Exciting updates from Vertex stem cell-based therapy clinical trials

A large area of cure-based T1D research is investigating stem cell-based therapy. The goal of this approach is to use stem cells as a renewable source of insulin-producing cells which, when transplanted, would replace beta cells that are destroyed in a person with T1D, thereby allowing them to produce insulin again. This would lessen or eliminate the amount of external insulin required by someone living with T1D (either by injection, pen, or pump) for months or even decades.

Challenges to bringing this approach to the clinic include identifying the appropriate stem cell source and ensuring transplanted cells function well and are not rejected by the recipient’s immune system.

In February 2021, Vertex announced the launch of a clinical trial for VX-880, a stem cell-derived therapy people with T1D. On October 18, 2021, the company announced that the first trial participant to receive VX-880 now needs 91% less insulin 90 days after receiving an infusion of these stem cells – and at just half the target dose.

The success seen with just half the target dose is exciting as it suggests a lower level of this therapy may still yield positive results.

However, it is important to be cautious at the same time, as this result has thus far only been demonstrated in a single individual.

How is success of this clinical trial measured?

VX-880 is being tested in people with T1D who have severe hypoglycemia and impaired hypoglycemia unawareness. The treatment requires immunosuppression, as the transplanted cells do not have any protection from the immune system. This requirement limits the patient population who can be enrolled in the trial.

The primary goal of this phase 1/2 trial is to assess safety, although efficacy will also be measured. Vertex is evaluating efficacy by measuring a few key metrics. This includes measuring C-peptide levels—a marker that directly indicates insulin production by beta cells. The participant in this study had no detectable C-peptide at all pre-infusion. 90 days after infusion of the VX-880 cells, the participant had both fasting and stimulated C-peptide, which directly indicates the presence of basal and glucose-responsive insulin secretion. In other words, the person was making some of their own insulin.

Treatment with VX-880 also led to a significant reduction in HbA1c, improving from 8.6% to 7.2% without severe hypoglycemic events. Even more impressive is that this lower HbA1c was achieved with a 91% daily reduction in insulin administration.

The study also demonstrated patient safety, as during the first 90 days, the participant did not experience any severe adverse events considered related to VX-880. This is important as immunosuppressive drugs do come with potential side effects.

JDRF’s Role

JDRF’s involvement can first be traced back to 2000, when Douglas Melton, Ph.D. was given a JDRF grant to make insulin-producing beta cells from stem cells—which he did in 2014.

Since then:

  • In 2015 Dr. Melton founded Semma Therapeutics to develop these stem cells into curative therapies for T1D.
  • In 2017, the JDRF T1D Fund made a significant investment in Semma.
  • In 2019, Vertex acquired Semma for almost $1 billion USD.
  • In March 2021, VX-880 received fast-track designation from the US Food and Drug Administration (FDA).

JDRF globally has prioritized stem cell therapy as a potential cure-based therapy and will continue to investigate and fund the most promising research.

What does this mean for Canadians with T1D?

For VX-880 to be broadly accessible to people with T1D, the cell product needs to both work and function without or with minimal immunosuppressive therapies.

The next step is approval to run clinical trials that could eliminate the need for immunosuppressives.

In the meantime, Vertex will continue their clinical trial for people with T1D who have severe hypoglycemia and are currently enrolling in several sites in the United States.

JDRF Canada will continue to monitor results and provide updates as they are made public.

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