Key takeaways:
- Zimislecel is an investigational stem cell-derived islet remedy for sort 1 diabetes.
- Ten of 12 contributors not required insulin at 1 yr.
- Outcomes from this section 1/2 research help additional investigation.
CHICAGO — A single infusion of zimislecel, an investigational stem cell-based remedy, restored physiologic islet perform and conferred improved outcomes and insulin independence at 1 yr in a small research of sufferers with sort 1 diabetes.
Outcomes from the section 1/2 portion of the FORWARD-101 trial, which enrolled sufferers with sort 1 diabetes with extreme hypoglycemic occasions and impaired hypoglycemic consciousness, have been offered on the American Diabetes Affiliation Scientific Periods and concurrently revealed in The New England Journal of Drugs. The trial, which had three elements, checked out security and efficacy of a single infusion of zimislecel (Vertex Prescription drugs) throughout 1 yr of follow-up.
Zimislecel improved glycemic management and restored physiologic islet perform in a small group of individuals with sort 1diabetes with extreme hypoglycemic occasions and impaired hypoglycemic consciousness. Picture: Adobe Inventory
“Zimislecel is an islet cell remedy in scientific growth for people with sort 1 diabetes difficult by recurrent extreme hypoglycemia. Zimislecel is an investigational allogeneic stem cell-derived, totally differentiated, insulin-producing islet cell remedy that’s delivered by infusion into the portal vein for intrahepatic engraftment below an immunosuppressive technique,” 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 Ailments at College of Pennsylvania Perelman Faculty of Drugs, stated throughout the presentation.
Zimislecel has the potential to revive the physique’s capacity to control glucose ranges by restoring pancreatic islet cell perform, together with glucose-responsive insulin manufacturing, in keeping with a press launch from Vertex.
Outcomes
Remedy was administered to a particular affected person inhabitants: adults with longstanding sort 1 diabetes (imply age, 42 years; largely males; all white; imply length of diabetes, 22 years); at the least two extreme hypoglycemic occasions within the prior yr; insulin dependence for at the least 5 years; baseline HbA1c higher than 7%; undetectable ranges of C-peptide at baseline; and impaired consciousness of hypoglycemia, which was outlined as incapacity to understand the onset of hypoglycemia. All contributors had acquired “applicable diabetes care” and have been utilizing steady glucose monitoring earlier than enrollment; 50% have been utilizing an automatic insulin supply system.
Members acquired both a half dose (0.4 x 109 cells) or a full dose of zimislecel, administered along with glucocorticoid-free immunosuppressive remedy.
In accordance with outcomes offered right here, after zimislecel infusion, all 12 contributors:
- demonstrated engraftment and islet perform, with glucose-responsive endogenous C-peptide manufacturing, by 1 yr of follow-up;
- achieved a goal HbA1c lower than 7% and spent greater than 70% of the time within the goal glucose vary of 70 mg/dL to 180 mg/dL;
- have been free from extreme hypoglycemic occasions from day 90 by 1 yr;
- decreased their exogenous insulin use (imply discount in each day dose: 92%), with 10 of 12 contributors (83%) not requiring exogenous insulin at 1 yr; and
- achieved the section 1/2 major endpoint of elimination of extreme hypoglycemic occasions with an HbA1c lower than 7%.
Michael R. Rickels
“Directed differentiation of pluripotent stem cells into specialised cell varieties can probably present an inexhaustible provide of substitute tissues for severe illnesses. Our research confirmed that stem cell-derived islets engrafted, produced exogenous insulin and restored the physiologic perform of islets, resulting in improved glycemic management, elimination of extreme hypoglycemic occasions and insulin independence in individuals with sort 1 diabetes,” the researchers wrote in NEJM.
Zimislecel was nicely tolerated and no severe adversarial occasions associated to zimislecel remedy occurred throughout follow-up, in keeping with the researchers. The most typical adversarial occasions have been diarrhea, headache and nausea, Rickels stated. Neutropenia, transient elevations in liver aminotransferase ranges and decreased renal perform have been additionally noticed. Two sufferers died from causes unrelated to remedy with zimislecel. The security profile is in keeping with immunosuppression, the infusion process and issues from longstanding diabetes, in keeping with the discharge from Vertex.
‘Reworking sort 1 diabetes care’
“Stem cell remedy is displaying super promise in reworking sort 1 diabetes care, providing actual hope for insulin independence,” Marlon Pragnell, PhD, ADA vice chairman of analysis and science, stated in an ADA press launch.
These outcomes “help additional investigation of zimislecel in bigger, longer research involving numerous populations,” the researchers wrote in NEJM.
FORWARD-101 is an ongoing, open-label, 5-year research.
“The section 3 research is now nicely underway and is predicted to finish enrollment of roughly 50 … people by the tip of the summer season,” Rickels stated.
References:
Sources/Disclosures
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Rickels M. 140-OR. Offered at: American Diabetes Affiliation Scientific Periods; June 20-23, 2025; Chicago.
Disclosures:
Pragnell is vice chairman of analysis and science on the ADA. Rickels stories consulting for Novo Nordisk and Vertex Prescription drugs and receiving analysis help from Dompé and Tandem Diabetes Care. Please see the research for all different authors’ related monetary disclosures.
