Positive results in type 1 diabetes cell therapy study

All six people treated with engrafted islet cells in a clinical trial produced endogenous insulin (C-peptide) and had improved glycaemic control while reducing or eliminating insulin use, according to results presented at the American Diabetes Association’s 83rd Scientific Sessions.

Vertex Pharmaceuticals Incorporated presented data on June 23 on all patients dosed in Parts A and B of its Phase 1/2 clinical trial of VX-880, an investigational stem cell-derived, fully differentiated islet cell therapy, in people with type 1 diabetes with impaired hypoglycaemic awareness and severe hypoglycaemic events (SHEs).

Study participants treated with VX-880 had undetectable fasting C-peptide (endogenous insulin secretion) at baseline, a history of recurrent SHEs in the year prior to treatment and required an average of 34.0 units of insulin per day, according to the study.

Following treatment, all six participants demonstrated endogenous insulin secretion, improved glycemic control as measured by HbA1c, improved time-in-range on continuous glucose monitoring, and reduction or elimination of exogenous insulin use. Patients with greater than 90 days of follow-up had elimination of SHEs in the evaluation period.

One patient in Part A received a half-target dose of VX-880 and was followed for approximately nine months, at which time this patient received a second half dose, scientists reported. This patient subsequently withdrew consent (not related to adverse events [AEs]) and was therefore not evaluable for the primary endpoint, according to the study.

These data represent a foundational advance in the potential treatment of T1D, bringing us one step closer to a potentially curative therapy for patients who are waiting. Dr Felicia Pagliuca, Disease Area Executive, Type 1 Diabetes at Vertex.
Two patients treated with VX-880 had at least 12 months of follow-up after the last infusion and were therefore evaluable for the study’s primary efficacy endpoint of elimination of SHEs between Day 90 and Month 12 with a reduction of HbA1c (<7.0% or a decrease of at least 1% compared to baseline). Both of these patients met the criteria for the primary endpoint of the study, Vertex said. In addition, these two patients are insulin independent. Patient A1 had HbA1c of 5.3% at Month 21, compared to 8.6% at baseline, and Patient B1 had HbA1c of 6.0% at Month 12, compared to 7.6% at baseline. Both patients showed over 95% time-in-range based on continuous glucose monitoring. The ADA recommended target is ≥70%.

The three additional patients in Part B, each administered the full target dose of VX-880 given as a single infusion, have follow-up between 29 and 90 days and have shown endogenous insulin secretion, reduction in HbA1c, improvements in glucose time-in-range, and reductions in daily exogenous insulin use. Their trajectory is consistent with that observed in the two patients with more than one year of follow-up at equivalent periods of follow-up after VX-880 infusion.

VX-880 has been generally well tolerated in all patients dosed to date. The majority of AEs were mild or moderate, and there were no serious AEs related to VX-880 treatment. The most common AEs were dehydration, diarrhea, hypomagnesemia and rash. As previously reported, one subject had SHEs in the perioperative period.

As a result of these safety and efficacy data in Parts A and B, the independent data review committee has recommended moving to Part C of the trial, which allows for concurrent dosing of patients at the full target dose of VX-880.

Dr Felicia Pagliuca, Disease Area Executive, Type 1 Diabetes at Vertex, said: “These data represent a foundational advance in the potential treatment of type 1 diabetes, bringing us one step closer to a potentially curative therapy for patients who are waiting. These data are particularly meaningful in the context of our overall investigational T1D program, as these same VX-880 cells are the building blocks for our Phase 1/2 VX-264 cells-plus-device program, as well as our research-stage hypoimmune islet cell program.”

Dr Trevor Reichman, from the Department of Surgery, University of Toronto, said: “The reproducible efficacy across multiple patients and endpoints, including the level of glucose control and the elimination of SHEs, observed in this trial is highly unusual in T1D patients treated with exogenous insulin, wherein only ~25% of people with T1D meet the recommended HbA1c target of 7.0%, and is truly remarkable. The normalization of HbA1c without the need for exogenous insulin one year after therapy with VX-880 is historic and offers hope that the transformative therapies the T1D community has been waiting for may finally become reality.”

These data were presented during the American Diabetes Association 83rd Scientific Sessions Conference on June 23, 2023 in San Diego, California at 3.50pm PT as an oral presentation, ‘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 Trial’, as part of the ‘Designer Beta Cells’ symposium from 3.45pm to 5.15 pm PT.