ZIMISLECEL, a new allogeneic stem cell-derived islet cell therapy, has shown promise in a recent study involving people with Type 1 diabetes. The condition, marked by autoimmune destruction of insulin-producing beta cells, typically requires lifelong insulin therapy and carries a risk of severe hypoglycaemia. A recent early-stage trial aimed to assess the safety and efficacy of zimislecel in restoring islet function in affected individuals. A key finding was that 83% of participants treated with the full dose no longer required insulin after one year.
This phase 1–2 clinical trial separated participants into three groups. In part A, two individuals received a half dose (0.4×10⁹ cells) of zimislecel, with an option for a second dose within two years. In parts B and C, 12 participants received a single full dose (0.8×10⁹ cells). All participants were given glucocorticoid-free immunosuppressive therapy. The primary outcome for part C was defined as the absence of severe hypoglycaemic events between days 90 and 365, with concurrent improvement in HbA1c to below 7% or a reduction of at least one percentage point from baseline between days 180 and 365. C-peptide levels were measured to assess islet function and engraftment.
All 14 participants, who had no detectable C-peptide at baseline, showed evidence of islet engraftment and function post-treatment. Among those who received the full dose, 100% remained free of severe hypoglycaemic events and achieved HbA1c targets, spending over 70% of their time in the optimal glucose range (70–180 mg/dL). Furthermore, 10 of 12 participants (83%) achieved insulin independence at one year. However, neutropenia was the most common serious adverse event, affecting three participants. Two deaths occurred during the study: one due to cryptococcal meningitis and another linked to severe pre-existing neurocognitive decline.
While the findings are encouraging, the study’s small sample size and short follow-up duration limit generalisability. The results suggest that zimislecel has the potential to transform treatment in Type 1 diabetes by restoring islet function, but further larger scale, longer term trials are needed. Clinicians should remain cautious but alert to future developments that could redefine insulin management in this patient group.
Reference
Reichman TW et al. Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes. N Engl J Med. 2025;DOI: 10.1056/NEJMoa2506549.
