SAN DIEGO — An investigational allogeneic stem cell–derived pancreatic islet cell replacement therapy (VX-880, Vertex Pharmaceuticals) continues to show promise as a treatment for type 1 diabetes, according to the latest data, from six patients thus far.
Two of the six are insulin-independent beyond 1 year after receiving the VX-880 infusions, and three others who received them more recently are on a similar trajectory. One dropped out because of reasons unrelated to the therapy. The remaining five are continuing to receive immunosuppressive treatment to prevent rejection of the islets. The six all had undetectable insulin secretion and impaired hypoglycemic awareness and severe hypoglycemia as the criterion to enter the phase 1/2 study.
"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 lead investigator Trevor W. Reichman, MD, PhD, surgical director of Pancreas and Islet Cell Transplantation at the University of Toronto, Canada.
Reichman presented the data at the annual Scientific Sessions of the American Diabetes Association (ADA) last week, as an update to the report of the first two patients at last year's ADA meeting "We are hopeful that this first-of-its-kind research could be a game-changer for the treatment of type 1 diabetes," he emphasized.
Co-investigator Maria Cristina Nostro, PhD, senior scientist at McEwen Stem Cell Institute, Toronto, told Medscape Medical News, "The clinical trial data are extremely exciting…I think what was very beautiful is the glucose tolerance test where the insulin secretion was almost like a person without type 1 diabetes. For someone who is in the lab doing basic science research…all the work we've put into this, it's a labor of love. We've been trying to generate the cells for so long, and now to see this, it's fantastic."
Two Meet Primary Endpoint, Three More on the Right Path
The six patients had a mean age of 44 years, and mean 23 years' diabetes duration. Three each were male and female. Their mean baseline A1c was 8.1%, and fasting C-peptide was undetectable. They had experienced a mean of 3.3 severe hypoglycemia episodes in the year prior to receiving the infusion, which was delivered to the portal vein similarly to the procedure with cadaveric donor islets, Reichman said.
The first two patients, including the one who dropped out, received half target doses of VX-880 (trial part A), while the rest, enrolled sequentially (part B), were each administered the full target dose of VX-880 given as a single infusion.
Induction with anti-thymocyte globulin and maintenance immunosuppressants, tacrolimus/sirolimus, was used to protect the cells from the recipient's immune system. After the infusion, all six participants had C-peptide production, reduction in A1c despite reduced insulin use, and no severe hypoglycemia episodes from day 90 onwards.
Both participants with at least a year of follow-up met the criteria for the primary endpoint of A1c less than 7% with no severe hypoglycemic episodes. The first participant had an A1c of 5.3% at month 21, and the second 6.0% at 12 months. Both had sustained glucose-responsive insulin production with a mixed-meal tolerance test and exceeded the ADA target of more than 70% time-in blood glucose range assessed with continuous glucose monitoring.
Safety: No Major Concerns Thus Far
Among all six, adverse events included elevations in the liver enzyme transaminase, occurring shortly after VX-880 infusion that were transient and resolved. No serious adverse events were considered related to the therapy.
Regarding safety, Nostro said, "With this trial, I have no concerns because they're using immunosuppression, so should anything go bad you remove immunosuppression and the cells would be destroyed by the immune system. So it's a perfect trial in a way."
However, she noted, "Moving forward, as we develop something that will be genetically modified…I think this is the future because if you're going to treat people with type 1 diabetes we have to eliminate the immune suppression. I think the concern would be making sure the genetically modified cells are safe."
Nostro, who gave an introductory presentation at the beginning of the symposium where the VX-880 data were presented, explained that in a current trial of genetically modified cells, "they're placing the product inside a device so that the cells would be retrievable. It might not be perfect but at least it's going to tell us whether the genetically modified product is safe, which I think is what we need to use."
In her talk, Nostro also summarized ongoing work in this field involving efforts to improve the generation of stem cell–derived islets with no "off target" non-beta cells to ensure consistency, optimization of engraftment, and elimination of immunosuppression.
She told Medscape: "[VX-880] is the beginning. This is the first product that's going to be in the clinic, but I can imagine how five, 10 years from now we will have different and more enhanced solutions for type 1 diabetes and who knows, maybe even for type 2."
Based on the data so far, the VX-880 trial is now moving to part C, in which 10 concurrently enrolled participants will receive the full target dose of the product. The trial, previously exclusively in the United States, has now expanded to additional sites in Norway, Switzerland, and the Netherlands.
The study was funded by Vertex. Reichman is on advisory boards for Vertex and Sernova Inc. Nostro was a consultant for Sigilon Therapeutics from 2018-2022, currently receives research support from Universal Cells, and has a patent licensed to Sernova.
Annual Scientific Sessions of the American Diabetes Association.
Abstract 836-P. Presented June 23, 2023.
Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.
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Cite this: 33% of Type 1 Diabetes Patients Insulin-Free With Stem Cells - Medscape - Jul 03, 2023.