Stem Cell-Derived Therapy Improves Glucose Control in Type 1 Diabetes

Trevor Reichman, MD

Credit: University of Toronto

People with type 1 diabetes (T1D) treated with stem cell-derived islet cells (VX-880) have exhibited improved blood sugar control, with half achieving insulin independence, according to new results from a phase 1/2 trial.¹

Presented at the 2023 Annual Meeting of the European Association for the Study of Diabetes (EASD), the findings detailed the 6 adults treated with VX-880. All experienced an improvement in glycemic control and a significant reduction in their externally administered insulin needs.

“All patients who have been treated with VX-880 have shown improvements across all measures of glucose control, including reduction or even elimination of external insulin use,” said Trevor Reichman, MD, a professor in the department of surgery at the University of Toronto.

People with T1D do not have functional cells in the pancreas to produce the body’s own insulin – instead, they require daily insulin injections or pumps to survive.

The phase ½ trial evaluated VX-880 in adults with impaired hypoglycemic awareness and a history of severe hypoglycemic events. These patients are unable to perceive the symptomatic presentation of low blood sugar and could experience low blood sugar levels they are unable to recover from without assistance.²

“These results are truly remarkable and offer hope of a life-changing therapy for people who suffer from the relentless life-long burden of type 1 diabetes,” Reichman said.

The trial is ongoing and is in the final part of 3 parts. In Part A of the trial, 2 patients were enrolled sequentially and received half the target dose of VX-880. Patient 2 subsequently withdrew consent and discontinued participation in the trial for personal reasons, rather than an adverse event.

In Part B of the trial, 5 patients were enrolled sequentially and received the target dose. Parts A and B completed enrollment; Part C is underway and will enroll 10 patients concurrently to receive the target dose.

For this analysis, investigators reported on all patients included in Parts A and B who were followed up with for ≥90 days.¹ After a single infusion of VX-880, patients were assessed for safety and tolerability, fasting and stimulated C-peptide levels, measures of blood glucose control, and external insulin use.

In Part A, after a VX-880 infusion at half the target dose, Patient 1 achieved insulin independence after 9 months. Insulin independence was sustained at the most recent visit at 24 months. Investigators noted this patient has more than a 40-year history of living with severe T1D and was using an average of 34 units of insulin per day prior to trial enrollment.

In Part B, after VX-880 infusion at the target dose, Patient 3 achieved insulin independence after 6 months, which was sustained until the 12-month visit. Investigators noted the patient had a 19-year history of living with T1D and needed an average of 45 units of insulin per day prior to trial enrollment. After 15 months, Patient 3 was started on four units of daily insulin. Recently, Patient 4 reached day 180 and achieved insulin independence.

Overall, study participants reported improved glycemic control, reduction in HbA1c, and an increase in the amount of time their blood glucose levels were in the recommended range. In addition, there was a reduction in, or elimination of external insulin needs and elimination of hypoglycemia for ≥90 days.

Regarding safety outcomes, VX-880 was generally safe and well-tolerated in the patient cohort. Most adverse events were mild or moderate, with 2 non-serious adverse events of elevated transaminases and no serious events related to treatment. Post-procedure, at 90 days, all patients in Parts A and B responded to a mixed-meal tolerance test by triggering the production of insulin, suggesting the injected islet cells were working as intended.

However, despite the positive findings, the new cells are at risk from the body’s immune system and require immunosuppressants to help prevent rejection, which can provide its own risk.

“The future goal is to create a version of the treatment that does not require immunosuppressive therapy”, Reichman said. “The makers of VX-880 are working on encapsulating the cells in a device that would allow them to evade the immune system as well as genetically modifying the cells so they won’t initiate an autoimmune attack.”

References

1. New stem cell-derived islet therapy improves blood sugar control in all treated patients, with three achieving insulin independence. EurekAlert! October 3, 2023. Accessed October 4, 2023. https://www.eurekalert.org/news-releases/1003384.
2. Iapoce C. Phase 1/2 data show potential of VX-880 for insulin independence in T1D. HCP Live. June 24, 2023. Accessed October 4, 2023. https://www.hcplive.com/view/data-potential-vx-880-insulin-independence-t1d.