Katie Kalvaitis , 2025-06-21 19:11:00
Key takeaways:
- Zimislecel is an investigational stem cell-derived islet therapy for type 1 diabetes.
- Ten of 12 participants no longer required insulin at 1 year.
- Results from this phase 1/2 study support further investigation.
CHICAGO — A single infusion of zimislecel, an investigational stem cell-based therapy, restored physiologic islet function and conferred improved outcomes and insulin independence at 1 year in a small study of patients with type 1 diabetes.
Results from the phase 1/2 portion of the FORWARD-101 trial, which enrolled patients with type 1 diabetes with severe hypoglycemic events and impaired hypoglycemic awareness, were presented at the American Diabetes Association Scientific Sessions and simultaneously published in The New England Journal of Medicine. The trial, which had three parts, looked at safety and efficacy of a single infusion of zimislecel (Vertex Pharmaceuticals) during 1 year of follow-up.
Zimislecel improved glycemic control and restored physiologic islet function in a small group of people with type 1diabetes with severe hypoglycemic events and impaired hypoglycemic awareness. Image: Adobe Stock
“Zimislecel is an islet cell therapy in clinical development for individuals with type 1 diabetes complicated by recurrent severe hypoglycemia. Zimislecel is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy that is delivered by infusion into the portal vein for intrahepatic engraftment under an immunosuppressive strategy,” Michael R. Rickels, MD, MS, medical director of the Pancreatic Islet Cell Transplant Program and the Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases at University of Pennsylvania Perelman School of Medicine, said during the presentation.
Zimislecel has the potential to restore the body’s ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose-responsive insulin production, according to a press release from Vertex.
Results
Treatment was administered to a specific patient population: adults with longstanding type 1 diabetes (mean age, 42 years; mostly men; all white; mean duration of diabetes, 22 years); at least two severe hypoglycemic events in the prior year; insulin dependence for at least 5 years; baseline HbA1c greater than 7%; undetectable levels of C-peptide at baseline; and impaired awareness of hypoglycemia, which was defined as inability to perceive the onset of hypoglycemia. All participants had received “appropriate diabetes care” and were using continuous glucose monitoring before enrollment; 50% were using an automated insulin delivery system.
Participants received either a half dose (0.4 x 109 cells) or a full dose of zimislecel, administered in addition to glucocorticoid-free immunosuppressive therapy.
According to results presented here, after zimislecel infusion, all 12 participants:
- demonstrated engraftment and islet function, with glucose-responsive endogenous C-peptide production, through 1 year of follow-up;
- achieved a target HbA1c less than 7% and spent more than 70% of the time in the target glucose range of 70 mg/dL to 180 mg/dL;
- were free from severe hypoglycemic events from day 90 through 1 year;
- reduced their exogenous insulin use (mean reduction in daily dose: 92%), with 10 of 12 participants (83%) no longer requiring exogenous insulin at 1 year; and
- achieved the phase 1/2 primary endpoint of elimination of severe hypoglycemic events with an HbA1c less than 7%.
Michael R. Rickels
“Directed differentiation of pluripotent stem cells into specialized cell types can potentially provide an inexhaustible supply of replacement tissues for serious diseases. Our study showed that stem cell-derived islets engrafted, produced exogenous insulin and restored the physiologic function of islets, leading to improved glycemic control, elimination of severe hypoglycemic events and insulin independence in persons with type 1 diabetes,” the researchers wrote in NEJM.
Zimislecel was well tolerated and no serious adverse events related to zimislecel treatment occurred during follow-up, according to the researchers. The most common adverse events were diarrhea, headache and nausea, Rickels said. Neutropenia, transient elevations in liver aminotransferase levels and decreased renal function were also observed. Two patients died from causes unrelated to treatment with zimislecel. The safety profile is consistent with immunosuppression, the infusion procedure and complications from longstanding diabetes, according to the release from Vertex.
‘Transforming type 1 diabetes care’
“Stem cell therapy is showing tremendous promise in transforming type 1 diabetes care, offering real hope for insulin independence,” Marlon Pragnell, PhD, ADA vice president of research and science, said in an ADA press release.
These results “support further investigation of zimislecel in larger, longer studies involving diverse populations,” the researchers wrote in NEJM.
FORWARD-101 is an ongoing, open-label, 5-year study.
“The phase 3 study is now well underway and is expected to complete enrollment of approximately 50 … individuals by the end of the summer,” Rickels said.
References:
Sources/Disclosures
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Rickels M. 140-OR. Presented at: American Diabetes Association Scientific Sessions; June 20-23, 2025; Chicago.
Disclosures:
Pragnell is vice president of research and science at the ADA. Rickels reports consulting for Novo Nordisk and Vertex Pharmaceuticals and receiving research support from Dompé and Tandem Diabetes Care. Please see the study for all other authors’ relevant financial disclosures.
