Vertex’s Islet Cell Therapy Zimislecel (VX-880) Restores Endogenous Insulin Secretion in Type 1 Diabetes

Vertex Pharmaceuticals’ zimislecel (also known as VX-880), an investigational allogeneic insulin-producing islet cell therapy, has restored endogenous insulin secretion in patients with type 1 diabetes (T1D) treated in the phase 1/2 FORWARD clinical trial (NCT04786262).¹ The data were announced in an oral presentation at the 85th Scientific Sessions of the American Diabetes Association® (ADA) , held June 20 to 23, in Chicago, IL, and simultaneously reported in the New England Journal of Medicine.

Among 12 patients with T1D with impaired hypoglycemic awareness treated in FORWARD, all 12 showed restored endogenous insulin secretion, as assessed via C-peptide. Furthermore, the patients showed cessation of severe hypoglycemia events and hit recommended glycemic control targets, which constituted A1C at less than 7% and time in range of greater than 70%. Use of exogenous insulin was cut down by a mean of 92% across all patients, with 10 of the 12 patients no longer using exogenous insulin at all.

With regard to safety, adverse events (AEs) were noted to be in line with expectations for islet infusion procedures and the immunosuppressive drug regimens. There were no other AEs seen in the treated patients.

“Hypoglycemia remains a dangerous risk for individuals with T1D who are dependent on exogenous insulin administration,” investigator Michael Rickels, MD, MS, the Willard and Rhoda Ware professor in diabetes and metabolic diseases in the Division of Endocrinology, Diabetes & Metabolism, at University of Pennsylvania Perelman School of Medicine, who presented the data, said in a statement.¹ “These findings indicate the potential for a novel cellular therapy that restores endogenous insulin secretion to improve outcomes for T1D patients who have been struggling to achieve glycemic control.”

Before the end of the year, it is expected that FORWARD, which is currently in phase 3, will have finished enrollment and dosed around 50 patients. Vertex also plans to initiate a separate study that will evaluate VX-880 in 10 adult patients who have previously received a kidney transplant and are thus already receiving an immunosuppressive therapy regimen.

Notably, in January 2024, FORWARD was put on a protocol-specified pause by Vertex following 2 patient deaths that were deemed unrelated to VX-880.² The VX-880 trial had previously been placed on hold by the FDA in May 2022, after the FDA determined there was insufficient information to support dose escalation, despite an Independent Data Monitoring Committee’s recommendation to advance patients to part B of the study and full dosing.³ At the time, Carmen Bozic, MD, the executive vice president of Global Medicines Development and Medical Affairs and the chief medical officer of Vertex, expressed surprise at the FDA’s decision. The FDA later lifted the hold in July 2022.⁴

REFERENCES
1. Stem cell-derived islet therapies shown to reduce the need for injectable insulin. News release. American Diabetes Association. June 20, 2025. Accessed June 20, 2025. https://diabetes.org/newsroom/press-releases/stem-cell-derived-islet-therapies-shown-reduce-need-injectable-insulin
2. Vertex provides pipeline and business updates in advance of upcoming investor meetings. News release. January 7, 2024. Accessed June 20, 2025. https://www.businesswire.com/news/home/20240107188174/en/Vertex-Provides-Pipeline-and-Business-Updates-in-Advance-of-Upcoming-Investor-Meetings
3. Vertex provides updates on phase 1/2 clinical trial of VX-880 for the treatment of type 1 diabetes. News release. Vertex Pharmaceuticals. May 2, 2022. Accessed June 20, 2025. https://news.vrtx.com/press-release/vertex-provides-updates-phase-12-clinical-trial-vx-880-treatment-type-1-diabetes
4. Vertex announces FDA has lifted the clinical hold on VX-880 phase 1/2 clinical trial for the treatment of type 1 diabetes. News release. Vertex Pharmaceuticals. July 5, 2022. Accessed June 20, 2025. https://www.businesswire.com/news/home/20220705005299/en/Vertex-Announces-FDA-Has-Lifted-the-Clinical-Hold-on-VX-880-Phase-12-Clinical-Trial-for-the-Treatment-of-Type-1-Diabetes