Novel islet cell therapy eliminates severe hypoglycemia, cuts HbA1c in type 1 diabetes
Key takeaways:
- Adults with type 1 diabetes and recurrent severe hypoglycemia reduced their HbA1c to less than 7% with a full dose of VX-880.
- No severe adverse events associated with the therapy were reported.
A novel islet cell therapy delivered through a single infusion lowered HbA1c and eliminated severe hypoglycemia events for all adults with type 1 diabetes who received a full dose, according to data from a phase 1/2 study.
As Healio previously reported, the FDA cleared an investigational new drug application for VX-880 (Vertex Pharmaceuticals) to treat adults with type 1 diabetes who experience recurrent severe hypoglycemia. Vertex presented data from the first two participants who received a half dose of VX-880 at the American Diabetes Association Scientific Sessions in 2022.
At the International Conference on Advanced Technologies & Treatments for Diabetes, Michael R. Rickels, MD, MS, the Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases in the division of endocrinology, diabetes and metabolism, and medical director of the pancreatic islet cell transplant program at University of Pennsylvania Perelman School of Medicine, presented additional data from 14 adult participants in the phase 1/2 FORWARD trial.
“The full dose of VX-880, given as a single infusion, demonstrates consistent engraftment of islets with restoration of endogenous insulin secretion, elimination of severe hypoglycemia and significant improvement of glycemic control,” Rickels said during a presentation.
VX-880 is a fully differentiated insulin-producing immunosuppressive islet cell therapy delivered through one infusion. In the open-label phase 1/2 FORWARD study, 14 adults aged 18 to 65 years with type 1 diabetes who had impaired hypoglycemia awareness and experienced at least two severe hypoglycemic events in the year before screening were enrolled (mean age, 43.6 years; nine men). Of the participants, two received a half dose of VX-880, and the remaining 12 received a full dose. The primary endpoint of the trial was the percentage of adults with no severe hypoglycemia events from 90 days until 1 year, plus an HbA1c of less than 7% or a 1 percentage point or greater decrease in HbA1c from 180 days to 1 year.
At 90 days, all participants had clinically meaningful endogenous insulin production and reductions in glucose as revealed during mixed-meal tolerance tests.
From 90 days to 1 year, all 12 participants who received a full dose of VX-880 achieved an HbA1c of less than 7% and had no severe hypoglycemic events. Of the 12 adults receiving the full dose, 11 were able to reduce their dose of exogenous insulin or stop using it entirely at their most recent follow-up visit.
Among adults receiving the full dose, baseline time in range with glucose of 70 mg/dL to 180 mg/dL was 49.5%. Time in range improved to 76.1% at 90 days and 88.3% at 180 days. Among four adults with full follow-up data available, time in range increased further to 94.7% at 270 days and 95.1% at 1 year.
All four adults who had 1 year of follow-up data available met the trial’s primary endpoint and also met a secondary endpoint of achieving insulin independence from 180 days to 1 year.
All 14 study participants experienced an adverse event related to immunosuppressive therapy in the study. Six participants experienced an adverse event related to VX-880. None of the severe adverse events reported in the trial were deemed to be related to VX-880.
“The safety profile is consistent with what is understood about immunosuppressive therapy, the islet infusion procedure and complications of longstanding type 1 diabetes,” Rickels said.
Researchers are now proceeding to a phase 3 trial with a planned enrollment of about 50 adults, with insulin independence serving as the primary endpoint, he said.
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Rickels MR, et al. 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). Presented at: International Conference on Advanced Technologies & Treatments for Diabetes; March 19-22, 2025; Amsterdam (hybrid meeting).
