Frank Vinluan , 2025-06-23 18:44:00
A Vertex Pharmaceuticals cell therapy for type 1 diabetes is enabling patients to produce insulin, eliminating the need for additional insulin therapy in the vast majority of participants in a key clinical trial. With these preliminary results in hand, the drugmaker is eyeing 2026 regulatory submissions of the therapy, zimislecel.
The update comes from the Phase 1/2 portion of an open-label Phase 1/2/3 study and covers 12 patients who had been followed for at least one year. Vertex said all 12 achieved levels of blood glucose in the range recommended by the American Diabetes Association (ADA). Type 1 diabetes treatment requires blood glucose monitoring and frequent or continuous dosing of insulin. Vertex said 10 of the 12 patients treated with zimislecel were free as this exogenous insulin as of the data cutoff date. The latest results were presented late Friday during the ADA’s annual conference in Chicago and published online in the New England Journal of Medicine (NEJM).
Type 1 diabetes is an autoimmune disorder that leads to destruction of pancreatic islet cells that produce insulin. Of the 3.8 million diagnosed type 1 diabetes patients in the U.S. and Europe, about 60,000 experience life-threatening severe hypoglycemic events (SHEs), Vertex said in an investor presentation. This is the patient population Vertex is targeting for zimislecel.
Zimislecel (formerly known as VX-880) consists of stem cell-derived islet cells that are administered as a single infusion into the hepatic portal vein. In order to prevent the body from rejecting the cell therapy, zimislecel requires chronic use of immunosuppressive drugs. These drugs introduce complication risks, such as a higher susceptibility to infections.
Vertex had hoped to avoid chronic immunosuppression with a different program, VX-264. This therapeutic candidate encapsulated zimislecel in an implanted medical device that protected the cell therapy from the immune system. In March, Vertex discontinued VX-264 after it fell short of efficacy goals in a Phase 1/2 clinical trial. But the company continued development of “naked” zimislecel — the cell therapy without the protective medical device.
While avoiding immunosuppression would have given Vertex a key advantage in type 1 diabetes treatment, naked zimislecel still has potential for differentiation. The only FDA-approved cell therapy for this disease is Lantidra, which biotech company CellTrans makes from islet cells that come from deceased donors. Limitations of Lantidra include ensuring the quality and supply of cells sourced this way. Stem cell-derived zimislecel offers patients the prospect of an “off the shelf” treatment alternative.
The latest results for zimislecel show the stem cell-derived islet cells were accepted by patients’ bodies and led to production of C-peptide. This peptide is released alongside insulin and measuring its levels in the blood offers a way to assess insulin production. Vertex said the therapy continues to be well tolerated, with most adverse effects classified as mild or moderate. The NEJM article states the most common serious adverse event was neutropenia, which is low levels of type of white blood cell called a neutrophil. This event was reported in three patients. Vertex said no serious adverse effects related to the cell therapy were reported and the safety profile is consistent with the immunosuppressive regimen used in the study. Two previously reported patient deaths were unrelated to treatment with zimislecel, the company said.
In a note sent to investors Monday, William Blair analyst Myles Minter said zimislecel’s ability to help maintain normal blood glucose levels while reducing or eliminating the need for exogenous insulin represents a meaningful lifestyle difference for patients. He also noted that experts say 35% to 40% of type 1 diabetes patients cannot achieve ADA glucose control guidelines with currently available treatments, which makes the target addressable market for zimislecel significantly larger than the 60,000 patients targeted by Vertex. But the cell therapy still faces hurdles.
“We view the requirement for immunosuppressants as the largest headwind here for commercial uptake, which may preclude certain patient populations, and serious adverse events involving neutropenia and acute kidney injury were noted in the NEJM publication,” Minter said.
In the investor presentation, Vertex said it is developing immunosuppression alternatives that are currently in the research stage. Meanwhile, the Phase 1/2/3 test of zimislecel is expected to enroll a total of 50 patients. Vertex expects to complete enrollment and dosing this summer.
Photo: David L. Ryan/The Boston Globe, via Getty Images
