A trial of a new stem cell-based therapy for type 1 diabetes has been halted by the U.S. Food and Drug Administration (FDA) due the agency’s judgment that there is insufficient data to support escalating doses of the therapy going forward, according to an announcement from the company developing the therapy, Vertex Pharmaceuticals.
The new investigational therapy, known as VX-880, is intended as a replacement therapy for pancreatic islet cells — the insulin-producing cells that are targeted and destroyed by the body’s own immune system in type 1 diabetes. While islet cell transplants have been performed countless times around the world — and tend to be successful at letting people with type 1 diabetes use less insulin, or no insulin at all, while greatly improving their blood glucose control — there are a few reasons why the procedure is not a mainstream practice in the United States. One reason is that the supply of islet cells available for transplantation is limited — but this is also true in countries where the procedure is more common. Another issue is that most common version of the procedure requires taking immune-suppressing drugs so that the body doesn’t attack the transplanted islet cells, which can make people more susceptible to infections and other health problems like cancer — but again, this is a risk that exists in every country where the procedure is performed, although researchers are studying ways to potentially eliminate the need for these drugs.
The main reason, in fact, why islet cell transplantation isn’t more common in the United States is that the U.S. Food and Drug Administration (FDA) has the authority to regulate the transplanted cells as a biologic therapy, rather than treating them like a transplanted organ. This means that islet cell transplantation can only be performed in an experimental context in the United States, unlike in many countries where it can be offered as a standard procedure for certain cases of type 1 diabetes. So especially in the United States, there is potential demand for an approved biologic therapy — lab-created islet cells — that can work the same way as pancreatic islet cells taken from a human donor. Vertex’s VX-880 falls into this category, and the treatment has already been shown to restore insulin production in the first person who received the experimental treatment.
VX-880 placed on clinical hold by FDA
But in spite of further signs of the treatment’s effectiveness since then, the FDA doesn’t believe that the data supports continuing studies of VX-880. According to Vertex’s latest announcement, two study participants with type 1 diabetes — both of whom suffered from severe hypoglycemia (low blood glucose) and hypoglycemia awareness — received half of the target dose of VX-880 as part of the initial phase of the study, known as Part A. The first participant experienced insulin independence on day 270 following this treatment, with an A1C level (a measure of long-term blood glucose control) of 5.2% — indicating normal blood glucose control, as is typically seen in people without diabetes. The second participant, who started the treatment later, has seen reductions in insulin use through day 150. Taken together, these results prompted Vertex to start a third participant on a full dose of VX-880, and this person has ben followed for 29 days following the treatment.
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Vertex noted its announcement that there have been no reports of serious adverse reactions in any of the participants, and that reported side effects have been consistent with the immune-suppressing drugs that they are taking. But upon reviewing the data so far, the FDA placed the study on a clinical hold based on its determination that there is “insufficient information to support dose escalation with the product.”
“We are surprised by the clinical hold placed on the study,” said Carmen Bozic, MD, chief medical officer at Vertex, in the company’s announcement. “The results from the first two patients treated with half the target dose establish proof-of-concept by demonstrating that VX-880 can restore glucose-regulated insulin production and improve glycemic control. Indeed, achievement of insulin independence by the first patient is a landmark milestone.” Bozic emphasized that the company is “committed to working with the FDA to understand and address their questions, so that the trial can resume at U.S. sites as soon as possible.”