Expanded Approval for Teplizumab: What You Need to Know

There are over 2 million Americans living with Type 1 diabetes (T1DM), with 16% being children and adolescents. Treatment has historically hinged on symptom management and insulin replacement. But in 2022 teplizumab was approved as the first disease-modifying therapy for T1DM. 

In 2026, the FDA approved two new label expansions, making teplizumab more widely accessible to patients with T1DM.

Here’s what you need to know about teplizumab, its recent label expansions, and new safety information.

What is teplizumab?

Teplizumab is an anti-CD3 monoclonal antibody that delays onset and progression of Stage 3 T1DM through partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes. In 2022, it became the first FDA-approved disease-modifying therapy for T1DM in people 8 or older who have Stage 2 T1DM.

In 2026, new clinical trial data (more below) led to new approvals:

• Under a priority review process, the FDA approved a supplemental application to expand the indication to children as young as 1 year old. 

• The FDA also granted accelerated approval to delay decline in endogenous insulin production in children ages 8 to 17 years old with recently diagnosed Stage 3 T1DM. Continued approval for this accelerated approval is contingent on confirmatory trial results.

Clinical trial data

Data supporting the Stage 2 indication expansion was based on the phase 4 PETITE-T1D trial. This trial was designed to evaluate safety and assess pharmacokinetics of teplizumab in younger patients. This single-arm, open-label study enrolled 23 children ages 1 to 8 years old with Stage 2 T1DM who received a 14-day course. 

An interim analysis after 1 year was performed in 15 children. The estimated probability of not progressing to Stage 3 T1DM was 89.6% (95% CI, 64.3%-97.3%).

Although all children experienced a side effect (95.7% mild, 73.9% moderate), these side effects were generally self-limited and consistent with previous studies. Investigators concluded that teplizumab was safe and well tolerated in children less than 8 years old.

Data supporting the Stage 3 indication came from the PROTECT trial, a phase 3, randomized placebo-controlled trial. The trial enrolled 328 people ages 8 to 17 years old with Stage 3 T1DM that received two 12-day infusions 6 months apart. 

• Primary endpoint: The change from baseline in C-peptide levels 1 year after the second course of teplizumab. This was used as a surrogate marker for endogenous insulin production preservation. People treated with teplizumab had significantly higher stimulated C-peptide levels with a 59.3% difference between groups (95% CI, 0.09-0.17, p<0.001).

• Secondary endpoints: Insulin doses, hemoglobin A1C, time in target glucose range, and clinically significant hypoglycemic events. These did not reach statistical significance. The incidence of side effects did not change with the second course.

Clinical considerations

Teplizumab is the first drug of its kind in that it can stop Type 1 diabetes in its tracks. Healthcare providers should maintain a high clinical index of suspicion and check for antibodies when appropriate to ensure eligible patients are identified swiftly. The Pediatric Endocrine Society recommends following the ADA’s staging criteria (above) to determine eligibility.

The expanded indication for teplizumab will be especially impactful for younger patients. Targeting the autoimmune process earlier will ultimately improve outcomes and has the ability to change lives. However, given the typical timeline of disease progression, there is a tight window in which to initiate treatment.

The infusion schedule may be challenging for patients and their families, but many would likely be willing to manage this in order to halt disease progression. Similarly, healthcare teams will need to come up with detailed systems and care models to efficiently manage the infusion schedules for their patients. This is particularly true for pediatric patients, since in-home infusions are not recommended for them.

There are no data on teplizumab in pregnancy. So it’s best to avoid prescribing for those who are pregnant, or who may become pregnant, as monoclonal antibodies can be transported across the placenta.

Lastly, while the recent approvals are encouraging, these are based on relatively small population numbers. Clinicians should anticipate further clinical updates as post-marketing data on both the safety and efficacy of teplizumab are published.

Safety signals and monitoring

Teplizumab carries a new boxed warning for viral reactivation. It is contraindicated in immunocompromised people or in those with an active viral infection (such as Epstein-Barr Virus (EBV) or cytomegalovirus (CMV)).

Common teplizumab side effects include:

• Lymphopenia 

• Leukopenia

• Neutropenia

• Rash

• Vomiting

• Diarrhea

• Elevated liver enzymes

• Headache

Serious adverse effects include:

• Viral reactivation

• Cytokine release syndrome (CRS)

• Serious infections

• Severe lymphopenia

• Hypersensitivity

To reduce the risk of CRS, premedication for the first 5 days with NSAIDs or acetaminophen and an antihistamine is recommended alongside monitoring liver enzymes and bilirubin.

Special scenarios: Vaccination

There are additional vaccine considerations with teplizumab. Healthcare professionals should offer all age-appropriate vaccines before starting treatment.

• Give live-attenuated vaccines at least 8 weeks prior to treatment.

• Give inactivated or mRNA vaccines at least 2 weeks prior to treatment. 

The safety of vaccination during teplizumab therapy has not been studied, and it’s possible teplizumab may interfere with vaccine response. For this reason vaccines should not be given during the treatment period. It’s also a good idea to defer vaccines after treatment completion:

• Defer live-attenuated vaccines up to 1 year after the final treatment course. 

• Defer inactivated and mRNA vaccines up to 6 weeks after each treatment course. 

Because Stage 3 treatment involves two courses 6 months apart, this extended timeline can affect the ability to keep a child on track with age-appropriate vaccines. For this reason, it’s important to collaborate with pediatricians on vaccine planning in advance and encourage household members to be up to date on COVID-19 and influenza vaccination as an added layer of protection.

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Written by:

Ferras Bashqoy, PharmD, BCCCP, BCPPS

Ferras Bashqoy, PharmD, BCCCP, BCPPS, is a clinical pharmacotherapy specialist in the Neonatal Intensive Care Unit at Hassenfeld Children’s Hospital in NYC. He enjoys working with preterm newborns, as they are small but mighty.

Edited by:

Mandy Armitage, MD

Mandy Armitage, MD, has combined clinical medicine with her passion for education and content development for many years. She is co-executive director at Nonclinical Physicians Network and has served as medical director for the health technology companies HealthLoop (now Get Well) and Doximity.

Reviewed by:

Farah Naz Khan, MD

Farah Naz Khan, MD, is a board-certified physician at the UW Medicine Diabetes Institute and a clinical assistant professor of metabolism, endocrinology, and nutrition at the University of Washington.

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