FDA Approves Teplizumab-mzwv for Children With Newly Diagnosed Stage 3 Type 1 Diabetes

The FDA has granted accelerated approval to teplizumab-mzwv (Tzield; Sanofi) to delay the decline in endogenous (own) insulin production in children and adolescents aged 8 to 17 years recently diagnosed with stage 3 type 1 diabetes (T1D), according to a news release from Sanofi.¹

The decision makes teplizumab the first disease-modifying therapy approved for patients newly diagnosed with stage 3 T1D. It builds on the drug's original 2022 approval to delay disease onset in patients with stage 2 T1D; teplizumab’s age range in that indication was recently expanded to patients as young as 1 year. In the release announcing the new indication, Sanofi representatives noted that teplizumab is not effective as a disease-modifying therapy in non-autoimmune dysglycemic conditions.^1,2

“Practically all patients with new-onset stage 3 T1D should be offered therapy unless there is an underlying condition that would prevent the drug administration,” Kevan Herold, MD, CNH Long professor of immunobiology and medicine at Yale School of Medicine and co-author of the PROTECT clinical trial, said in an interview. “There are no other treatments for T1D other than diet and insulin and this is the only therapy that treats the underlying cause of the disease.”

PROTECT Trial Data Support Approval

The approval is supported by data from the phase 3 PROTECT trial (NCT03875729), along with safety data from teplizumab's broader clinical development program, which has treated more than 900 patients to date. PROTECT was a randomized, double-blind, placebo-controlled, multinational trial conducted at 61 sites in the United States, Canada, and Europe that enrolled 328 children and adolescents diagnosed with stage 3 T1D within the preceding 6 weeks. Patients were randomized 2:1 to receive teplizumab (n = 217) or placebo (n = 111), each given as a 12-day course of daily intravenous infusions at randomization, followed by a second 12-day course approximately 26 weeks later; all participants continued standard-of-care insulin therapy throughout the study.^1,3,4

At the primary end point—change from baseline in stimulated C-peptide levels (area under the curve following a 4-hour mixed-meal tolerance test) at week 78—patients treated with teplizumab had a significantly smaller decline than those on placebo (least-squares mean difference, 0.13 pmol/mL; 95% CI, 0.09-0.17; P < .001), representing a 59.3% relative difference between groups favoring teplizumab. Investigators also found that 94.9% of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol/mL or higher at week 78, compared with 79.2% of those who received placebo. Key secondary end points, including daily insulin dose, glycated hemoglobin, percentage of time in target glucose range, and clinically important hypoglycemic events, showed numerical trends favoring teplizumab but did not reach statistical significance.^1,3

Safety Profile Consistent With Prior Studies

The most common adverse reactions observed in PROTECT were lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminases, and headache, consistent with teplizumab's established safety profile. More serious risks, including cytokine release syndrome and, rarely, life-threatening viral reactivation, have also been reported; patients who are immunocompromised are at increased risk for viral reactivation. In the trial, patients received premedication with ibuprofen or acetaminophen, an antihistamine, an antiemetic, or all 3, for at least the first 5 days of each infusion course.^1,3

Because this indication was granted under the FDA's accelerated approval pathway based on a surrogate endpoint (C-peptide decline) reasonably likely to predict clinical benefit, continued approval may be contingent on verification in a confirmatory trial. Sanofi has initiated the phase 3 BETA-PRESERVE trial (NCT07088068), which is currently enrolling participants.¹

Expert Reaction: What This Means for Pharmacists

Aaron J. Kowalski, PhD, CEO of Breakthrough T1D, said the approval gives clinicians a therapy that "targets the autoimmune and progressive nature of stage 3 type 1 diabetes," adding that roughly 64,000 people are diagnosed with T1D in the United States each year and that this approval provides a new option for those diagnosed at stage 3, when many patients first begin experiencing symptoms.¹

Teplizumab, a CD3-directed monoclonal antibody, does not replace insulin therapy; it is intended to be used alongside standard-of-care insulin management to preserve residual beta-cell function in patients diagnosed within weeks of symptom onset. Pharmacists in specialty, health-system, and pediatric endocrinology settings should be prepared to counsel families on the infusion schedule, the importance of premedication adherence, and monitoring for infection-related adverse events, including viral reactivation, given the drug's effect on lymphocyte counts.^1,5

In an interview with Pharmacy Times, Jennifer Goldman, PharmD, CDCES, BC-ADM, FCCP, professor of pharmacy practice and clinical pharmacist at Massachusetts College of Pharmacy and Health Sciences, discussed key pharmacist responsibilities when prescribing teplizumab.⁶

“We can help identify eligible patients, coordinate lab orders, interpret results, and really guide the next steps, whether that's more testing or a referral to an infusion center,” Goldman said. “Equally critical is educating clinical staff about the importance of early identification and consistent monitoring of these high-risk individuals.”⁶

Given that the indication was approved on a surrogate endpoint and several clinical secondary measures did not reach significance, pharmacists may also play a role in setting realistic expectations with patients and caregivers about what the therapy can, and cannot, be expected to achieve in the near term.^1,2

Insights From Kevan Herold, MD

Pharmacy Times: Now that teplizumab’s approval extends to children newly diagnosed with stage 3 T1D, how should pediatric prescribers and pharmacists think about the treatment window for identifying and referring eligible patients?

Kevan Herold, MD: My view is that practically all patients with new-onset stage 3 T1D should be offered therapy unless there is an underlying condition that would prevent the drug administration. There are no other treatments for T1D other than diet and insulin, and this is the only therapy that treats the underlying cause of the disease. There is clinically significant insulin production at the time of onset, but it is lost with time and cannot be recovered. The very consistent findings from all of the trials—including the ones that I did beginning in the 1990s—have shown preservation of beta cell function. So, the progression of disease is slowed. In addition, reduced insulin requirements have been a consistent finding.

There are 2 additional items to consider when evaluating the therapy. Some patients have particularly robust responses. There are patients in the prevention trial that led to the approval in 2022 for those at risk that have gone beyond 10 years after a single course of drugs. Second, there is an ease of management in patients with residual beta cell function compared to those who are completely dependent on exogenous insulin. The time in range is generally better with residual insulin production than without, and certainly the frequency of severe hypoglycemia, the major limiting factor for normal glucose control, is less. This is a paramount concern for parents who are managing the diabetes of their children as well as family members for all patients. It is challenging to capture all of this, but comparing the reduced variability and less frequent hypoglycemia of type 2 diabetes versus type 1 diabetes illustrates the significance of residual insulin production.

REFERENCES

1. Sanofi. Sanofi's Tzield approved in the US as the first disease-modifying therapy for patients recently diagnosed with stage 3 type 1 diabetes. News release. June 12, 2026. Accessed June 16, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-12-22-09-58-3311349

2. Ferruggia K. FDA extends teplizumab-mzwv approval to delay stage 3 type 1 diabetes in children as young as 1 year. Pharmacy Times. Published April 22, 2026. Accessed June 16, 2026. https://www.pharmacytimes.com/view/fda-expands-teplizumab-mzwv-approval-to-delay-stage-3-type-1-diabetes-in-children-as-young-as-1-year

3. Ramos EL, Dayan CM, Chatenoud L, et al. Teplizumab and β-cell function in newly diagnosed type 1 diabetes. N Engl J Med. 2023;389(23):2151-2161. doi:10.1056/NEJMoa2308743

4. Recent-onset type 1 diabetes trial evaluating efficacy and safety of teplizumab (PROTECT). ClinicalTrials.gov identifier: NCT03875729. Accessed June 16, 2026. https://clinicaltrials.gov/study/NCT03875729

5. McGovern G. FAQ: Teplizumab and its expanded FDA indication. Pharmacy Times. Published May 7, 2026. Accessed June 16, 2026. https://www.pharmacytimes.com/view/faq-teplizumab-and-its-expanded-fda-indication

6. Goldman J, McGovern G. Pharmacists play crucial role in screening and educating patients with type 1 diabetes. Pharmacy Times. Published August 11, 2025. https://www.pharmacytimes.com/view/pharmacists-play-crucial-role-in-screening-and-educating-patients-with-type-1-diabetes