VX-880 Shows Promise for Insulin, Glucose Management in T1D in New Data

Positive findings from the ongoing VX-880 clinical trial were presented today at the American Diabetes Association (ADA) 83rd Scientific Sessions, raising hope for a stem cell-derived islet cell therapy as a potential future treatment option for individuals with type 1 diabetes (T1D).

The ongoing single-arm, open-label, phase 1/2 trial is being conducted across multiple centers and is primarily focused on adult patients with T1D who have had impaired awareness of hypoglycemia and experienced severe hypoglycemic episodes.

Hypoglycemia, characterized by low blood glucose levels, is common among individuals with T1D and can occur due to various factors such as diet, sleep, stress, and activity levels. In an ADA news release, the authors expressed that current standards of care for T1D do not address the underlying causes of the disease, and treatment options beyond exogenous insulin are limited.

“Over time, people with T1D may lose awareness of hypoglycemia, meaning they may not feel symptoms despite blood glucose readings falling below a level which normally may provoke symptoms, usually below 70 mg/dL,” the press release said. “If left untreated, this can lead to severe hypoglycemic events which can present with loss of consciousness, coma, seizures or serious injury as such, these events can potentially be fatal.”

According to the news release, all 6 patients who received VX-880 in the trial had undetectable insulin secretion and a history of recurrent severe hypoglycemic events (SHE) in the year before receiving the stem cell-derived islet cell therapy.

Following treatment, all 6 patients had restored insulin secretion, improved glycemic control and time in range, reduced or eliminated dependence on external insulin, and completely eliminated SHEs during the evaluation period after day 90 of the trial.

Two patients—one in Part A of the study who received half the target dose, and the other in Part B who received the full target dose—were followed up for at least 12 months and evaluated for the primary efficacy endpoint of eliminating SHEs between day 90 and month 12 while maintaining a hemoglobin A1c (HbA1c) level below 7%.

According to the news release, both patients completed the 12-month follow-up and achieved insulin independence. Compared with an HbA1c of 8.6% at baseline, the patient from Part A significantly improved this level down to 5.3% at month 21. Meanwhile, the patient from Part B achieved an HbA1c level of 6.0% at Month 12, compared with a baseline level of 7.6%.

“This level of glucose control is highly unusual in T1D patients treated with exogenous insulin, with recent data indicating that only approximately 25% of people with T1D meet the recommended HbA1c target of 7.0%,” the news release said.

Remarkably, both patients achieved HbA1c levels below the diagnostic threshold for diabetes (6.5%), and both spent over 95% of their time within the recommended blood glucose range, surpassing the ADA’s target of 70% time-in-range and showcasing significant improvements compared with their baseline measurements.

Three other patients in Part B were administered the full target dose of VX-880 as a single infusion. At day 90 of follow-up, they also exhibited improved insulin production, reduced HbA1c levels, increased time spent within the target blood glucose range, and decreased daily insulin usage.

“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,” the release said.

To date, VX-880 has exhibited a satisfactory safety record and has been well tolerated by all patients who have received it, and the safety profile aligns with that of immunosuppressant therapy and transplantation of islet cells from donors who are deceased. Most reported adverse events were mild or moderate, and there were no serious adverse events associated with VX-880 use.

Because of these positive findings in parts A and B, an independent data review committee has recommended advancing to Part C. This phase will involve administering VX-880 at the full target dosage to patients simultaneously.

“These new findings demonstrate the potential of stem cell-derived islets as a future treatment for patients with type 1 diabetes, signaling a new era that could potentially remove the need for exogenously administered insulin to achieve glycemic control,” said Trevor W. Reichman, MD, PhD, surgical director of pancreas and islet cell transplantation at Ajmera Transplant Center, University of Toronto. “We are hopeful that this first-of-its-kind research could be a gamechanger for the treatment of type 1 diabetes.”

According to ClinicalTrials.gov, the VX-880 trial is still recruiting as of June 18, 2023, and the ADA press release noted the trial has expanded to more sites in Norway, Switzerland, and the Netherlands. The trial has an estimated primary completion date of January 2024 and an estimated study completion date of January 2028.

Reference

Novel stem cell-derived islet cell therapy continues to show promise for achieving insulin independence for individuals with type 1 diabetes. News release. American Diabetes Association. June 23, 2023. Accessed June 23, 2023.