threatening cases of viral reactivation have been reported with teplizumab; immunocompromised patients are at heightened risk for viral reactivation.¹
As a condition of accelerated approval, continued availability for the stage 3 indication will be contingent on verification of clinical benefit in confirmatory trials.¹ The BETA-PRESERVE phase 3 study (NCT07088068) has been initiated and is currently enrolling participants to fulfill this requirement.¹
“Tzield will now offer a new pathway in the treatment paradigm of stage 3 T1D, one that we hope will further enable healthcare providers in the US to take a more proactive approach to disrupt the underlying autoimmune attack against insulin-producing beta cells,” said Christopher Corsico, Global Head of Development, Sanofi.¹
Teplizumab is also approved to delay the onset of stage 3 T1D in patients with stage 2 disease across multiple international markets including the UK, EU (as Teizeild), China, Australia, Canada, and several countries in the Middle East, Latin America, and Switzerland; regulatory reviews are ongoing in additional jurisdictions.¹
References
Sanofi. Sanofi's Tzield approved in the US as the first disease-modifying therapy for patients recently diagnosed with stage 3 type 1 diabetes. Published June 12, 2026. Accessed June 12, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-12-22-09-58-3311349
