Diabetes Dialogue: PROTECT Data and Teplizumab in Newly Diagnosed T1D

Less than a year after receiving approval as the first therapy in US Food and Drug Administration history for delaying the onset of type 1 diabetes, teplizumab (Tzield) is once again making headlines with the results of the PROTECT trial.

Results of the trial, which assessed the effects of teplizumab in patients with newly diagnosed type 1 diabetes, suggested use of the agent was associated with a significant reduction in the decrease in mean C-peptide levels, a marker of beta-cell function, at 78 weeks relative to those who received placebo therapy.¹

“These new results build on the findings from multiple studies across different stages of the disease process, further supporting TZIELD’s potential to modulate the progression of [type 1 diabetes],” said Kevan Herold, MD, the C.N.H. Long Professor of Immunobiology and of Medicine at Yale School of Medicine, in a statement from Sanofi.²

The FDA approval of teplizumab for delaying the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes on November 17, 2022 ushered in a new era of diabetes management. This approval was based on results from the TN-10 trial.³

PROTECT trial was a phase 3, randomized, placebo-controlled trial aimed at assessing the effect of teplizumab use in people with stage 3 type 1 diabetes. With this in mind, the trial enrolled patients and randomized them in a 2:1 ratio to teplizumab or matching placebo for 2, 12-day courses. Investigators pointed out randomization was stratified according to the peak C-peptide level and age.¹

In addition to achieving its primary endpoint of a significantly less decrease in mean C-peptide levels following a 4-hour mixed-meal tolerance test (difference in least-squares means of 0.13 pmol/mL; 95% CI, 0.09 to 0.17; P<0.001). the trial also provided insight into the effects using multiple secondary outcomes of interest:

• HbA1c was rapidly controlled in both groups and did not differ between groups through week 78.¹
• Time in range favored teplizumab, but failed to reach statistical significance (4.71 percentage points; 95% CI, -1.72 to 11.15).¹
• Estimated mean daily insulin doses were 0.46 units and 0.59 units per kilogram per day for the teplizumab and placebo groups, respectively (difference, 0.13 units per kilogram per day; 95% CI, –0.28 to 0.02).¹

Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, spotlight the data in the latest episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives.

Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. Ramos EL, Dayan CM, Chatenoud L, et al. Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes [published online ahead of print, 2023 Oct 18]. N Engl J Med. 2023;10.1056/NEJMoa2308743. doi:10.1056/NEJMoa2308743
2. 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. Sanofi. October 25, 2023. Accessed October 18, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-10-18-08-45-00-2762096.