Vertex Releases New Data on Its Potential Type 1 Diabetes Cure

This content originally appeared on Diatribe. It was reissued with permission.

by Annabrooks & Andrew Briskin

Important takeouts:

• VX-880 is an apical clinical trial stem cell therapy and is promising as a functional “treatment” for type 1 diabetes.
• New data show that study participants experienced significant improvements in reduced needs for A1C, glucose control, and insulin.
• The VX-880 trial was put on hold early in 2024 due to the deaths of two participants. Death is currently considered unrelated to research drugs.

Vertex presented new data this week in a thorough clinical trial, VX-880, as it is being hailed as a potentially innovative treatment for type 1 diabetes patients at EASD 2024 in Madrid. The trial, suspended earlier this year after the deaths of two participants, has now resumed and is actively adopted.

Although this study is still in its early stages, the results are promising. All 12 participants who received the full dose of VX-880 showed that A1c decreased by <7% and no longer developed severe hypoglycemia (hypoglycemia). Of the 12 participants, 11 reduced or completely eliminated the need for exogenous insulin (meaning injectable insulin that is not naturally produced by the body). Additionally, all participants experienced significant improvements in A1C, range time, and reduced need for insulin injection.

“At baseline, all enrollees had fairly insufficient control over a time range of less than 50%,” said Dr. Trevor Reichman, director of surgery for pancreatic and islet cell transplantation at the Ajura Transplant Centre in Toronto. “After all the complete doses of VX-880 have been improved, we can see them very quickly. And in a year or so, there is no evidence of severe hypoglycemic episodes, with the range exceeding 90%.”

Of the four participants who passed the 1 year mark after treatment, all achieved insulin independence and maintained A1c below 7%. This indicates that VX-880 may be the much-anticipated functional “treatment” for type 1 diabetes.

Before treatment with VX-880, all study participants produced zero insulin and had a history of severe and recurrent episodes of hypoglycemia. Three months after cell transplantation, participants showed successful insulin production to respond to glucose.

Death of participants: What happened?

Despite positive results early in the VX-880 trial, the apex ceased the study in January 2024 after two participants died. Neither death is thought to be related to the VX-880.

One participant died of meningitis after sinus surgery unrelated to the study. Reichmann explained that participants were given high doses of steroids before and after treatment (steroids are toxic to insulin-producing cells in the pancreas). Participants also used immunosuppressants, which is required following VX-880, but high-dose steroids also lower the immune system, leaving them vulnerable to infection.

Other participants died from traumatic brain injury following a motorcycle accident caused by a severe episode of hypoglycemia.

One participant remains unknown, while the other Brian Shelton, 66, was said to be the first person to have type 1 diabetes with VX-880. Shelton successfully produced his own insulin in 2021, six months after the treatment.

The trial is on track, but it is unclear whether a three-month suspension will affect the vertex timeline to complete the clinical trial.

What is VX-880 therapy?

VX-880, a type of experimental stem cell therapy, is intended to restore natural insulin production in patients with type 1 diabetes. This will result in a dramatic improvement in quality of life as people with illness no longer need insulin and do not need severe, sometimes life-threatening episodes of hypoglycemia.

Stem cell therapy, like VX-880, works by transplanting healthy insulin-producing cells into the body. If successful, new cells will replace non-functioning cells, eventually restoring insulin production.

Like those undergoing organ transplants, those treated with VX-880 should take immunosuppressants to prevent the immune system from rejecting new beta cells.

Due to the risk of infections associated with immunosuppressants, only those with apexual awareness of severe hypoglycemia are eligible for the apex trial. This is because these candidates have what they can get from this type of treatment given the risks associated with recognition of hypoglycemia.

The history behind the VX-880

Vertex first announced the development of the VX-880 in 2021. Data from the first two participants in the study were presented by Dr. James Markman, director of transplant surgery at Massachusetts General Hospital at the 2022 American Diabetes Association (ADA) conference.

In the first phase of the study, each participant was given a dose of half the estimated beta cells needed. A common practice in these types of studies is to start at half the expected dose and increase it as the trial progresses.

The results below show surprising improvements in A1C, time of range, and reduced insulin needs for each participant. For reference, ADA standard care recommends target times in the range of 70% (70-180 mg/dL). There is no “standard” insulin dose as daily insulin doses are determined by the healthcare provider based on each individual’s needs. To take this into consideration, we will examine some of the data from the two participants in detail.

Participant 1

Participant 2

The future of the VX-880

There was initial concern about the involvement of two participants with the VX-880 procedure, but Reichmann said there were no severe adverse events associated with islet cells themselves.

So far, the safety profile of VX-880 is similar to what would be expected given the use of immunosuppressant agents, surgical procedures to implant cells, and the patient’s medical history.

Following the recent positive results presented at EASD 2024, this study is not only ongoing, but is also recruiting more participants. Currently, there are 14 participants in the VX-880 trial, and Reichman wants to raise the number to 37 (see here for more information on how to register).

This data demonstrates the promising for VX-264, another novel apex stem cell therapy that does not require immunosuppression, which is currently being investigated in clinical trials.

When will this be available to more people with type 1 diabetes?

Unlike other interventions such as pancreatic transplantation and beta cell islet transplantation from human donors, VX-880 may be used on a much larger scale.

“Currently, in the US, there are only about 1,000 pancreatic transplants available, so supply is a serious issue,” Markman said. “One of the most important aspects of this work is that there may be an unlimited supply of beta cells for implantation.”

The results so far are exciting, but the research is still in its early stages. The current trial is expected to close in 2030 and additional studies with larger sample sizes should be followed. After all studies have been completed, the vertex must submit an application to the FDA before it is approved for use.

“It’s a groundbreaking job and it’s really moving forward for the field,” Markman said. “I can’t say exactly when this will be available, but it’s much closer to a functional treatment for type 1 diabetes than before this approach.”