Zimislecel Therapy Achieves Insulin Independence in Majority of Type 1 Diabetes Patients in Phase 2 trial

In phase 2 of the FORWARD study, 83% of participants with type 1 diabetes achieved insulin independence a year after receiving zimislecel (formerly VX-880), an islet cell therapy developed by Vertex Pharmaceuticals. 10 out of 12 patients who received the full dose no longer required exogenous insulin, demonstrating promising potential for long-term diabetes management. These findings were published in The New England Journal of Medicine.

Zimislecel is an allogeneic, stem cell–derived islet-cell therapy designed to replace the insulin-producing beta cells destroyed by autoimmune activity in type 1 diabetes. This study which assessed the efficacy Zimislecel of enrolled 14 adults with long-standing type 1 diabetes, all of whom had undetectable C-peptide levels at baseline, indicating absent endogenous insulin production.

The participants were enrolled across three parts of the trial. In part A, two individuals received a half dose of zimislecel (0.4×10⁹ cells), with the possibility of a second dose within two years. In parts B and C, 12 patients received the full dose (0.8×10⁹ cells) via a single infusion into the portal vein. All participants were treated with glucocorticoid-free immunosuppressive regimens to prevent rejection of the implanted cells.

All 12 patients in parts B and C, who received the full zimislecel dose, experienced no severe hypoglycemic events between days 90 and 365 post-infusion. Moreover, they all achieved tight glucose control, reflected in glycated hemoglobin (HbA1c) levels under 7%. Most impressively, 10 of the 12 participants (83%) were insulin independent at day 365, meaning they no longer required external insulin to manage their blood sugar levels.

C-peptide was detectable in all participants post-treatment which suggests successful engraftment and functional islet cell restoration. This transformation occurred despite their complete lack of C-peptide at the beginning of the study. Neutropenia was the most common serious adverse event, occurring in 3 patients. Tragically, two deaths were reported: one from cryptococcal meningitis and another from progression of pre-existing severe neurocognitive impairment. 

The primary goal in part C was to ensure patients avoided severe hypoglycemic episodes while achieving meaningful improvements in blood sugar control. Secondary endpoints included safety and independence from insulin. Each participant's response was assessed using a 4-hour mixed-meal tolerance test to evaluate natural insulin production via C-peptide detection.

Overall, these preliminary results suggest zimislecel may represent a major advance in regenerative treatment for type 1 diabetes, restoring natural insulin production in most patients without the need for lifelong insulin therapy. Further studies are planned to confirm these findings and better understand the safety profile of this therapy.

Reference:

Reichman, T. W., Markmann, J. F., Odorico, J., Witkowski, P., Fung, J. J., Wijkstrom, M., Kandeel, F., de Koning, E. J. P., Peters, A. L., Mathieu, C., Kean, L. S., Bruinsma, B. G., Wang, C., Mascia, M., Sanna, B., Marigowda, G., Pagliuca, F., Melton, D., Ricordi, C., & Rickels, M. R. (2025). Stem cell–derived, fully differentiated islets for type 1 diabetes. The New England Journal of Medicine. https://doi.org/10.1056/nejmoa2506549