The company reports positive data from first 2 patients dosed, but the agency determined there is insufficient information to support dose escalation.
The US Food and Drug Administration (FDA) has placed a clinical hold on Vertex Pharmaceuticals’ phase 1/2 study (NCT04786262) of VX-880 for the potential treatment of patients with type 1 diabetes (T1D), the company announced in a statement also reporting positive data based on the first 3 patients dosed in the study.1
Two patients in Part A of the study received a half dose of VX-880, an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with T1D with impaired hypoglycemic awareness and severe hypoglycemia. At day 270, the first patient reported insulin independence and an HbA1c of 5.2%, while the second patient has “shown robust increases in fasting and stimulated C-peptide, and reductions in exogenous insulin requirements through Day 150,” according to Vertex, which claimed the results, taken together, establish proof-of-concept for the therapy. A third patient who received a full dose of VX-880 achieved the Day 29 follow-up milestone.
VX-880 has been generally well-tolerated, with no serious adverse events related to the therapy reported to date.
The Independent Data Monitoring Committee has reviewed the safety and efficacy data related to the first 2 Part A patients dosed and recommended the advancement of the patients to Part B, or full dosing. However, the FDA determined there is insufficient information to support dose escalation.
“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.
“Further, the totality of the safety and efficacy data for all 3 patients dosed to date gives us high confidence in our benefit-risk assessment of VX-880 and its potentially transformative profile,” Bozic continued. “We are committed to working with the FDA to understand and address their questions, so that the trial can resume at US sites as soon as possible.”
VX-880 is an investigational, stem cell-derived, fully differentiated pancreatic islet cell replacement therapy. It is designed to restore islet cell function to be able to regulate glucose levels and insulin production. It is infused into the hepatic portal vein and treated patients require chronic immunosuppressive therapy.
The phase 1/2 trial is a multi-center, single-arm, open-label study that is designed to be sequential, with multiple parts. Part A evaluates patients receiving half the target dose. Then, in Part B, 5 patients will receive the full dose. Concurrent dosing at the full target dose will take place in Part C.
The FDA granted fast track designation to VX-880 in March 2021,2 after approving an Investigational New Drug application for it in January 2021.