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A stem-cell treatment restored insulin production and glucose control in two patients with type 1 diabetes (T1D), a researcher reported.

Following a 40-year history of T1D riddled with complications, a 64-year-old man received a single infusion with the investigational treatment VX-880 at a half target dose, said James F. Markmann, MD, PhD, of Massachusetts General Hospital in Boston, during the American Diabetes Association (ADA) annual meeting.

Developed by Vertex Pharmaceuticals, the treatment works as an allogeneic stem cell-derived, fully differentiated, pancreatic islet cell replacement therapy.

By day 90 of the phase I/II clinical trial, the patient experienced a slew of improvements in measures of pancreatic islet function and glycemic control:

• Fasting C-peptide level: undetectable at baseline vs 280 pmol/L at day 90
• Peak stimulated C-peptide level with mixed meal tolerance test: undetectable at baseline vs 560 pmol/L at day 90
• HbA1c: 8.6% at baseline vs 7.2% at day 90

The patient's daily insulin dose also dropped from 34 units/day down to only 2.9 units/day, representing a 91% decrease in daily exogenous insulin use. Moreover, glycemic variability dropped from 41.8% to 27.5% as measured by a continuous glucose monitor. Time spent in target range -- 70 to 180 mg/dL -- increased from 40.1% to 63.2%.

These measures continued to improve by day 150, Markmann said. At this time point, fasting C-peptide levels increased to 404 pmol/L and HbA1c dropped down to 6.7%. Time spent in target range also increased to 81.4%.

By day 270 after the initial half dose infusion, this patient achieved complete insulin independence, an HbA1c of 5.2%, and spent 99.9% of time in target range.

"This is the first-in-the-world administration of stem cell-derived islets in this manner where they're infused into the liver," Markmann said during an ADA press conference. "In the experience with cadaveric islets, the only site that was effective at really gaining full glycemic control was the liver. And so this was the first attempt to really have an important impact on the patient's glycemic control."

"This does bring hope that's closer than it was before," he added. "This is, I think, groundbreaking work and a real leap forward for the field."

The second patient in the study, who is 150 days out of the initial infusion, saw similarly promising results. This patient increased time spent in range (35.9% at baseline to 51.9% at day 150), lowered HbA1c (7.5% to 7.1%), and decreased daily insulin need (25.9 units to 18.2 units).

The stem cell treatment was administered as a single infusion at half the target dose. The infusion was delivered into the hepatic portal vein and required chronic immunosuppressive therapy in order to protect the islet cells from immune rejection.

"The patient had received an immunosuppression regimen that had been developed for the phase III clinical islet transplant consortium trials that had finished a couple years ago," Markmann elaborated. "It consisted of completion of lymphocytes at induction and then a maintenance regimen with two standard agents that we use in kidney transplant patients and others all the time -- that's a regimen that we found to be generally well-tolerated."

He pointed out that immunosuppression isn't for all patients, and therefore they're only targeting patients for whom the risk/benefit considerations make sense.

"This is part one of a two-part problem," he noted. "Part one is to have a reliable, consistent, effective cell therapy. The second part is to have an approach that doesn't require immunosuppression."

Right now the patients being targeted are patients with an absence of endogenous insulin production, impaired awareness of hypoglycemia and severe hypoglycemic events. Providing an update on patient 1, Markmann said he is "doing great" and "probably the most appreciative patient I've ever met."

"His life was being destroyed by diabetes. He couldn't work, he crashed his motorcycle from lows, and really was tremendously appreciative that he could participate," he added. "These people really suffer and this, I think, brings hope to them."

"If we had a way to transplant the cells without the need for immunosuppression, then it could be really widely available," Markmann continued. "That's one of the great opportunities hopefully in the future, since these cells can be made in unlimited quantities."

He explained that this is only the first step in a three-part clinical trial -- acting as the proof-of-concept "Part A" of the phase I/II study. So far, a third patient in Part B of the study has received a full target dose of VX-880, which was well-tolerated. Following these positive results at the half target dose, there are plans in place for a dose-escalation study, followed by a full-dose study. Five patients are planned to receive the full target dose in Part B.

However, last month the FDA placed a clinical hold on the study, stating that there was insufficient information to support the dose-escalation phase.

"The team at Vertex is working with the FDA to address the issues that were brought up regarding having enough justification to do the dose escalation," Markmann said, adding that his team is hoping for a quick resolution.

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