Phase 3 Trial of Vertex’s Islet Cell Therapy for Type 1 Diabetes Under Way

Vertex Pharmaceuticals is conducting the pivotal phase 3 portion of a phase 1/2/3 study of zimislecel (formerly VX-880) in those with type 1 diabetes who have had severe hypoglycemic events. Hypoglycemia is a potentially life-threatening low-blood-sugar condition.

Zimislecel is an investigational allogeneic, or donor, stem cell-derived islet cell therapy that is delivered by an infusion into the liver portal vein. The therapy aims to replace the insulin-producing cells that have been destroyed in people with type 1 diabetes. It is expected that patients will require anti-rejection medication to prevent the islet cells from being rejected.

Vertex expects to complete enrollment and dosing of about 50 patients in 2025, with regulatory submissions to the FDA, the European Medicines Agency and the UK Medicines and Healthcare Products Agency expected in 2026.

The single-arm, open-label trial of zimislecel is enrolling adults 18 years of age to 65 years of age in 25 locations worldwide who have not previously had an islet cell transplant, an organ transplant or cell therapy. The trial will assess patients at one year after insulin independence for the proportion of those who are still insulin independent and who have not had hypoglycemic events. The safety and tolerability for up to five years will be monitored.

Type 1 diabetes is an autoimmune disease where the immune system destroys insulin-producing beta cells in pancreatic islets. Insulin deficiency results in hyperglycemia and can lead to acute life-threatening complications such as diabetic ketoacidosis. Patients rely on insulin and careful monitoring of blood glucose levels.

About 2 million Americans have type 1 diabetes. Vertex officials estimate that about 125,000 patients have severe type 1 diabetes, and if approved for this indication, zimislecel could be appropriate for approximately 60,000 people with severe type 1 diabetes.

Last year, Vertex released results from 12 patients in the phase 1/2 part of the trial of zimislecel. All 12 patients who received the full dose as a single infusion demonstrated islet cell engraftment and glucose-responsive insulin production by day 90. Of the 12 patients, one was able to eliminate insulin injections.

All patients had improved glycemic control and achieved ADA-recommended targets for both HbA1c below 7.0% and time-in-range above 70% on continuous glucose monitoring. Additionally, all 12 patients were free of severe hypoglycemic events during the evaluation period.

The majority of adverse events (AEs) were mild or moderate, and there were no serious adverse events related to treatment.

Breakthrough T1D and the T1D Fund provided grants and funding to ViaCyte and Semma Therapeutics to facilitate early development of the sBC line. By 2022, Vertex had acquired both companies and has fully funded research of zimislecel since then.

Vertex is also pursuing alternative approaches to immunosuppression that could be used with zimislecel, as well as a hypoimmune program using gene-edited stem-cell-derived islets.

Related: New Type of Stem Cell Transplant Shows Promise in Type 1 Diabetes

In June 2023, the FDA approved CellTrans’ Lantidra (donislecel) as the first cellular therapy for type 1 diabetes. But Lantidra es not use stem cell-based allogeneic cells. The cells are unmodified cadaver-sourced cells, and cannot be replicated or produced at scale. This is one of the primary limitations of Lantidra, as the limited cell supply restricts the therapy to only those with severe, uncontrolled diabetes.