A single infusion of a stem cell-based treatment may have cured 10 out of 12 people with the most severe form of type 1 diabetes, say scientists. One year later, these 10 patients no longer need insulin, while the other two patients need much lower doses.
The experimental treatment, called zimislecel and made by Vertex Pharmaceuticals of Boston, United States, involves stem cells that scientists prodded to turn into pancreatic islet cells, which regulate blood glucose levels. The new islet cells were infused and reached the liver, where they took up residence.
The study was presented this weekend at the annual meeting of the American Diabetes Association and published online by The New England Journal of Medicine.
“It’s trailblazing work,” said Dr Mark Anderson, Professor and director of the diabetes centre at the University of California in San Francisco, who was not involved in the study. “Being free of insulin is life-changing.”
Vertex, like other drug companies, declined to announce the treatment’s cost before the US Food and Drug Administration approves it, reports The New York Times.
A Vertex spokeswoman said the company had data only on the population it studied so it could not yet say whether the drug would help others with type 1 diabetes.
The patients in the study are among the estimated 30% with a complication of type 1 diabetes – hypoglycaemic unawareness. Those with the condition have no warning when their glucose levels are falling precipitously. They lack the normal signs like shakiness or sweating that can signal a need for glucose.
Patients with hypoglycaemic unawareness can suddenly pass out or have seizures or even die.
“It’s a frightening way of life,” said Dr Trevor Reichman, director of the pancreas and islet transplant programme at University Health Network, a hospital in Toronto, and first author of the study.
Patients in the study began to need less insulin within a few months of being infused with new islet cells, and most stopped needing the hormone altogether at about six months, he said.
He added that patients’ episodes of hypoglycaemia went away within the first 90 days of treatment.
If the study continues to show positive results, the company expects to submit an application to the FDA next year.
“For the short term, this looks promising for severely affected patients like those in the study,” said Dr Irl Hirsch, a diabetes expert at the University of Washington who was not involved in the study.
But patients in the trial had to stay on drugs to prevent the immune system from destroying the new cells. Suppressing the immune system, he said, increases the risk of infections and, over the long term, can increase the risk of cancer.
“The argument is this immunosuppression is not as dangerous as what we typically use for kidneys, hearts and lungs, but we won’t know that definitely for many years,” Hirsch said.
Patients may have to take the immunosuppressant drugs for the rest of their lives, the Vertex spokeswoman said.
The treatment is the culmination of work that began more than 25 years ago when a Harvard researcher, Doug Melton, vowed to find a cure for type 1 diabetes. His six-month-old son developed the disease and then so did his adolescent daughter. His passion was to find a way to help them and other patients.
He began, he said, “with an unwavering belief that science can solve the most difficult problems”.
It took 20 years of painstaking, repetitive, frustrating work by Melton and a team of about 15 people to find the right chemical cocktail to turn stem cells into islet cells. He estimated that Harvard and others spent $50m on the research.
Dr Peter Butler, a Professor of medicine at the University of California, Los Angeles, and a consultant to Vertex, said he was awed by the achievement of the Harvard team.
“The fact that it worked at all is just amazing to me,” he said. “I can guarantee there were a thousand negative experiments for every positive one.”
When Melton finally succeeded, he needed a company to take the discovery into the clinic. He joined Vertex, which took up the challenge.
The first patient to get the experimental therapy, Brian Shelton, got an infusion in 2021. He had been plagued by episodes of plummeting blood sugar that made him lose consciousness. Once he crashed his motorcycle into a wall, and another time he passed out in a yard while working his mail delivery route.
The infusion cured him, but he died shortly afterward from what Vertex described as dementia symptoms that began before his treatment.
Recruitment of the 12 patients in the new report proceeded slowly, Reichman said, because of the strict entry requirements. Some who qualified backed out when they heard they would have to take immunosuppressive drugs, he added.
One who joined, a 36-year-old nurse in Ontario, said she jumped at the chance to enter the trial. Six months after the infusion, she no longer needed insulin.
“It’s like a whole new life,” she said.
Study details
Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes
Trevor Reichman, James Markmann, Jon Odorico et al.
Published in New England Journal of Medicine on 20 June 2025
Abstract
Background
Zimislecel is an allogeneic stem cell–derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed.
Methods
We conducted a phase 1–2 study of zimislecel in persons with type 1 diabetes. In part A, participants received a half dose of zimislecel (0.4×109 cells) as a single infusion into the portal vein, with an option for a second half dose within 2 years. In parts B and C, participants received a full dose of zimislecel (0.8×109 cells) as a single infusion. All the participants also received glucocorticoid-free immunosuppressive therapy. The primary end point in part A was safety. The primary end point in part C was freedom from severe hypoglycaemic events during days 90 through 365, with a glycated hemoglobin level of less than 7% or a decrease of at least 1 percentage point from baseline in the glycated haemoglobin level at one or more time points between days 180 and 365. Secondary end points in part C included safety and insulin independence between days 180 and 365. Assessment of the primary and secondary end points in part C involved the participants who received the full dose of zimislecel as a single infusion in part B or C. Detection of serum C-peptide during a 4-hour mixed-meal tolerance test was used to assess engraftment and islet function. All the analyses were interim and not pre-specified.
Results
A total of 14 participants (2 in part A and 12 in parts B and C) completed at least 12 months of follow-up and were included in the analyses. C-peptide was undetectable at baseline in all 14 participants. After zimislecel infusion, all the participants had engraftment and islet function, as evidenced by the detection of C-peptide. Neutropenia was the most common serious adverse event, occurring in 3 participants. Two deaths occurred — one caused by cryptococcal meningitis and one by severe dementia with agitation owing to the progression of pre-existing neurocognitive impairment. All 12 participants in parts B and C were free of severe hypoglycaemic events and had a glycated haemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per decilitre). Ten of the 12 participants (83%) had insulin independence and were not using exogenous insulin at day 365.
Conclusions
The results of this small, short-term study involving persons with type 1 diabetes support the hypothesis that zimislecel can restore physiologic islet function, warranting further clinical investigation.
NEJM article – Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes (Open access)
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