June 30, 2023 – Treatment of intractable type 1 diabetes with transplanted pancreatic cells is moving forward on two fronts, with one product recently approved and the other advancing in a clinical trial.
Type 1 diabetes is an autoimmune disease in which the insulin-producing beta cells of the pancreas (often just called “islets” because they are located in the islets of Langerhans in the pancreas) are destroyed by the body’s own immune responses. People with the condition take insulin via syringes or a pump to stay alive and must also regularly measure their blood sugar levels and adjust their insulin.
But some people with type 1 diabetes often have very low blood sugar (hypoglycemia) and may not feel the symptoms, such as shaking and sweating, that signal a drop in blood sugar. These people (known as hypoglycemia unaware) are the only candidates for cell islet therapy, in part because they must also take medication to suppress their immune system to prevent rejection—the same as is required for all other transplanted organs, such as a kidney – and that carries risks too. Researchers are working to end the need for immunosuppressants.
The FDA on Wednesday approved Lantidra, a treatment made from pancreatic islet cells from deceased donors who have, or whose families have, agreed to donate their organs after their death. Lantidra, made by CellTrans, is approved for people with type 1 diabetes who cannot achieve target blood sugar levels with insulin.
In clinical trials with Lantidra, 21 of 30 patients did not need to take insulin for at least 1 year, while 10 were still insulin independent more than 5 years after treatment. But in five patients it did not work at all.
Meanwhile, in an early clinical trial of another type of pancreatic islet cell made from stem cells, Vertex Pharmaceuticals’ VX-880, two people with type 1 diabetes and severe hypoglycemia have been able to stop taking insulin completely for at least a year, and three others are going in that direction. These findings were presented June 23 at the annual American Diabetes Association’s Scientific Sessions.
Both types of islets are infused into the portal vein, which carries blood from several organs to the liver, as well as insulin from the pancreas to the liver in people without type 1 diabetes.
“For decades now, the promise of pancreatic islet transplantation as a treatment for a small subset of those with the most difficult-to-control type 1 diabetes—and particularly those with frequent and severe hypoglycemia—has faced two major obstacles,” said David M. Harlan, MD, co-director of the University of Massachusetts Diabetes Center of Excellence.
“One is an insufficient supply of islets to transplant, and two, the sometimes toxic immunosuppression required to prevent the transplanted islets from immune rejection,” he said.
The latest results with VX-880 “hold the promise of overcoming both hurdles by allowing stem cell-derived islets to be grown in the lab, thereby opening the possibility of a virtually infinite supply,” said Harlan, who is also a professor of medicine at the University of Massachusetts Chan Medical School in Worcester.
There were no major safety concerns in the VX-880 study, which is now being expanded to include more people in several European countries as well as in the United States.
With Lantidra, side effects included nausea, fatigue, anemia, and stomach pain. Most people in the trial had at least one serious side effect, either from the IV procedure into the portal vein or from the immunosuppressive medications. In some cases, these events required the person to stop using these medications and lose the function of the transplanted cells.
“These adverse events should be considered when assessing the benefits and risks of Lantidra for each patient,” the FDA said in a statement.