June 30, 2023 – The treatment of difficult-to-treat type 1 diabetes with transplanted pancreatic cells is progressing on two fronts: one product has been newly approved and the opposite is making progress in a clinical trial.
Type 1 diabetes is an autoimmune disease through which insulin-producing beta cells within the pancreas (often called “islet cells” because they're situated within the pancreas' islets of Langerhans) are destroyed by the body's own immune response. People with the disease must inject or pump insulin to remain alive, and must usually check their blood sugar levels and adjust their insulin dose.
However, some individuals with type 1 diabetes often have very low blood sugar levels (hypoglycemia) and don't experience the symptoms that signal a drop in blood sugar, akin to shaking and sweating. These people (called unconscious hypoglycemia) are the one candidates for islet cell therapy, partly because additionally they have to take drugs to suppress their immune systems to stop rejection – as is required for every other transplanted organ, akin to a kidney – and this also carries risks. Researchers are working to finish the necessity for immunosuppressants.
The FDA on Wednesday approved Lantidra, a drug produced from pancreatic islet cells from deceased donors who, or whose families, have agreed to donate their organs after they die. Lantidra, made by CellTrans, is approved for individuals with type 1 diabetes who cannot control their blood sugar levels with insulin.
In clinical trials of Lantidra, 21 of 30 patients didn't have to take insulin for at the very least a 12 months, while 10 were still insulin independent greater than five years after treatment. However, in five patients, the treatment had no effect in any respect.
Meanwhile, an early clinical trial of one other kind of stem cell-derived pancreatic islet cell, Vertex Pharmaceuticals' VX-880, has helped two individuals with type 1 diabetes and severe hypoglycemia to completely stop using insulin for at the very least a 12 months, and three more are on the right track to accomplish that. The results were presented June 23 on the American Diabetes Association's annual Scientific Sessions.
Both forms of islet cells are infused into the portal vein, which in people without type 1 diabetes carries blood from several organs to the liver and likewise carries insulin from the pancreas to the liver.
“For decades, islet transplantation as a treatment for a small subset of the most difficult-to-control type 1 diabetes patients – and particularly those with frequent and severe hypoglycemia – has faced two major hurdles,” said David M. Harlan, MD, co-director of the Diabetes Center of Excellence on the University of Massachusetts.
“First, there are not enough islet cells for transplantation, and second, sometimes toxic immunosuppression is required to prevent immune rejection of the transplanted islet cells,” he said.
The recent results with VX-880 “hold the promise of overcoming both hurdles because stem cell-derived islets can be grown in the laboratory, opening the possibility of a virtually unlimited supply,” said Harlan, who can be a professor of medication on the University of Massachusetts Chan Medical School in Worcester.
No major issues of safety were identified within the VX-880 study, which is now being expanded to incorporate more people in several European countries and the United States.
Side effects of Lantidra included nausea, fatigue, anemia and abdominal pain. Most study participants had at the very least one serious side effect, either resulting from the intravenous administration into the portal vein or to the immunosuppressive drugs. In some cases, patients needed to stop taking the drugs and the transplanted cells lost their function.
“These side effects should be considered when evaluating the benefits and risks of Lantidra for each patient,” the FDA said in an announcement.