On Monday, Vertex made a monumental announcement. Their Phase 1/2 trial for VX-880 is converting to a Phase 1/2/3 pivotal trial, enrolling 50 total people.
It’s a huge first for type 1 diabetes (T1D). It’s the first time a scalable cure for some people with T1D is entering a Phase 3 clinical trial.
Let’s dive into what it means, how we got here, and what comes next.
What are cell therapies?
People with T1D are missing one big thing: the ability to produce insulin. In people with T1D, the immune system destroys the insulin-producing islets in the pancreas. If we can make insulin-producing cells and safely put them inside the body to replace the cells that were lost, we’ll have cured this disease.
Those are cell therapies—one of Breakthrough T1D’s biggest priorities, and what VX-880 is.
What is VX-880?
Vertex’s VX-880 is a stem cell-derived islet therapy. It uses stem cell-derived islets, which primarily contain beta cells, to restore the body’s ability to produce insulin. VX-880 requires the use of immunosuppressants to protect the transplanted cells from rejection.
The immunosuppressive regimen administered to accompany the infusion of cells is akin to those taken by recipients of solid tissue organ transplants. It has serious side effects. Finding alternative, less-toxic methods to prevent rejection is a key priority of Breakthrough T1D and next-generation products from Vertex.
The islets used in VX-880 derive from the Breakthrough T1D-funded work of Doug Melton, who first turned stem cells into insulin-producing cells in 2014.
VX-880 is not for the entire T1D community. It is only being tested in people with T1D with severe hypoglycemia unawareness and significant hypoglycemic episodes. Vertex is testing it only in this patient population.
The data has been eye-opening
Vertex has regularly shared data on how this therapy is working in people, and it’s been incredibly exciting.
The most recent update came at the European Association for the Study of Diabetes annual meeting in September 2024. The data presented included:
- All participants who received the full dose of the therapy are showing benefits, including:
- Insulin production as measured by C-peptide
- (C-peptide is a biomarker that shows endogenous insulin production)
- Elimination of severe hypoglycemia
- Significantly improved glucose control, with HbA1c’s less than 7% and >70% time in range.
- Insulin production as measured by C-peptide
- 11 out of 12 participants have reduced or eliminated the need for external insulin.
- All 4 participants who received the full dose of cells with a follow-up after more than one year met the primary endpoint of eliminating severe hypoglycemic events and achieved the secondary endpoint of insulin independence.
- The safety profile is consistent with the immunosuppressive regimen, infusion procedure, and complications of longstanding T1D.
These data show that VX-880 can restore insulin production in people with T1D. The primary endpoint for this study will be the proportion of study participants with insulin independence and absence of severe hypoglycemic episodes.
Stem cell versus deceased donor islets
Today, there is an FDA-approved islet transplant for individuals with T1D who are unable to achieve target HbA1c because of current repeated episodes of severe hypoglycemia called Lantidra. This therapy utilizes the Edmonton Protocol and relies on deceased-donor islets, which are taken from the pancreases of deceased organ donors. It can take up to three pancreases to harvest enough islets for one transplant.
There are simply not enough donor pancreases to gather enough islets for everyone with T1D. Stem cell-derived islets are the scalable solution to that problem.
These islets are manufactured in a laboratory and can be produced at scale. Vertex can make exponentially more cells in their facility than can be obtained via deceased donors—and they’ve broken ground on a manufacturing facility to make them.
What is a pivotal trial?
A therapy must undergo a series of clinical trials to assess its safety and efficacy before receiving FDA approval. The last stage is usually the Phase 3, or pivotal trial, which gathers the data required for an FDA submission.
This trial is a continuation of Vertex’s successful Phase 1/2 clinical trial.
Breakthrough T1D’s role
Breakthrough T1D has a collaborative partnership with Vertex and the leading researchers on the project, Drs. Doug Melton and Felicia Pagliuca, that goes back decades. Some key collaborations:
- Breakthrough T1D funded Doug Melton starting in 2004 to turn stem cells into insulin-producing cells. He accomplished this in 2014.
- In 2015, Melton founded Semma Therapeutics to turn these cells into curative therapies for T1D. In 2017, the T1D Fund made a catalytic investment in Semma.
- The T1D Fund also invested heavily in ViaCyte, which was acquired by Vertex in 2022.
Breakthrough T1D is thrilled this therapy is advancing. However, only a small subset of the T1D population will be authorized to use this therapy (assuming it gets FDA approval in the coming years). Our ultimate goal is a therapy that does not require the use of chronic immunosuppressants that the majority of people with T1D can use. (Vertex shares this goal).
We applaud Vertex for this achievement and we will continue our work to develop these strategies that will allow more people to use these potentially curative therapies.
Learn more about our work in cell therapies.
Other data shared
Vertex also shared that the Phase 1 trial for VX-264, their encapsulated stem cell-derived islet therapy, is progressing nicely and they expect to share data in 2025. Their gene-edited, hypoimmune islet therapy is still in development. These cells will not require the use of immune suppression.
What comes next?
Vertex has stated that its clinical trial is enrolling. We encourage anyone who is interested to visit clinicaltrials.gov and see if they are eligible to participate.
