FDA places hold on trial of novel cell therapy for type 1 diabetes
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The FDA has halted a clinical trial for an investigational stem cell-derived therapy for people with type 1 diabetes, according to an industry press release.
VX-880 (Vertex Pharmaceuticals), a novel investigational stem cell-derived pancreatic islet cell replacement therapy for people with type 1 diabetes with impaired hypoglycemia awareness and severe hypoglycemia, was placed on a clinical hold by the FDA due to insufficient data to support dose escalation.
“We are surprised by the clinical hold placed on the study,” Carmen Bozic, MD, executive vice president of global medicines development and medical affairs and chief medical officer for Vertex, said in a press release. “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. Further, the totality of the safety and efficacy data for all three patients dosed to date gives us high confidence in our benefit-risk assessment of VX-880 and its potentially transformative profile.”
As Healio previously reported, Vertex announced positive 90-day data for its first trial participant in October 2021. A person with type 1 diabetes treated with a single infusion of VX-880 at half of the target dose had “rapid and robust improvements” in fasting and stimulated C-peptide and HbA1c, as well as a decrease in exogenous insulin requirement at 90 days. In the year before treatment, the patient had five episodes of severe hypoglycemia, was treated with 34 U insulin per day and had undetectable levels of fasting and stimulated C-peptide. News reports described the participant as being the first person “cured” of diabetes after a cell infusion.
In new data released by Vertex, the participant from the October report achieved insulin independence at 270 days of follow-up with an HbA1c of 5.2%. A second participant receiving half of the target dose had an increase in stimulated C-peptide from an undetectable level at baseline to 202 pmol/L at 90 days and a decrease in HbA1c from 7.5% to 7.1% at 150 days with a 30% decrease in exogenous insulin use. Both participants were recommended to receive a full target dose in part B of the trial. A third participant had already received the full target dose and had trends indicative of increasing fasting C-peptide and improving glycemic control at follow-up on day 29 before the FDA’s decision to halt the trial.
No serious adverse events have been reported with VX-880, and most adverse events were mild or moderate, according to Vertex. The safety profile was consistent with the immunosuppressive regimen used in the study as well as the perioperative period.
According to the press release, Vertex plans to work with the FDA to understand the agency’s decision and answer questions with the hope of resuming the trial at a future date.
Perspective
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From the press release, it is hard to say why the FDA asked Vertex to halt the trial, and I have no inside information. A broad variety of trial design issues, outcome measures, safety assessment of the VX-880 stem cell preparation and the accompanying immunosuppressive drugs, and the sheer enormity of data output from the study could make the FDA concerned or at least slow down and take a deeper look at data in hand and patients currently in the trial.
For me, I am enthusiastic about Vertex’s approach, the quality of their team and of their science. It seems likely that the FDA is simply doing its due diligence. It also provides a public view of how complex and painstaking human clinical trials are. On one hand, people with and who advocates for type 1 diabetes all want potential treatments to move as quickly as humanly possible. Yet on the other hand, it is the investigators’ and FDA’s job to be sure there are no unnecessary risks to the current and future study participants.
The press release indicates several ways the diabetes stem field needs to move forward. Examples include encapsulating transplanted stem cells into a device that would protect the stem cells/beta cells from autoimmunity or alloimmunity, optimizing immunomodulatory drugs or drug cocktails that will control alloimmunity and autoimmunity, and creating designer stem cells that cannot be recognized by the type 1 diabetes recipient as foreign.
Other options are also possible. Mechanical artificial pancreas systems are already widely used and getting more sophisticated and miniaturized rapidly. A long-term vision here would be to create implantable devices like cardiac pacemakers. My group focuses on developing drugs — a pill or a shot — that are able to regenerate the beta cells that remain in most people with type 1 diabetes and type 2 diabetes. Artificial pancreas and beta cell regenerative drug therapies are making rapid progress as well. And, of course, there is still whole pancreas and pancreatic islet transplant, both in current clinical use, but limited by the paucity of organ donors.
Collectively, this is all good news for people with type 1 diabetes and type 2 diabetes: Both need more effective, affordable, easy to use therapies. We now are watching a serious horse race in progress.
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