Sanofi's First-in-Class Therapy Tzield Shows Promise in Slowing Progression of Stage 3 Type 1 Diabetes in Phase 3 Trial Published in NEJM

▎WuXi

Edited by Kant Content Team

Sanofi today announced the latest data of Tzield (teplizumab) in the phase 3 clinical trial named PROTECT. The results showed,Tzield Slows Beta-Cell Loss and Preserves Beta-Cell Function in Children and Adolescents Aged 8-17 with Stage 3 Autoimmune Type 1 Diabetes (T1D) Diagnosed in the Previous 6 Weeks, Compared to Placebo.The complete data has been simultaneously published in The New England Journal of Medicine (NEJM).

T1D is a chronic autoimmune disease in which the body's ability to regulate blood glucose levels is affected due to the gradual destruction of insulin-producing β-cells by the autoimmune system. T1D progresses through three stages, with the third stage also known as the clinical stage. At this point, blood glucose levels rise to clinically significant hyperglycemia, and many individuals exhibit the classic symptoms associated with T1D onset: increased thirst, frequent urination, unexplained weight loss, blurred vision, and overall fatigue. Managing T1D at this stage requires daily and intensive insulin replacement therapy.

Tzield is a “first-in-class” anti-CD3 monoclonal antibody that has the potential to bind to specific immune cells, preventing them from attacking insulin-producing cells.In November 2022, it received approval from the U.S. FDA for the treatment of patients with stage 2 T1D (who have not yet exhibited clinical symptoms of diabetes); however, whether it can be used to treat patients with stage 3 T1D remains unconfirmed.

The Phase 3 clinical trial, named PROJECT, is a randomized, double-blind, placebo-controlled study. Newly diagnosed pediatric or adolescent patients received two 12-day treatment courses. The trial results showed,Tzield achieved the primary endpoint of the study, significantly slowing the decline in average C-peptide levels at the end of the trial (78 weeks) compared to placebo. In the Tzield group, 94.9% of participants maintained peak C-peptide levels ≥0.2 pmol/mL, compared to 79.2% in the placebo group (p

C-peptide is a biomarker of β-cell function. This significant difference suggests that Tzield has the potential to slow the progression of type 1 diabetes in this population. Although the key secondary endpoints of the study did not reach statistical significance, numerical trends favoring Tzield were observed in relevant clinical parameters. Compared with the placebo group, patients in the Tzield group required numerically fewer units of insulin and spent a numerically longer time with blood glucose levels within the target range. The overall incidence of glycated hemoglobin (HbA1c) reduction and clinically significant hypoglycemic events was similar between the two study groups.

References:

[1] Press Release: 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 NEJM. Retrieved October 18, 2023, from https://www.sanofi.com/en/media-room/press-releases/2023/2023-10-18-08-45-00-2762096