FDA Lifts Clinical Hold on Vertex’s Experimental Cell Therapy for Type 1 Diabetes

Rare Daily Staff

The U.S. Food and Drug Administration has lifted the clinical hold placed on the phase 1/2 clinical trial of Vertex Pharmaceutical’s VX-880, an experimental stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with type 1 diabetes with impaired hypoglycemic awareness and severe hypoglycemia.

In May 2022, the agency placed a hold on the trial because it felt there wasn’t sufficient information to support dose escalation. The company said it now expects the phase 1/2 trial will be reopened for screening, enrollment, and dosing at multiple sites in the United States.

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing islet cells in the pancreas, leading to loss of insulin production and impairment of blood glucose control. The absence of insulin leads to abnormalities in how the body processes nutrients, leading to high blood glucose levels. High blood glucose can lead to diabetic ketoacidosis and over time, to complications such as kidney disease/failure, eye disease (including vision loss), heart disease, stroke, nerve damage and even death.

Due to the limitations and complexities of insulin delivery systems, it can be difficult to achieve and maintain balance in glucose control in people with T1D. Hypoglycemia often results because of the difficulty in balancing the different factors that impact glucose levels, including insulin, diet and exercise. Hypoglycemia remains a critical limiting factor in glycemic management, and severe hypoglycemia can cause loss of consciousness, coma, seizures, injury and can be fatal. Over time, patients with T1D can develop impaired awareness of hypoglycemia, meaning they are no longer able to perceive the early signs of a hypoglycemic event, which can be dangerous and result in life-threatening events.

Current standards of care do not address the underlying causes of the disease, and there are limited treatment options beyond insulin for the management of T1D.

VX-880 is an experimental allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy manufactured using proprietary technology. VX-880 is being evaluated for patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. VX-880 has the potential to restore the body’s ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose responsive insulin production. VX-880 is delivered by an infusion into the hepatic portal vein and requires maintenance immunosuppressive therapy to protect the islet cells from immune rejection.

The clinical trial is a phase 1/2, multi-center, single-arm, open-label study in patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. This study is designed as a sequential, multi-part clinical trial to evaluate the safety and efficacy of VX-880. In Part A, the first two patients received half the target dose. In Part B, five patients will receive the target dose, after which concurrent dosing at the full target dose will occur in Part C. Approximately 17 patients will be enrolled in the clinical trial. Enrollment is ongoing in this study.

To date, three patients have been dosed in the phase 1/2 study with VX-880. Two patients received half the target dose of cells in Part A of the study. A third patient has received the full target dose in Part B of the study. Part B will evaluate safety and efficacy in five patients at the target dose before expanding to additional patients in Part C.