What is the availability of Teplizumab (anti-CD3 monoclonal antibody) for patients with Stage 2 type 1 diabetes?

Teplizumab Availability for Stage 2 Type 1 Diabetes

Teplizumab-mzwv (TZIELD™) is FDA-approved and commercially available in the United States and seven other countries for patients aged ≥8 years with Stage 2 type 1 diabetes to delay progression to Stage 3 symptomatic disease. 1, 2, 3

Regulatory Approval Status

• Teplizumab received FDA approval in November 2022 for delaying the onset of Stage 3 type 1 diabetes in adults and pediatric patients 8 years of age and older with Stage 2 type 1 diabetes 2, 3
• The drug is approved in the USA and seven additional countries, making it accessible in multiple international markets 4
• This represents the first and only approved therapy specifically indicated for delaying clinical type 1 diabetes progression 1, 3

Patient Eligibility Criteria

• Patients must be ≥8 years of age with documented Stage 2 type 1 diabetes 1, 2
• Stage 2 type 1 diabetes is defined by the presence of multiple islet autoantibodies plus dysglycemia without clinical symptoms 5
• The approval was based on a pivotal trial (Study TN-10) in relatives of people with type 1 diabetes, where 44 individuals received teplizumab and 32 received placebo 1

Treatment Setting Requirements

• Administration must occur in a specialized setting with appropriately trained personnel capable of managing infusion reactions and immune-mediated adverse events 1, 5
• The treatment consists of a 14-day intravenous infusion course 1, 2
• Facilities must have expertise in recognizing and treating cytokine release syndrome, lymphopenia, and hypersensitivity reactions 2

Expanding Access to Younger Children

• A post-marketing study (PETITE-T1D) is currently evaluating safety in children <8 years of age, with interim results showing the drug was safe and well tolerated in 23 children aged 1.7-6.8 years 4
• This FDA-mandated post-marketing requirement may lead to expanded approval for younger pediatric patients in the future 4
• Mean participant age in the pediatric study was 4.8 years, with no grade 4 or 5 treatment-emergent adverse events reported 4

Clinical Efficacy Supporting Availability

• Teplizumab delayed median time to Stage 3 diagnosis from 24.4 months to 48.4 months, representing a doubling of disease-free time 1, 5
• Stage 3 diabetes developed in 43% of teplizumab-treated patients versus 72% of placebo patients (HR 0.41,95% CI 0.22-0.78) 1, 5
• The estimated probability of lack of progression to Stage 3 was 89.6% (95% CI 64.3%, 97.3%) in the pediatric study at interim analysis 4

Predictors of Response

• Presence of HLA-DR4 predicts superior response (HR 0.20,95% CI 0.09-0.45) 1, 5
• Absence of HLA-DR3 predicts better outcomes (HR 0.18,95% CI 0.07-0.45) 1, 5
• Absence of anti-zinc transporter 8 antibody is associated with enhanced response (HR 0.07,95% CI 0.02-0.26) 1, 5

Safety Profile Affecting Availability

• The most common adverse reaction is transient lymphopenia (73%), with nadir on day 5 of the 14-day course 1, 5, 2
• Rash develops in 36% of patients, with higher incidence in those who develop anti-teplizumab-mzwv antibodies 1, 5, 2
• Approximately 57% of treated patients developed anti-teplizumab-mzwv antibodies, with 46% developing neutralizing antibodies 2
• Most adverse events are mild to moderate and occur primarily during drug administration 4, 6

Current Guideline Recommendations

• The American Diabetes Association's 2025 Standards of Care (Recommendation 3.15) states that teplizumab-mzwv infusion should be discussed with selected individuals aged ≥8 years with Stage 2 type 1 diabetes 1, 5
• The 2024 ADA guidelines recommended that teplizumab "should be considered" in this population, which was strengthened to "should be discussed" in the 2025 update 1

Practical Access Considerations

• Treatment requires specialized diabetes centers with infusion capabilities and trained personnel, which may limit geographic availability 1, 5
• The 14-day infusion course requires significant patient and family commitment, with daily visits to the treatment facility 1, 2
• Patients must be monitored for lymphopenia, rash, and cytokine release syndrome throughout the treatment course 2

Critical Pitfall to Avoid

• Do not delay discussion of teplizumab with eligible Stage 2 patients, as the drug provides the only approved disease-modifying therapy to delay progression to symptomatic diabetes, and earlier intervention may provide greater benefit 1, 5