FORWARD: VX-880 Could Eliminate Need for Insulin in Patients with Type 1 Diabetes

Piotr Witkowski, MD, PhD

Credit: UChicago Medicine

New data from the phase 1/2 FORWARD clinical study of VX-880 islet cell therapy are highlighting its ability to reduce or eliminate the need for insulin use in patients with type 1 diabetes.¹

Findings were presented at the American Diabetes Association (ADA) 84th Scientific Sessions and showed patients experienced insulin independence and elimination of severe hypoglycemic events with VX-880, suggesting stem cell-derived islets can restore physiological islet function and glycemic control.¹

“This positive data adds to the growing body of evidence for VX-880’s potential to revolutionize the treatment of type 1 diabetes that would give patients an alternative solution other than exogenously administered insulin,” said Piotr Witkowski, MD, PhD, professor of surgery and director of the pancreatic and islet transplant program at the University of Chicago.¹ “These findings will also support further evaluation of VX-880, and we hope to see this treatment become a pivotal development in type 1 diabetes care.”

An investigational, allogeneic, stem cell-derived, fully differentiated insulin-producing islet cell therapy, VX-880 is thought to have the potential to restore the body’s ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose-responsive insulin production. It is delivered by an infusion into the hepatic portal vein and requires chronic immunosuppressive therapy to protect the islet cells from immune rejection. In March of 2021, the US Food and Drug Administration granted VX-880 Fast Track Designation.^1,2,3

The phase 1/2, open-label 3-part FORWARD study enrolled adults with type 1 diabetes, impaired hypoglycemic awareness, and ≥ 2 severe hypoglycemic events in the year before screening. The mean age of study participants was approximately 44 years, the mean HbA1c was 7.8%, and total daily insulin use was approximately 40 units per day. Among the study cohort, patients had experienced between 2-4 severe hypoglycemic events in the year prior to screening, and all participants had undetectable C-peptide at baseline.¹

Findings from the first 2 parts of the trial were presented at the 2023 Annual Meeting of the European Association for the Study of Diabetes (EASD) and showed all 6 patients treated with VX-880 experienced an improvement in glycemic control and a significant reduction in their externally administered insulin needs.⁴ Results presented at ADA showed participants who received a full dose of VX-880 as a single infusion demonstrated engraftment of islet cells and endogenous insulin (C-peptide) production, eliminated severe hypoglycemic events, and significantly improved glycemic control while simultaneously reducing or eliminating insulin use. All 12 participants achieved a reduction in HbA1c to <7.0% and a time in target range of >70%.¹

Of the 10 participants who completed the day 180 visit, 7 are no longer using exogenous insulin and 2 had approximately 70% reduction in their daily insulin use. Of note, 100% of patients with > 1 year of follow-up met the criteria for the primary endpoint of eliminating severe hypoglycemic events with HbA1c <7.0% at month 12 and achieved the secondary endpoint of insulin independence, suggesting VX-880 stem cell-derived islets function like bona fide islets.¹

The trial has been further expanded to enroll a total of approximately 37 participants in order to generate clinical data supporting VX-880’s availability for people living with type 1 diabetes in the future.¹

References:

1. ^{American Diabetes Association. Expanded FORWARD Trial Demonstrates Continued Potential for Stem Cell-Derived Islet Cell Therapy to Eliminate Need for Insulin for People with T1D. June 21, 2024. Accessed June 21, 2024.}
2. ^{Vertex. Vertex Presents Positive, Updated VX-880 Results From Ongoing Phase 1/2 Study in Type 1 Diabetes at the European Association for the Study of Diabetes 59th Annual Meeting. October 3, 2023. Accessed June 21, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-presents-positive-updated-vx-880-results-ongoing-phase-12}
3. ^{Vertex. Vertex Announces FDA Fast Track Designation and Initiation of a Phase 1/2 Clinical Trial for VX-880, a Novel Investigational Cell Therapy for the Treatment of Type 1 Diabetes. March 10, 2021. Accessed June 21, 2024. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-fda-fast-track-designation-and-initiation-phase}
4. ^{Iapoce, C. Stem Cell-Derived Therapy Improves Glucose Control in Type 1 Diabetes. HCPLive. October 4, 2023. Accessed June 21, 2024. https://www.hcplive.com/view/stem-cell-derived-therapy-improves-glucose-control-type-1-diabetes}