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SAN DIEGO -- Stem cell-derived islet cell therapy continued to show promise for the management of type 1 diabetes (T1D) with severe hypoglycemia, according to results from a small phase I/II clinical trial.

All six Part A and B study participants showed endogenous insulin secretion, improved glycemic control, improved time-in-range on continuous glucose monitoring, and reduced need for exogenous insulin after a single infusion of the investigational islet cell therapy (VX-880), reported Trevor Reichman, MD, PhD, of the University of Toronto, who presented the results here at the American Diabetes Association (ADA) Scientific Sessions.

Moreover, two of the three initial recipients of the cell therapy at half the target dose, the Part A arm, showed an elimination of severe hypoglycemic events (SHEs) over more than 1 year of follow-up (the third individual in Part A had withdrawn consent, for reasons not related to side effects, after getting two half-doses 9 months apart).

Three additional Part B patients receiving the target dose of VX-880 have a trajectory that appears consistent with the prior cohort, according to Reichman.

He reported that two patients were also deemed as having achieved insulin independence, defined as having at least one week off exogenous insulin, an HbA1C ≤7%, post-prandial serum glucose ≤180 mg/dL at 90 minutes, fasting serum glucose ≤126 mg/dL, and fasting or stimulated C-peptide ≥166 pmol/L, while also exceeding the ADA's target-time in range:

• One Part A patient who received half-dose VX-880 achieved insulin independence at 9 months and sustained it through 21 months
• One Part B patient who received target-dose VX-880 achieved insulin independence at 6 months and sustained it through 12 months

This is one more patient with full insulin independence than the study's initial Part A report from last year. Based on the overall results, the treatment is advancing to Part C of the trial, which allows for concurrent dosing at the full target dose.

"I think the most unexpected thing was that [the islet cell transplants] worked as well as they did, and that the patients that were far out enough actually became insulin independent," Reichman told 番茄社区app.

"[The study] met all of the efficacy endpoints of eliminating SHEs, which was the primary endpoint [and] reason the patients were enrolled -- they had really debilitating diabetes," he said. "Obviously it improved the management of their diabetes."

VX-880 is an investigational allogeneic stem cell-derived, fully differentiated islet cell therapy, where patients are placed on an immunosuppression regimen to receive engrafted islet cells via an infusion through the hepatic portal vein. Should the treatment prove successful, the therapy and its associated immunosuppression would be a lifelong therapy for the patient, according to Reichman, "similarly to any transplant recipient."

The FDA had previously placed a clinical hold on the VX-880 trial in May 2022, just before the trial's presentation at ADA's previous meeting, citing a lack of information regarding the study's dose-escalation procedures. The hold was lifted a few months later.

In order to be eligible for the study, patients needed to be ages 18 to 65 years, be diagnosed with T1D, needed to exhibit impairment of their hypoglycemic awareness, and had to have experienced at least two SHEs in the previous year.

Reichman told 番茄社区app that in the future, he hopes the inclusion criteria for engrafted islet cell research can be expanded to help a wider pool of T1D patients.

The six trial participants in the present report had an average age of 44. Male and female patients were evenly represented. On average, patients had diabetes for 23 years, an HbA1C of 8.13%, and a body mass index of 23.5.

The majority of adverse events reported during the duration of the trial were considered to be mild to moderate in nature. Mild or moderate events that were linked to treatment were likely in relation to immunosuppressive therapy. Serious adverse events included rash, dehydration, confusional state, migraine, neutropenia, and small intestinal obstruction -- all ultimately not attributed to VX-880.

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