Zimislecel Enables Insulin Independence in 10 Participants with Type 1 Diabetes

Ten of 12 participants with type 1 diabetes (T1D) that received a full dose of zimislecel, Vertex Pharmaceutical’s islet cell therapy formerly known as VX-880, in phase 2 of the FORWARD study remain insulin-independent after 1 year of follow-up.1

These findings were presented at the 2025 American Diabetes Association (ADA) Scientific Sessions, held June 20-23, in Chicago, Illinois, by investigator Michael Rickels, MD, MS, Willard and Rhoda Ware professor in diabetes and metabolic diseases, Division of Endocrinology, Diabetes & Metabolism, University of Pennsylvania Perelman School of Medicine, and simultaneously published in New England Journal of Medicine.1,2

"Stem cell therapy is showing tremendous promise in transforming type 1 diabetes care, offering real hope for insulin independence,” Marlon Pragnell, the ADA’s vice president of research and science., said in a statement.3 "With advances in genetic engineering, these therapies may one day also evade immune attack—eliminating the need for immunosuppressive drugs."

In phase 2 of FORWARD, 12 participants with T1D received a portal vein infusion of 0.8×109 cells zimislecel under a standard immunosuppression drug regimen. After infusion, all participants had engraftment and islet function, as evidenced by the detection of C-peptide, which was undetectable at baseline. All 12 were free of severe hypoglycemic events, had an HbA1c level of less than 7%, and spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter). Ten (83%) achieved insulin independence and were not using exogenous insulin at day 365.1

“It’s remarkable to see 12 out of 12 patients with baseline HbA1c above 7% and multiple severe hypoglycemic events reach consensus targets for glycemic control by both HbA1c and time in range as well as elimination of severe hypoglycemic events,” Rickels said in another statement.4 “As I think about my patients and the unmet need in the type 1 diabetes community, the results we’ve seen so far for restoring endogenous insulin secretion with a stem cell-derived islet therapy bring me hope and confidence for a transformative treatment option for individuals with type 1 diabetes in the not-so-distant future.”

Neutropenia was the most common serious adverse event, occurring in 3 of 14 participants in the safety set.1 One death, caused by cryptococcal meningitis occurred in phase 2 and was deemed related to the immunosuppressive regimen. This death followed one other in the phase 1 by severe dementia with agitation owing to the progression of preexisting neurocognitive impairment.

FORWARD is now in phase 3 and aims to complete enrollment and dosing of approximately 50 participants throughout 2025. Vertex also plans to launch a study evaluating zimislecel in around 10 adults with T1D who are already receiving immunosuppressive therapy following a prior kidney transplant.3

“Hypoglycemia remains a dangerous risk for individuals with type 1 diabetes who are dependent on exogenous insulin administration,” Rickels added.3 “These findings indicate the potential for a novel cellular therapy that restores endogenous insulin secretion to improve outcomes for type 1 diabetes patients who have been struggling to achieve glycemic control.”

REFERENCES

1. Rickels MR, Witkowski P, Reichman TW, et al. 140-OR - Durable Glycemic Control and Elimination of Exogenous Insulin Use with VX-880 in Patients with Type 1 Diabetes (T1D)—VX-880-101 (FORWARD). Presented at ADA 2025; June 20-23; Chicago, Illinois. Presentation #140-OR

2. Reichman TW, Markmann JF, Odorico J , et al. Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes. N Eng J Med. Published online June 20, 2025.

3. Stem Cell-Derived Islet Therapies Shown to Reduce the Need for Injectable Insulin. News release. ADA. June 20, 2025.

4. Vertex Presents Positive Data for Zimislecel in Type 1 Diabetes at the American Diabetes Association 85th Scientific Sessions. News release. Vertex Pharmaceuticals. June 20, 2025. https://news.vrtx.com/news-releases/news-release-details/vertex-presents-positive-data-zimislecel-type-1-diabetes