Stem-cell derived islet cell therapy successful in T1D

Type 1 diabetes

By Mardi Chapman

25 Jun 2024

Professor Piotr Witkowski

The curative potential of stem-cell derived, fully differentiated and insulin-producing islet cell transplantation has been demonstrated in patients with type 1 diabetes complicated by impaired awareness of hypoglycaemia and severe hypoglycaemia.

Speaking at the 2024 ADA Scientific Sessions, Professor Piotr Witkowski presented data from the phase 1-2 FORWARD study  which involved 12 patients who received the full dose in a single infusion of the investigational product VX-880 (Vertex Pharmaceuticals).

Professor Witkowski, Director of the Pancreatic and Islet Transplant Program at the University of Chicago, said all 12 participants demonstrated engraftment of islets with clinically meaningful endogenous insulin (C-peptide) production and improved glucose levels by day 90.

As well, all participants achieved a reduction in HbA1c to <7%, all had elimination of severe hypoglycaemic events, and all had a reduced requirement for insulin therapy.

“Out of 10 patients who have already passed six months of follow-up, seven patients remain insulin independent,” he said in the first joint ADA and International Pancreas & Islet Transplant Association (IPITA) session.

Professor Witkowski said all participants also demonstrated improvement in CGM metrics and achieved >70% time-in-range and reduction of time-below and time-above-range.

“Three patients who already achieved one year follow-up met the primary endpoint, so they were free of severe hypoglycemia unawareness and severe hypoglycemic episodes and have improved glucose control, and they also met the secondary endpoint with all three patients achieving insulin independence.”

He said all patients experienced adverse events, mostly mild-moderate severity, and all related either to immunosuppression therapy, the infusion procedure or complications from long standing type 1 diabetes.

“None of the severe adverse events were related to the islet cells,” he said.

Two deaths in the participants were reported – one due to cryptococcal meningitis following elective sinus surgery, high dose steroids before and after surgery and immunosuppression medication; the second death due to progression of preexisting neurocognitive impairment sustained during a motorcycle accident caused by a severe hypoglycaemic episode before study enrolment.

The study has been expanded to enrol 20 additional participants in order to accelerate consideration for registration of VX-880 as a drug and the standard of care therapy.

Professor Witkowski told the meeting that while immunosuppressive therapy is the current strategy to protect the islet cells from the immune system after transplantation, other strategies are emerging.

They include separating the islets from the host immune system via a barrier and gene editing to create cells which are less immunogenic.

Early studies are underway to evaluate the safety, tolerability and efficacy of encapsulating islets in an immunoprotective device implanted in the abdominal wall [link here] and allogeneic pancreatic endoderm cells genetically modified using CRISPR [link here].

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