Phase 3 Data Show Teplizumab Slows T1D Progression in Children, Adolescents

Teplizumab is approved by the FDA to delay the onset of clinical stage 3 T1D in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed T1D can prevent disease progression is unknown.

New data presented at the annual conference of the International Society for Pediatric and Adolescent Diabetes (ISPAD) found that teplizumab-mzwv (Tzield) was effective in slowing the progression of type 1 diabetes (T1D) in newly diagnosed children and adolescents with stage 3 T1D. The full data was also simultaneously published in the New England Journal of Medicine.

The phase 3 PROTECT study was a randomized, double blind, placebo-controlled, multi-national trial that assessed the safety and efficacy of teplizumab-mzwv vs placebo over a 78-week study period

The data comes after the drug was approved by the FDA in November 2022 as the first and only therapy to delay the onset of stage 3 T1D in adult and pediatric patients aged 8 years and older with stage 2 T1D. Teplizumab was also among Clarivate’s Drugs to Watch List for 2023.

“Type 1 diabetes is a chronic autoimmune disease, driven by the destruction of the insulin-producing beta cells, and as such, beta cell preservation remains a meaningful unmet need for all patients with diabetes. These new results build on the findings from multiple studies across different stages of the disease process, further supporting [teplizumab's] potential to modulate the progression of T1D,” commented Kevan Herold, MD, the primary investigator and C.N.H. long professor of immunobiology and of medicine (endocrinology), Yale School of Medicine, in a statement from Sanofi, the drug’s manufacturer.

Researchers enrolled 328 children and adolescents aged 8-17 years who were diagnosed with stage 3 T1D in the preceding 6 weeks. The patients were randomized 2:1 to receive either teplizumab (n = 217) or placebo (n = 111). Participants received a first course of 12 daily infusions at randomization, followed by a second course of 12 daily infusions after week 26 (about 6 months).

The primary objective was to determine whether the teplizumab can slow down beta cell loss and preserve beta cell function measured by C-peptide compared with placebo from baseline to week 78. Secondary endpoints included HbA1c, time in range (TiR) as measured with a continuous glucose monitor, clinically important hypoglycemia events, and exogenous insulin use. Adverse events, overall safety aspects, pharmacokinetics, and immunogenicity were also assessed.

Results showed that patients receiving teplizumab had significantly less decrease in mean C-peptide levels, which was determined following a 4-hour mixed-meal tolerance test. 94.9% of participants in the experimental group maintained peak C-peptide levels of ≥ 0.2 pmol/mL compared with. 79.2% of those in the placebo group (95% CI, 0.09-0.17; P < .001).

Additionally, compared with the placebo group, the experimental group experience numerically lower mean insulin dose (95% CI, -0.28 to 0.02), comparable changes in mean HbA1c (95% CI, -0.42 to 0.24), numerically higher mean time in range (95% CI, -1.72 to 11.15), and similar mean rates of overall clinically important hypoglycemic events. (95% CI, 0.74-1.64).

The safety results were consistent with previous data from use of teplizumab in its currently approved indication and other prior clinical studies assessing the drug. No new safety signals were identified.

Adverse events (AEs) of special interest occurred in 29% of patients administered teplizumab and 21.6% of those who received the placebo, the most frequent of which was hypoglycemia (teplizumab, 13.4%; placebo, 16.2%) Other common AEs were headache, nausea, rash, lymphopenia, and vomiting. Serious AEs were similar between groups (teplizumab vs placebo, 5.5% vs 5.4%), of which cytokine release syndrome (1.4% vs 0.0%, respectively) and infection (0.0% vs 2.7%, respectively) were the most commonly reported.

Reference

Tzield phase 3 data presented at ISPAD shows potential to slow the progression of Stage 3 type 1 diabetes in newly diagnosed children and adolescents; full data simultaneously published in the New England Journal of Medicine. News release. Sanofi; October 18, 2023. Accessed October 20, 2023. https://www.news.sanofi.us/2023-10-18-TZIELD-R-Phase-3-data-presented-at-ISPAD-shows-potential-to-slow-the-progression-of-Stage-3-type-1-diabetes-in-newly-diagnosed-children-and-adolescents-full-data-simultaneously-published-in-The-New-England-Journal-of-Medicine