FORWARD: Zimislecel Relieves Insulin Dependence in Patients with T1D with Michiel Nijhoff, MD

The FORWARD trial has shown that zimislecel (VX-880) led to meaningful continuous glucose monitor (CGM) metric improvements and reduced insulin dependence in patients with type 1 diabetes (T1D) with impaired hypoglycemic awareness and severe hypoglycemic events (SHEs).1

Presented at the 61st Annual Meeting of the European Association for the Study of Diabetes (EASD) by Michiel Nijhoff, MD, an internist/endocrinologist at the Leiden University Medical Center, these data showcase zimislecel’s ability to minimize glycemic variability and optimize time in range (TIR).1

Zimislecel is an investigative allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy, made by parent company Vertex Therapeutics via proprietary technology. The drug has the potential to restore an individual’s ability to regulate glucose levels by restoring function to pancreatic islet cells, such as glucose-responsive insulin production. Delivered by an infusion into the hepatic portal vein, zimislecel requires chronic immunosuppressive therapy to prevent immune rejection of the islet cells.2

The editorial team at HCPLive sat down with Nijhoff to discuss his findings and the potential path forward for this revolutionary therapy.

“People with [T1D] live 10 years shorter than people without,” Nijhoff told HCPLive. “They get heart disease, they get eye disease, kidney disease, and nerve disease. Despite everything we do now, it’s not enough. So that’s the idea of the cell transplant – to cure the diabetes and actually stop this process.”

FORWARD is an ongoing phase 1/2/3 study; the phase 1/2 portion has been completed, resulting in these data. A total of 12 patients had completed the study at time of reporting, all of whom received a full dose of zimislecel as a single infusion and were followed for ≥1 year. Included patients were required to have a clinical history of T1D with >5 years of duration of insulin dependence, ≥2 documented episodes of severe hypoglycemia in the 12 months prior to enrollment, stable diabetic treatment, and consistent use of CGM for ≥3 months before screening.2,3

All 12 included participants demonstrated engraftment with glucose-responsive endogenous C-peptide production, which was durable through 1 year of follow-up. Additionally, these patients achieved the ADA targets of HbA1c <7% and TIR of >70%, were free of SHEs from day 90, and had a reduction in exogenous insulin use – the mean of which was 92%. 10 of 12 patients no longer required exogenous insulin at month 12; the remaining 2 were able to significantly reduce and simplify their insulin regimen.2

Zimislecel’s safety profile was also consistent with the immunosuppressive regimen and the infusion procedure. The majority of adverse events were mild or moderate; those with a causal relationship to the study drug were mostly attributed to immunosuppressive therapy. No severe adverse events were considered related to zimislecel, nor were the 2 deaths occurring during the trial.1

Nijhoff also spoke on the next steps for zimislecel, including what key aspects investigators will be monitoring during future trials.

“What’s important for the future is the durability of these cells – how long does this effect stay, and if there is attrition to the function, what kind of attrition do we see?” Nijhoff said. “Is it quick or very slow? Is it related to the medication, or could we perhaps find other triggers that we could also treat somehow? Perhaps we can find what’s happening and how we can treat that, prevent it from continuing.”

References

1. Philipson L, Nijhoff M, Perkins B, et al. Achievement of Target CGM Metrics in People with T1D Treated with Zimislecel (VX-880) in the FORWARD Study. Presented at the 61st Annual Meeting of the European Association for the Study of Diabetes (EASD). Vienna, Austria. September 15-19, 2025.

2. Vertex Pharmaceuticals Incorporated. Vertex Presents Positive Data for Zimislecel in Type 1 Diabetes at the American Diabetes Association 85th Scientific Sessions. June 20, 2025. Accessed October 14, 2025. https://news.vrtx.com/news-releases/news-release-details/vertex-presents-positive-data-zimislecel-type-1-diabetes

3. Vertex Pharmaceuticals Incorporated. A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes. ClinicalTrials.gov Identifier: NCT04786262. Updated August 1, 2025. Accessed October 14, 2025. https://clinicaltrials.gov/study/NCT04786262