The FDA has lifted a clinical hold on the trial of VX880 placed in May 2022 due to insufficient information.
The FDA has lifted the clinical hold on Vertex Pharmaceuticals’ phase 1/2 clinical trial (NCT04786262) of VX880, a pancreatic islet cell replacement therapy for the treatment of type 1 diabetes with impaired hypoglycemic awareness and severe hypoglycemia.1
The trial, which has been ongoing in Canada, will soon be reopened at multiple sites in the US for screening, enrollment, and dosing. Three patients have been dosed so far, 2 with half the target dose and 1 with the full target dose.
The FDA previously placed the study on hold in May 2022 after the FDA determined there was insufficient information to support dose escalation, despite an Independent Data Monitoring Committee’s recommendation to advance patients to part B of the study and full dosing.2 VX-880 has been well-tolerated with no treatment-related serious adverse events (AEs) reported to date.
“We are surprised by the clinical hold placed on the study. The results from the first 2 patients treated with half the target dose establish proof-of-concept by demonstrating that VX-880 can restore glucose-regulated insulin production and improve glycemic control. Indeed, achievement of insulin independence by the first patient is a landmark milestone,” Carmen Bozic, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex, said in the statement.2
While the trial remained on hold, Vertex presented positive data on the first 2 patients dosed at the American Diabetes Association (ADA) 82nd Scientific Sessions Conference on June 6, 2022, in New Orleans, Louisiana.3 Data were presented by James F. Markmann, MD, PhD, chief, division of transplantation, and surgical director, liver, pancreas and islet transplant programs, and clinical director, MGH transplant center.
Investigators found that VX880 reduced insulin dependence in the first 2 patients. Patients also experienced glucose-responsive insulin production, improvements in glycemic control and reductions in exogenous insulin requirements. There were significant increases from baseline in the blood glucose time-in-range between 70 and 180 mg/dL. The accepted ADA/European Association for the Study of Diabetes (EASD) target for time-in-range is 70%.
Blood glucose time-in-range increased from 40.1% at baseline to 99.9% at Day 270 in patient 1, who became insulin independent. Time-in-range increased from 35.9% at baseline to 51.9% at Day 150 in patient 2, who had a 30% reduction in exogenous insulin use. Data is not yet available for patient 3, who has been treated with the full dose. The therapy continued to be well-tolerated.
“The glucose time-in-range data presented today at ADA demonstrate the remarkable glycemic control that can be achieved after treatment with VX-880,” Bastiano Sanna, PhD, executive vice president and chief, cell and genetic therapies, Vertex, said in a statement.4 “Elevations in blood sugar are important to control, as are fluctuations over time, as both increase the risk of complications in patients with T1D. The first two patients treated with VX-880 have not only achieved improved HbA1c and decreased insulin requirements, but also higher time-in-range. Taken altogether, these data provide further evidence of the potential for VX-880 as a functional cure for people living with T1D.”