A stem cell–derived islet cell therapy enabled insulin independence, restored endogenous insulin production, and eliminated severe hypoglycemia in patients with type 1 diabetes, based on interim data presented at the American Diabetes Association’s 85th Scientific Sessions.
The investigational product, zimislecel, is made from allogeneic pluripotent stem cells that are differentiated into fully functional pancreatic islets. In the phase 1–2 study, zimislecel was infused into the portal vein of participants with long-standing type 1 diabetes, impaired hypoglycemia awareness, and a history of severe hypoglycemic events despite optimal medical care.
Fourteen participants received the therapy—2 at a half dose and 12 at a full dose. All were given glucocorticoid-free immunosuppressive therapy. Patients who received a half-dose had an option of receiving a second half-dose within 2 years. The study assessed safety, prevention of severe hypoglycemia from day 90 to day 365 postinfusion, and improvement in hemoglobin A1c.
At baseline, participants had undetectable C-peptide levels, which indicated an absence of endogenous insulin production. After treatment, all developed measurable C-peptide, which confirmed successful islet engraftment and insulin secretion. In the full-dose group, mean stimulated C-peptide rose to 1274 pmol/L by day 365.
Glycemic control improved across the cohort. No participant had an A1c below 7% at baseline (mean = 7.8%). By day 120, all full-dose participants achieved A1c levels below 7%. This level was maintained through 1 year, with an average reduction of 1.81 percentage points.
Continuous glucose monitoring showed an increase in time spent in the target glucose range (70–180 mg/dL) from 49.5% at baseline to 93.3% at day 365. Glucose variability also decreased over the year, as did the coefficient of variation, which dropped from 36.3% to 20%.
Ten of the 12 full-dose participants (83%) achieved insulin independence by 1 year. In these patients, the authors noted, "insulin therapy ended as early as day 150 and did not resume through day 365." The 2 remaining participants, who had received high-dose glucocorticoids around the time of infusion—against protocol—had insulin reductions of 70% and 36%, respectively. "High-dose glucocorticoid use during the periinfusion period, along with resulting glucotoxicity (impaired beta-cell function during periods of high glucose levels), may have adversely affected islet engraftment, islet survival, or both in these participants," the authors wrote.
No severe hypoglycemic events were reported in the full-dose group between day 90 and day 365. The most common adverse events were mild to moderate, including diarrhea (79%), headache (71%), and nausea (64%). Serious neutropenia occurred in 3 participants, and acute kidney injury in 2. Two deaths occurred: 1 from fungal meningitis in a participant who was exposed to prohibited glucocorticoids, and 1 from progression of preexisting neurocognitive impairment. Most serious events were linked to immunosuppressive therapy, rather than zimislecel itself.
These interim findings support continued evaluation of zimislecel as a potential beta-cell replacement strategy for type 1 diabetes. The therapy’s effects on restoring insulin secretion and reducing insulin dependence were highlighted during a presentation at the ADA’s 85th Scientific Sessions. Long-term results from the ongoing 5-year study and upcoming phase 3 trials will further assess safety, durability, and generalizability of this stem cell–based approach.
Full disclosures can be found in the published study.