Type 1 Diabetes: Early Results Of Cell Therapy Point To Revolution In Treatment

A new experimental treatment for type 1 diabetes, called zimislecel, uses insulin-producing stem cells to try to replace cells destroyed by the immune system. In a small study, most participants were able to stop taking insulin and keep their blood sugar under control, without severe hypoglycemia. Despite the promising results, the treatment still carries risks, such as infections, and needs more testing before it is available.

Type 1 diabetes (T1D) is an autoimmune disease, meaning a person’s own immune system attacks and destroys the cells in the pancreas that produce insulin. Insulin is essential because it allows sugar (glucose) in the blood to enter the body’s cells and be used for energy.

When these cells are destroyed, sugar builds up in the blood, which can cause serious health problems if left unchecked. That’s why people with type 1 diabetes need to take insulin every day and carefully control their diet and blood sugar levels.

Even so, it's difficult to avoid dangerous swings in blood sugar, which can lead to situations like severe hypoglycemia (when blood sugar drops too low and a person may faint or have seizures).

The study in question tested a new, experimental treatment called zimislecel, produced by Vertex. This therapy involves using stem cells, which are “mother” cells with the ability to transform into various types of cells in the body.

Scientists took these cells and transformed them into cells similar to those in the pancreas, which can produce insulin. These new cells were infused (injected) into the vein that carries blood to the liver. The idea is that these cells will settle there and start producing insulin in the person's body, functioning as a “new pancreas”.

For this to work, participants had to take medications called immunosuppressants, which reduce the action of the immune system to prevent the body from rejecting the new cells.

New cell therapies for the treatment of type 1 diabetes are currently underway at Vertex.

The study involved 14 people with severe type 1 diabetes. Some received half the recommended dose and others received the full dose. All of them had a history of difficulty controlling their diabetes and had already suffered severe episodes of hypoglycemia.

The results were encouraging, with all participants starting to produce insulin, something that had not happened before the treatment. In total, 83% of the people who received the full dose were able to stop taking insulin on a daily basis up to a year after treatment.

All of the participants who received the full dose had more stable blood sugar levels, remaining within the range considered healthy most of the time. There were also no new cases of severe hypoglycemia after treatment among these people.

On the other hand, there were significant side effects: three participants had neutropenia, which is when the number of white blood cells (defense cells) drops significantly, increasing the risk of infections. Two people died during the study: one due to a serious infection (cryptococcal meningitis) and another due to the worsening of an existing neurological problem.

These results show that zimislecel has the potential to be a revolutionary treatment for type 1 diabetes, because it attacks the cause of the problem: the lack of insulin-producing cells.

However, there are still risks that need to be better understood, and more studies are needed to ensure the safety and effectiveness of this therapy before it can be approved for general use.

READ MORE:

Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes

Trevor W. Reichman, James F. Markmann, Jon Odorico, Piotr Witkowski, John J. Fung, Martin Wijkstrom, Fouad Kandeel, Eelco J.P. de Koning, Anne L. Peters, Chantal Mathieu, Leslie S. Kean, Bote G. Bruinsma, Chenkun Wang, 

Molly Mascia, Bastiano Sanna, Gautham Marigowda, Felicia Pagliuca, 

Doug Melton, and Michael R. Rickels 

The New England Journal Of Medicine. June 20, 2025

DOI: 10.1056/NEJMoa2506549

Abstract: 

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. 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 hypoglycemic 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 hemoglobin 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 prespecified. 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 preexisting neurocognitive impairment. All 12 participants in parts B and C were free of severe hypoglycemic events and had a glycated hemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter). Ten of the 12 participants (83%) had insulin independence and were not using exogenous insulin at day 365. 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. (Funded by Vertex Pharmaceuticals; VX-880-101 FORWARD ClinicalTrials.gov number, NCT04786262.)