zimislecel (VX-880) / Vertex - LARVOL DELTA

Stem cell derived islets for T1D; data from the FORWARD clinical trial of zimislecel' (ASGCT 2026) - "Organized by the Cell and Gene Therapies of Genetic and Metabolic Diseases Committee."

Clinical • Gene Therapies • Metabolic Disorders

ACHIEVEMENT OF TARGET CGM METRICS IN PEOPLE WITH TYPE 1 DIABETES (T1D) TREATED WITH ZIMISLECEL (VX-880) IN THE FORWARD STUDY (ATTD 2026) - "A single infusion of zimislecel resulted in reductions or elimination of insulin use, reduced HbA1c levels, and improved CGM metrics to levels that met ADA/EASD endorsed targets. These data demonstrate the transformative potential of zimislecel for people with T1D experiencing SHEs."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

DURABLE GLYCEMIC CONTROL AND ELIMINATION OF EXOGENOUS INSULIN USE WITH ZIMISLECEL (VX-880) IN PEOPLE WITH TYPE 1 DIABETES (T1D): VX-880-101 (FORWARD) (ATTD 2026) - "These durable clinical benefits support the curative potential of zimislecel, the first and only allogeneic, stem-cell derived, islet cell therapy in pivotal development."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Overview of the Major Clinical Trials Investigating Stem Cells-based Therapies for Diabetes. (PubMed, Diabetes Metab) - "Vertex's VX-880 program achieved insulin independence, and a 2024 Cell study reported the first functional cure of type 1 diabetes using chemical induced iPSCs (CiPSCs)-derived islets...Despite promising outcomes, no clinical stem cell-derived therapy is yet routine, with tumorigenicity, immune rejection, and scalability as key challenges. Future directions focus on gene-edited immune-evasive cells, advanced biomaterials, scalable bioreactors, and harmonized regulation to achieve durable insulin independence and global accessibility."

Journal • Review • Diabetes • Fibrosis • Immunology • Metabolic Disorders • Oncology • Transplantation • Type 1 Diabetes Mellitus

Stem Cell Therapy as a Regenerative Strategy in Hereditary Pancreatitis Postpancreatectomy. (PubMed, Ann Afr Med) - "These studies led to the creation of CRISPR VCTX210, VC-02 implants by ViaCyte. VX-880 by Vertex, in its phase 3 trial, used fully differentiated, allogenic pluripotent-stem-cell-derived islet therapy as a functional cure for type 1 diabetes...The enduring risk of insulin-dependent diabetes associated with HP can be mitigated through the regeneration of function with PSC-derived implants and MSC co-transplantation after pancreatectomy. Researchers may find this review useful in developing procedures for patient selection and monitoring, and clinicians may find it helpful in incorporating new treatments into patient care for HP."

Journal • Diabetes • Metabolic Disorders • Pancreatitis • Transplantation • Type 1 Diabetes Mellitus

A UK key opinion leader perspective: Navigating the immunological and logistical transformation brought by stem cell-derived islets for the treatment of type 1 diabetes. (PubMed, Diabet Med) - "Stem cell-derived islets may redefine islet transplantation for T1D by enabling more scalable, less invasive and sustainable therapeutic pathways while maintaining access to technological diabetes management options."

Journal • Review • Diabetes • Immunology • Infectious Disease • Metabolic Disorders • Oncology • Transplantation • Type 1 Diabetes Mellitus

Vertex has completed enrollment in the Phase 1/2/3 study of zimislecel in people with T1D and has temporarily postponed completion of dosing in the study, pending an ongoing internal manufacturing analysis. (Businesswire) - "Zimislecel has been granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the U.S. Food and Drug Administration, PRIME designation from the EMA, Breakthrough Medicine designation from the Kingdom of Saudi Arabia, and has secured an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA)."

European regulatory • Fast track • FDA event • Trial status • Type 1 Diabetes Mellitus

Durable glycaemic control and elimination of exogenous insulin use with VX-880 in patients with type 1 diabetes: VX-880-101 (FORWARD) (EASD 2025) - P3 | "These durable clinical benefits of VX-880 with elimination of SHEs, improved glycemic control, and freedom from exogenous insulin support the curative potential of VX-880, the first and only allogeneic, stem-cell derived, islet cell therapy in pivotal development."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Achievement of target CGM metrics in people with type 1 diabetes treated with zimislecel (VX-880) in the FORWARD study (EASD 2025) - P3 | "A single infusion of zimislecel resulted in reductions or elimination of insulin use, reduced HbA1c, and improved CGM metrics to levels above ADA/EASD endorsed targets for time-in, -below and -above range. These data demonstrate the transformative potential of zimislecel for people with T1D experiencing SHEs."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Historically Based Perspective on the Immunotherapy of Type 1 Diabetes: Where We Have Been, Where We Are, and Where We May Go. (PubMed, J Clin Med) - " Initial therapies such as corticosteroids and cyclosporine offered proof-of-concept for immune modulation, yet suffered from relapse and toxicity. The introduction of monoclonal antibodies (e.g., teplizumab) marked a shift toward immune-specific intervention, particularly in stage 2 preclinical T1DM...Cellular therapies such as Treg adoptive transfer, chimeric antigen receptor Tregs (CAR-Tregs), and stem cell-derived islet replacements (e.g., VX-880) have shown promise in preserving β-cell function and modulating autoimmunity...The convergence of targeted biologics, regenerative cell therapies, and β-cell replacement approaches, supported by AI-enabled patient stratification, offers a realistic path toward durable immune tolerance and functional β-cell preservation. Continued integration of these modalities, coupled with rigorous long-term evaluation, will be essential to transform these scientific advances into sustained clinical benefit."

Journal • Diabetes • Immune Modulation • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Stem Cell-Derived Islets FORWARD VX-880 Trial Update (ADA 2025) - No abstract available

Metabolic Disorders

Durable Glycemic Control and Elimination of Exogenous Insulin Use with VX-880 in Patients with Type 1 Diabetes (T1D)—VX-880-101 (FORWARD) (ADA 2025) - "These durable clinical benefits of VX-880 with elimination of SHEs, improved glycemic control, and freedom from exogenous insulin support the curative potential of VX-880, the first and only allogeneic, stem-cell derived, islet cell therapy in pivotal development."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes. (PubMed, N Engl J Med) - P3 | "The results of this small, short-term study involving persons with type 1 diabetes support the hypothesis that zimislecel can restore physiologic islet function, warranting further clinical investigation. (Funded by Vertex Pharmaceuticals; VX-880-101 FORWARD ClinicalTrials.gov number, NCT04786262.)."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Hematological Disorders • Hypoglycemia • Infectious Disease • Metabolic Disorders • Neutropenia • Type 1 Diabetes Mellitus

Vertex Presents Positive Data for Zimislecel in Type 1 Diabetes at the American Diabetes Association 85th Scientific Sessions (Vertex Press Release) - P1/2/3 | N=52 | FORWARD-101 (NCT04786262) | Sponsor: Vertex Pharmaceuticals Incorporated | " Vertex Pharmaceuticals Inc...announced simultaneous presentation and publication of updated data from the Phase 1/2 portion of the Phase 1/2/3 FORWARD-101 clinical trial...The data are from 12 patients who received the full dose of zimislecel as a single infusion and were followed for at least one year, as of October 2024. Results from the study to date continue to demonstrate the transformative potential of zimislecel with consistent and durable patient benefit with longer follow-up. All 12 participants: Demonstrated engraftment with glucose-responsive endogenous C-peptide production, which was durable through one year of follow-up. Achieved the ADA targets of HbA1c 70%. Were free of SHEs from day 90 onwards. Had a reduction in exogenous insulin use (mean reduction in daily insulin dose: 92%). 10/12 (83%) no longer required exogenous insulin at Month 12."

P1/2 data • Type 1 Diabetes Mellitus

SR-02, a Novel Islet Replacement Therapy for Insulin-Requiring Diabetes (ASGCT 2025) - P1/2 | "Allogeneic cadaveric islets infused to the portal hepatic circulation with concurrent immune suppression (Lantidra) and an experimental, embryonic stem cell-derived product (Zimislecel), also infused to the portal circulation with immune suppression, have both resulted in insulin independence in patients of type 1 diabetes...Omental administration and elimination of de novo systemic immune suppression therapy will make islet replacement therapy widely accessible to millions of patients in need. Disease Focus of Abstract:Diabetes"

Diabetes • Metabolic Disorders • Solid Organ Transplantation • Type 1 Diabetes Mellitus

An Efficacy, Safety, and Tolerability Study of VX-880 in Participants With Type 1 Diabetes With a Kidney Transplant (clinicaltrials.gov) - P3 | N=10 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Phase classification: P2 ➔ P3 | Trial completion date: Sep 2030 ➔ Sep 2027

Phase classification • Trial completion date • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

IMPROVEMENT IN GLYCEMIC CONTROL AND ELIMINATION OF EXOGENOUS INSULIN USE IN PATIENTS WITH TYPE 1 DIABETES INFUSED WITH FULLY DIFFERENTIATED ISLET CELLS: TRIAL VX-880-101 (FORWARD) (ATTD 2025) - "VX-880 safety was consistent with immunosuppressive regimen, islet infusion procedure, and long-standing T1D. Conclusions VX-880 has curative potential in T1D with elimination of severe hypoglycemia, significantly improved glycemic control, and freedom from exogenous insulin use."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Infectious Disease • Metabolic Disorders • Otorhinolaryngology • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Vascular Neurology

An Efficacy, Safety, and Tolerability Study of VX-880 in Participants With Type 1 Diabetes With a Kidney Transplant (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

An Efficacy, Safety, and Tolerability Study of VX-880 in Participants With Type 1 Diabetes With a Kidney Transplant (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P2 trial • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes (clinicaltrials.gov) - P3 | N=52 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Phase classification: P1/2 ➔ P3 | N=37 ➔ 52 | Trial completion date: Feb 2030 ➔ Jun 2030 | Trial primary completion date: Feb 2026 ➔ Jun 2027

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Improvement in glycaemic control and elimination of exogenous insulin use in patients with type 1 diabetes infused with fully differentiated islet cells (VX-880) (EASD 2024) - P1/2 | "These results demonstrate that a single infusion of VX-880, an allogeneic stem cell-derived, fully differentiated islet cell therapy, has the potential to eliminate severe hypoglycemia, significantly improve glycemic control, and achieve freedom from use of exogenous insulin. Data support the curative potential of VX-880 in people with T1D."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=37 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | N=17 ➔ 37 | Trial completion date: Jan 2028 ➔ Feb 2030 | Trial primary completion date: Jan 2024 ➔ Feb 2026

Enrollment change • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Targeting mRNA Modifications to counter type 1 diabetes (ATTD 2024) - "5) Vertex Announces Positive Day 90 Data for the First Patient in the Phase 1/2 Clinical Trial Dosed With VX-880, a Novel Investigational Stem Cell-Derived Therapy for the Treatment of Type 1 Diabetes...7) Reardon, S. First pig-to-human heart transplant: what can scientists learn? Nature 601, 305–306 (2022)."

Diabetes • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

Glucose-Dependent Insulin Production and Insulin-Independence in Type 1 Diabetes from Stem Cell-Derived, Fully Differentiated Islet Cells: Updated Data from the VX-880 Clinical Study (IPITA-IXA-CTRMS 2023) - " These results demonstrate that a single infusion of stem cell-derived islets (VX-880) can restore insulin production and glucose regulation, leading to insulin independence in patients with T1D. Based on this, VX-880 has the potential to be a functional cure for patients with T1D. Part B is fully enrolled and multiple additional patients have been dosed with the target dose."

Clinical • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Glucose-dependent insulin production and insulin-independence in patients with type 1 diabetes infused with stem cell-derived, fully differentiated islet cells (VX-880) (EASD 2023) - P1/2 | "These results demonstrate that a single infusion of stem cell-derived islets (VX-880) can restore insulin production and glucose regulation, leading to insulin independence in patients with T1D. Based on this, VX-880 has the potential to be a functional cure for patients with T1D. Part B is fully enrolled and multiple additional patients have been dosed with the target dose."

Clinical • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus