Type 1 diabetes research progress: New stem cell therapy can reduce need for insulin by 91%

Professor Doug Melton, who successfully produced insulin-producing beta cells from stem cells

The first person to receive a new stem cell-derived therapy for type 1 diabetes, VX-880, has been found to need 91% less daily insulin 90 days after receiving just half the target dose.

This week pharmaceutical company Vertex announced the results of the clinical trial, which could lead us closer to developing cures for type 1 diabetes. The trial is built upon research developments funded by JDRF that made global headlines in 2014.

How might stem cell therapy lead to cures?

Curing type 1 diabetes requires a renewable source of beta cells that can be produced in the laboratory—and they must work. Once placed into the body, they need to be up to the task of restoring insulin production in people and automatically regulating blood-glucose levels. Although Vertex only shared the data for one individual, the company’s data shows that VX-880 can do this.

However, this clinical trial is in an extremely limited patient population—people with severe hypoglycemia. The cells in VX-880 do not have any sort of protection from the immune system, which is why immunosuppressive drugs are required. For this therapy to be applicable for the entire type 1 diabetes population, the cells need to both work and function without or with minimal immunosuppressive therapies.

What does the data show?

There are few things to keep in mind while assessing the data. One is that these are only results from a single person. Data are needed from many more to fully evaluate the potential of this therapy. The second is that this person only received half the target dose of cells.

How well this therapy works is assessed using a few key measurements. One way is by measuring C-peptide levels—a marker that directly indicates whether insulin is being produced or not (or how much). The patient in this study had no detectable C-peptide at all before receiving the new cells, showing that their pancreas wasn’t producing insulin. After infusion of the cells, the patient had both fasting and stimulated C-peptide, which directly means that they are able to produce a background level of ‘basal’ insulin and that they could make more insulin on demand.

The patient also saw a significant reduction in their HbA1c, improving from 8.6% to 7.2% without severe hypoglycemic events (an amazing result, considering this therapy is only being tested in people with severe hypoglycemia). This lower HbA1c was achieved with a 91% daily reduction in insulin administration.

Another key metric to look at is safety. These therapies are of no use if they are not safe. During the first 90 days, this patient did not experience any severe adverse events that were considered related to VX-880. Individuals in this clinical trial are on a standard regime of immunosuppressive therapies, which do come with side effects.

Breakthrough T1D UK’s role

This latest progress follows research developments funded by JDRF.

In 2000, JDRF gave a grant to Professor Doug Melton, to make insulin-producing beta cells from stem cells – which he did in 2014. Professor Melton then founded a company, Semma Therapeutics, to develop these cells into curative therapies for type 1. He named the company Semma in honour of his two children who live with type 1 diabetes. The JDRF T1D Fund then invested in Semma, which was later acquired by Vertex. In March 2021, VX-880 received fast-track designation for the Food and Drug Administration (FDA). The FDA’s Fast Track programme is designed to accelerate the development and review of new medicines.

What comes next?

Vertex will continue the clinical trial which is currently underway in the United States. The company plans to file an Investigational New Drug application with the FDA in 2022 for their encapsulated islet cell program, which could eliminate the need for immunosuppressive drug treatment and, if used successfully in conjunction with VX-880, could be a major step forward in finding type 1 diabetes cures.