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Phase 1/2TerminatedNCT05791201

VX-264: encapsulated stem-cell islets without immunosuppression

A Phase 1/2 trial of Vertex's stem-cell-derived islets sealed inside an immune-protective device, aiming to restore insulin production without lifelong immunosuppression. In March 2025 Vertex reported the device was safe but did not raise C-peptide enough to help, and discontinued the program.

Primary endpoints

  • Safety and tolerability: number of participants with adverse events and serious adverse events (Day 1 through 24 months)
  • Change in peak C-peptide during a mixed-meal tolerance test (MMTT), from baseline to Day 90 (Part B)

Results so far

In March 2025 Vertex reported that VX-264 was generally safe and well tolerated, but the study did not meet its efficacy endpoint: increases in C-peptide (a marker of the body's own insulin production) were not seen at the levels needed to deliver benefit. Vertex announced the program would not advance further and said it would analyze explanted devices to understand why. No detailed per-participant numbers were published.

The full picture

What this trial tested and why it matters

VX-264 set out to answer one of the most important questions in the search for a type 1 diabetes (T1D) cure: can lab-grown insulin-producing cells be protected from the immune system without the powerful anti-rejection drugs that today's cell therapies require?1 It used the same stem-cell-derived, fully differentiated islet cells as Vertex's VX-880 (zimislecel) program — but instead of infusing them into the liver with chronic immunosuppression, the cells were sealed inside a proprietary immunoprotective "channel array" device and surgically implanted.12 The device is meant to let glucose, oxygen, and insulin pass through while shielding the cells from immune attack, so recipients would not need lifelong immunosuppressant drugs.12

If it worked, this would be the "holy grail" version of a cell cure: durable insulin production with none of the infection and cancer risks that come with suppressing the immune system.3

Who it was for and how it was designed

This was an open-label Phase 1/2 study (NCT05791201) in adults aged 18–65 who had lived with T1D for at least 5 years, were on stable treatment, and used a CGM.4 It enrolled a small safety-first cohort — 7 participants in the reported analysis — across roughly 16 sites in the United States, Canada, the United Kingdom, Germany, Italy, the Netherlands, and Switzerland.4 Dosing was staggered: lower-dose groups (Part A) before full-dose groups (Part B), with the two co-primary endpoints being safety and the change in peak C-peptide (a marker of the body's own insulin production) during a mixed-meal test at Day 90.4 The first participant was dosed in 2023.2

The key result

In a portfolio update on 28 March 2025, Vertex reported that VX-264 was generally safe and well tolerated, but the study did not meet its efficacy endpoint: the increases in C-peptide "were not observed at levels necessary to deliver benefit."53 In other words, the encapsulated cells survived the procedure safely but did not produce enough insulin to help. Vertex announced the program would not advance and said it would analyze the explanted devices to understand why.53

What it means and what's next

The encapsulation strategy did not clear the bar this time — likely because sealing cells away from blood vessels also starves them of the oxygen and nutrients they need to thrive.3 Importantly, the cells themselves remain validated: the non-encapsulated version (zimislecel) has restored insulin independence in other Vertex trials, and the field's "next frontier" is still finding a way to protect islet cells without chronic immunosuppression.6 VX-264's negative result is a real data point steering that search toward better device oxygenation and alternative immune-evasion approaches.6

References

  1. Vertex Pharmaceuticals. Vertex Doses First Patient in Phase 1/2 Trial of VX-264 in Type 1 Diabetes (coverage). CGTLive (2023). https://www.cgtlive.com/view/vertex-doses-first-patient-phase-1-2-trial-vx-264-type-1-diabetes ↩ ↩2 ↩3

  2. CGTLive. Vertex Doses First Patient in Phase 1/2 Trial of VX-264 in Type 1 Diabetes. CGTLive (2023). https://www.cgtlive.com/view/vertex-doses-first-patient-phase-1-2-trial-vx-264-type-1-diabetes ↩ ↩2 ↩3

  3. Masson G. Vertex drops cell-device diabetes combo over poor phase 1 results. Fierce Biotech (2025). https://www.fiercebiotech.com/biotech/vertex-abandons-islet-cell-device-combo-after-it-failed-improve-diabetes-biomarker ↩ ↩2 ↩3 ↩4

  4. ClinicalTrials.gov. A Study to Evaluate the Safety, Tolerability, and Efficacy of VX-264 in Subjects With Type 1 Diabetes Mellitus (NCT05791201). U.S. National Library of Medicine (accessed 2026). https://clinicaltrials.gov/study/NCT05791201 ↩ ↩2 ↩3

  5. Vertex Pharmaceuticals. Vertex Announces Program Updates for Type 1 Diabetes Portfolio. Vertex Pharmaceuticals (2025). https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-program-updates-type-1-diabetes-portfolio ↩ ↩2

  6. Hering BJ, Rickels MR, Bellin MD, et al. Advances in Cell Replacement Therapies for Diabetes. Diabetes 74(7):1068-1077 (2025). https://doi.org/10.2337/db25-0037 ↩ ↩2