Vertex Showcases Groundbreaking Data for Zimislecel in Type 1 Diabetes at ADA 85th Scientific Sessions
Vertex Pharmaceuticals Incorporated has announced compelling new clinical data from its ongoing FORWARD-101 trial, underscoring the transformative potential of its investigational islet cell therapy, zimislecel (VX-880), in patients with type 1 diabetes (T1D). The updated data, drawn from the Phase 1/2 segment of the larger Phase 1/2/3 FORWARD-101 clinical program, were unveiled during a high-profile oral presentation at the 85th Scientific Sessions of the American Diabetes Association (ADA) held in Chicago. The results were also simultaneously published in the New England Journal of Medicine, marking a significant milestone in the development of a new therapeutic modality aimed at addressing one of the most challenging forms of diabetes.
Background: Addressing a High-Risk Subset of T1D
Type 1 diabetes is a chronic autoimmune condition in which the body’s immune system attacks and destroys insulin-producing beta cells in the pancreas. Individuals with T1D must rely on lifelong insulin therapy to regulate blood glucose levels. For some, however, disease management becomes even more precarious due to impaired hypoglycemia awareness and a heightened risk of severe hypoglycemic events (SHEs). These episodes can lead to confusion, unconsciousness, and even death, posing significant risks to patients’ quality of life and safety.
Zimislecel, Vertex’s investigational product, is a stem cell-derived, fully differentiated islet cell therapy designed to replace the function of the damaged pancreatic beta cells in individuals with T1D. The therapy is manufactured as an “off-the-shelf” solution, meaning that the cells are derived and processed in advance from pluripotent stem cells and then administered as a single infusion into patients. Unlike autologous or donor-derived islet transplants, zimislecel offers the potential for scalable and consistent manufacturing, removing the limitations associated with organ availability or donor compatibility.
Summary of the New Data: One-Year Follow-Up in 12 Patients
The most recent dataset focuses on 12 patients enrolled in the FORWARD-101 trial who received the full target dose of zimislecel through a single infusion. As of the data cutoff in October 2024, each of these participants had completed at least 12 months of follow-up. The outcomes presented by Vertex demonstrate strong and durable clinical efficacy, paired with a favorable safety profile.
All 12 patients demonstrated successful engraftment of the transplanted islet cells, evidenced by glucose-responsive production of endogenous C-peptide. C-peptide is a biomarker that indicates the presence of functional beta cell activity, suggesting that zimislecel successfully restored the body’s intrinsic ability to produce insulin. Importantly, this endogenous insulin production remained consistent throughout the one-year period, reinforcing the durability of the therapeutic effect.
Crucially, all participants achieved the American Diabetes Association’s key targets for glycemic control: hemoglobin A1c (HbA1c) levels below 7% and more than 70% of their time spent within the recommended blood glucose range. These metrics are widely accepted indicators of well-controlled diabetes and are directly associated with reduced risk of long-term complications.
Another highlight of the findings is the profound impact on patients’ reliance on externally administered insulin. On average, patients experienced a 92% reduction in their daily exogenous insulin requirements. Even more striking, 10 out of the 12 participants — equivalent to 83% — were completely insulin-independent at the 12-month mark.
Perhaps most importantly for this high-risk population, all 12 participants were free of severe hypoglycemic events from 90 days post-infusion through the end of the one-year follow-up period. The elimination of SHEs — combined with improved glycemic control and insulin independence — marks the successful achievement of the trial’s primary Phase 1/2 endpoint.
Safety Profile: Generally Well Tolerated
Vertex also reported encouraging safety outcomes. Zimislecel was generally well tolerated, with most adverse events categorized as mild to moderate. No serious adverse events were attributed to the treatment itself. The safety profile was consistent with what would be expected from the immunosuppressive regimen used in the study, the infusion process, and the complications typically associated with long-standing type 1 diabetes.
Two patient deaths were reported during the study period, but both were determined to be unrelated to zimislecel therapy. The company emphasized that these unfortunate events do not reflect safety concerns specific to the investigational product, and the overall safety data support continued development of the therapy.
Expert Commentary: Optimism from Clinical and Scientific Leaders
Vertex executives and investigators involved in the trial expressed strong optimism regarding the potential of zimislecel to dramatically reshape the treatment paradigm for people living with type 1 diabetes — particularly those facing the greatest clinical challenges.
“These data on the first fully differentiated, stem cell-derived, off-the-shelf islet cell therapy continue to be unprecedented,” said Dr. Carmen Bozic, Executive Vice President of Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex. “The magnitude, consistency, and durability of the results from all 12 patients with more than one year of follow-up reinforce the transformative potential of zimislecel for people living with T1D complicated by severe hypoglycemia. We are excited to complete enrollment and dosing in the Phase 1/2/3 Program and look forward to potential regulatory submissions next year.”
The presentation at the ADA meeting was delivered by Dr. Michael R. Rickels, M.D., M.S., Medical Director of the Pancreatic Islet Cell Transplant Program at the University of Pennsylvania and a leading authority in diabetes research. Dr. Rickels also serves as a steering committee co-chair for the zimislecel clinical program and is the lead author on the corresponding New England Journal of Medicine publication.
Reflecting on the data, Dr. Rickels noted: “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. 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.”
Toward Regulatory Submission and Broader Impact
With these latest findings, Vertex is now preparing to complete the Phase 1/2/3 clinical program and is setting its sights on future regulatory submissions. If approved, zimislecel could become the first-ever stem cell-derived islet cell therapy to reach the market for type 1 diabetes, offering a potentially curative approach for patients who struggle to achieve adequate glycemic control with current treatments.
Beyond the clear clinical benefits demonstrated thus far, zimislecel represents a broader shift in the therapeutic landscape — one that leverages regenerative medicine, cellular engineering, and stem cell science to solve previously intractable medical challenges. Vertex’s pioneering efforts in this space signal a future in which chronic diseases like type 1 diabetes can be fundamentally reimagined and potentially reversed.
For now, the diabetes and scientific communities will be closely watching the continued progress of zimislecel and the upcoming developments from Vertex’s broader cell and genetic therapy portfolio.
