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Phase 3RecruitingNCT04786262

VX-880 / zimislecel: stem-cell-derived islets (with immunosuppression)

Vertex's pluripotent-stem-cell-derived islet cell therapy infused into the liver, with lifelong immunosuppression. In the published Phase 1/2 results, 10 of 12 fully dosed patients (83%) became insulin-independent at one year and all eliminated severe hypoglycemia with HbA1c under 7%. Now in a pivotal Phase 3 (FORWARD), with regulatory submissions targeted for 2026. The leading cell-replacement cure candidate.

Primary endpoints

  • Part A: Safety and tolerability (number of participants with adverse events) through end of study (up to 5 years)
  • Parts B and C: Proportion of participants who are insulin-independent with absence of severe hypoglycemic events at 1 year after achieving insulin independence
  • Published Part C primary endpoint: freedom from severe hypoglycemic events during days 90-365 with HbA1c <7% or a reduction of at least 1 percentage point from baseline at one or more time points between days 180-365

Results so far

In the published interim Phase 1/2 analysis, all 14 followed participants (who had no detectable C-peptide at baseline) showed engraftment and restored insulin production after infusion. Among the 12 who received a full single dose, all 12 were free of severe hypoglycemic events with HbA1c under 7% and spent more than 70% of time in the target glucose range; 10 of 12 (83%) were completely off injected insulin at day 365, with a mean ~92% reduction in insulin use across the group. The most common serious adverse event was neutropenia (3 participants). Two deaths occurred, judged unrelated to the therapy (one from cryptococcal meningitis, one from progression of pre-existing dementia).

The full picture

What is being tested, and why it matters

Type 1 diabetes destroys the insulin-producing islet cells of the pancreas, leaving people dependent on injected insulin for life. Zimislecel (formerly VX-880) is an attempt to replace those lost cells. Vertex grows fully working islet cells from pluripotent stem cells in the lab, then infuses them as a single dose into the liver's main blood vessel, where they engraft and start making insulin in response to blood sugar.1 Because the cells come from a donor cell line rather than the patient, recipients also take immune-suppressing drugs to stop rejection.1 This is the leading "cell-replacement cure" candidate: an off-the-shelf source of islets, in contrast to therapies that rely on scarce deceased-donor pancreases.2

Who it is for

The trial enrolls adults aged 18-65 who have had type 1 diabetes for more than five years, who can no longer feel their lows coming (impaired hypoglycemic awareness), and who have had repeated severe hypoglycemic events.3 These are people for whom dangerous, sometimes life-threatening lows are a constant risk.

How the study is designed

NCT04786262 ("FORWARD") is a single-group, open-label Phase 1/2/3 study sponsored by Vertex, now in its pivotal Phase 3 stage with about 52 participants planned across roughly 29 sites in the US, Canada, the UK, and Europe.3 Part A tested a half dose and tracked safety; Parts B and C use a full single dose, with the key efficacy measure being freedom from severe lows at one year combined with an HbA1c under 7%.3 The study began in 2021 and is expected to run, with follow-up, into 2030.3

Key results so far

The published interim Phase 1/2 results are striking. All 14 patients analyzed had no detectable insulin production at the start, and every one began producing insulin after infusion.1 Among the 12 who received a full single dose, all 12 were free of severe hypoglycemic events and had an HbA1c below 7%, spending more than 70% of the day in the target glucose range.1 Ten of the 12 (83%) were completely off injected insulin at one year,1 with a roughly 92% average reduction in insulin use across the group.2 The most common serious side effect was low white-blood-cell counts (3 patients); two deaths occurred but were judged unrelated to the therapy.1

What it means and what is next

These results support the idea that lab-grown islets can restore the body's own insulin control.1 Vertex aimed to finish enrolling and dosing the ~50-patient Phase 3 group in 2025 and to file for approval with the FDA, EMA, and UK MHRA in 2026.2 The major remaining caveat is the need for lifelong immunosuppression; separate Vertex programs aim to remove that requirement.4

References

  1. Reichman TW, Markmann JF, Odorico J, et al. Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes. N Engl J Med (2025);393(9):858-868. According to PubMed. https://doi.org/10.1056/NEJMoa2506549 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  2. Vinluan F. Vertex Pharma's Type 1 Diabetes Cell Therapy Shows Potential to Achieve Insulin Independence. MedCity News (2025). https://medcitynews.com/2025/06/vertex-pharmaceuticals-type-1-diabetes-cell-therapy-zimislecel-insulin-vrtx/ ↩ ↩2 ↩3

  3. A Study to Evaluate the Safety, Tolerability, and Efficacy of VX-880 in Participants With Type 1 Diabetes (FORWARD). ClinicalTrials.gov, NCT04786262 (accessed 2026). https://clinicaltrials.gov/study/NCT04786262 ↩ ↩2 ↩3 ↩4

  4. Vertex's Islet Cell Therapy Zimislecel (VX-880) Restores Endogenous Insulin Secretion in Type 1 Diabetes. CGTlive (2025). https://www.cgtlive.com/view/vertex-islet-cell-therapy-vx-880-restores-endogenous-insulin-secretion-type-1-diabetes ↩