A stem cell-derived islet therapy has demonstrated the potential to eliminate severe hypoglycemic episodes and reduce insulin dependence in patients with type 1 diabetes, according to results from a phase 1-2 clinical trial presented at the American Diabetes Association’s 85th Scientific Sessions and published simultaneously in the NEJM.
The study evaluated VX-880 (zimislecel), an experimental treatment composed of stem cell-derived pancreatic islet cells that can produce insulin. Among the 12 patients who received the full dose and completed one year of follow-up, all achieved target blood sugar control and were free from severe hypoglycemic episodes, and 10 patients (83%) no longer required insulin injections.
Challenges in Type 1 Diabetes
Patients with type 1 diabetes require lifelong insulin therapy, but achieving optimal glucose control remains challenging. Michael Rickels, MD, of the University of Pennsylvania Perelman School of Medicine, who presented the study findings at the meeting, explained that the narrow therapeutic window for insulin creates a constant balancing act between preventing high blood sugar and avoiding dangerous hypoglycemic episodes. He noted that despite therapeutic advances in type 1 diabetes, the available treatment options have a high treatment burden and do not always achieve physiological glucose regulation.
Study Design
The VX-880-101 FORWARD trial enrolled adults with type 1 diabetes who had impaired hypoglycemia awareness and at least two severe hypoglycemic episodes in the previous year. All participants received appropriate diabetes care, including continuous glucose monitoring, and 50% were using automated insulin delivery systems. Patients received a single infusion of VX-880 cells directly into the portal vein, along with immunosuppressive therapy to prevent rejection.
Key Findings
All 12 participants achieved hemoglobin A1c levels below 7% by day 120, with a mean reduction of 1.81 percentage points at one year. Time spent in target glucose range (70-180 mg/dL) improved from a baseline average of 49.5% to 93.3% at one year. Mean insulin dose decreased by 92%, with 10 patients achieving complete insulin independence. Two participants who continued to require insulin had received high-dose glucocorticoids shortly after treatment, which may have impaired islet engraftment. Even these patients experienced reductions in insulin dose of 36% and 70%, respectively. No severe hypoglycemic episodes occurred from day 90 onward.
Dr. Rickels emphasized the potential curative effects of the treatment. These durable clinical benefits of VX-880, including the elimination of severe hypoglycemic episodes, improved glycemic control, and freedom from exogenous insulin, support the curative potential of VX-880, he noted in his presentation.
Safety Profile
Most adverse events were mild to moderate in severity and consistent with the immunosuppressive regimen. Common side effects included diarrhea, headache, nausea, neutropenia, and rash. Two deaths occurred during the study period, but investigators determined that neither was related to the experimental therapy.
Three patients experienced serious neutropenia requiring hospitalization for observation, and two had acute kidney injury. Dr. Rickels noted that the safety profile aligned with expectations for islet transplantation procedures and immunosuppressive protocols.
Clinical Significance and Future Directions
Dr. Rickels emphasized that VX-880, the first and only allogeneic, stem cell-derived, islet cell therapy in pivotal development, has demonstrated durable clinical benefits with curative potential. He explained that this is a significant advancement in beta-cell replacement therapy, as stem cell-derived islets could provide an unlimited supply of replacement tissue, in contrast to traditional islet transplantation, which is limited by organ availability and variable quality.
The study’s interim results support the advancement of VX-880 to larger, longer-term trials. The phase 3 portion of the FORWARD study is currently ongoing, and participants will be followed for five years with an additional five-year extension study.
Dr. Evangelou has no conflicts of interest to report.
Image by pinkeyes / Shutterstock
