The FDA Just Approved an Islet Cell Transplant for Type 1 Diabetes

In late June, the US Food and Drug Administration (FDA) approved a new cell therapy that can restore insulin production in patients with type 1 diabetes. Doniclecel (Lantidra) is the transplantation of insulin-producing islet cells from a deceased organ donor and is the first therapy approved in the United States.

This treatment can restore insulin secretion and reduce or even eliminate the need for exogenous insulin injections. However, its side effects can be extremely burdensome and limit its applicability.

Developed by Biotech Startup Celltrans, Lantidra is only applicable to adults with type 1 diabetes who face extreme management challenges. People who have experienced repeated severe hypoglycemic episodes and are unable to meet A1C targets. Severe hypoglycemia – Hypoglycemia events that are affected so much that the patient cannot treat himself – can cause seizures, coma, and death. For people with discomfort with hypoglycemia, the risk is particularly high as they do not reliably experience symptoms (such as tingling, hunger, dizziness) that act as a warning system for the body with hypoglycemia levels.

However, the FDA’s decision to validate a single business approach appeared to raise surprises among the community of experts who wanted to increase access to islet cell transplantation therapy.

A controversial decision

Until now, islet cell transplantation has not been available in the United States due to regulatory habits (except under the auspices of medical experiments): According to the National Organ Transplant Act of 1983, organ subparts are not counted as organs and are not covered by a network of rules and program rules that initiate organ transplantation. Instead, implantable islet cells are regulated as if they were drugs and are subject to high standards for accuracy and consistency that cannot be easily met. Many of the country’s prominent diabetes and transplant experts have denounced the situation (PDF).

A week before Lantidra’s approval, Sen. Mike Lee (R-UTAH) wrote a bill aimed at improving “outdated regulations on islet transplantation.” Instead, by approving Lantidra, the FDA is rapidly moving in a very different direction.

Isle-for-island supporters described the decision as “purely political” and argue that it will undermine patient safety and suppress innovation by granting the practice of islet cell transplantation to a single for-profit enterprise.

Reduce or eliminate insulin needs

The key study that led to Lantidra’s approval tested procedures in 30 patients. Those 30:

• 9 (30%) achieved insulin independence for over five years.
• 12 (40%) achieved insulin independence for 1-5 years.
• 4 (13%) achieved insulin independence in less than one year.
• 5 (17%) did not achieve insulin independence.

Although the experiments supporting Lantidra’s approval were small, there are also good data on related types of islet cell transplantation. Some transplant recipients require insulin therapy five years after implantation, but only side effects have been present and have not received insulin therapy following the procedure for many years.

Studies of islet cell transplantation also show that patients can improve glycemic control and reduce the use of exogenous insulin even if they cannot completely eliminate it.

Lantidra is rarely used

Lantidra is not widely used. Simply, sufficient donor cells are not available. Lantidra’s pancreatic islet cells deceased The organ donor places the hard cap on the number of steps that can be performed. According to the Health Resources & Services Administration, in 2022, 9,528 liver transplants were performed in the US, with only 4,111 heart transplants and 108 pancreatic transplants. Over 1 million Americans suffer from type 1 diabetes.

Although it is known that islet cell transplantation is effective, complications involved in both cell procurement and treatment of immunosuppressive drug patients limit the scope of Lantidra. However, for patients with deep needs (i.e., patients with extreme glucose management challenges and no awareness of hypoglycemia), islet transplantation can be a lifesaver.

The risks of immunotherapy

Lantidra is a high-risk treatment in itself, and is therefore limited to those who are most needed by the patient. The side effects are substantial, and recipients need immunosuppressants to protect donated islet cells from the body’s immune system, weakening the body’s defense against infection.

Speaking to James Shapiro, the surgeon who performed the world’s first islet cell transplant every day, he explained, “Immunosuppressive drugs are a major barrier to why we don’t transplant many cells today.” Risks include increased risk of cancer, increased risk of life-threatening infections, and side effects on the kidneys. It may also be toxic to the function of implanted cells and their ability to produce insulin. ”

In the trials that led to Lantidra’s approval, 87% of participants experienced at least one “severe” response, and 27% experienced at least one. Threatening life Side effects. Twenty-six participants experiencing an infection caused by immunosuppression combined 211 individual cases of infection. One subject died when the infection caused sepsis, leading to multiple organ failure.

Immunosuppression also significantly increases the risk of “malignant tumors” and increases the incidence of cancer. Lantidra recipients have seen a surge in risk of skin cancer, particularly skin cancer.

27% of study participants had to discontinue immunotherapy, which led to the inevitable destruction of transplanted islet cells. (The Holy Grail of Type 1 Diabetes Research is a treatment that employs a rich source of islet cells that can somehow escape from the immune system.

The procedure itself (participants undergo one or two surgeries) was also associated with complications. Approximately 10% of transplant recipients experienced anemia due to the need for surgery and blood transfusion. Surgery caused several cases of life-threatening liver laceration and bleeding and hematoma in or near the liver. The majority of participants reported symptoms such as vomiting, diarrhea, and abdominal pain.

In short, Lantidra carries a very serious risk.

Take home

The new islet cell transplant procedure, first approved in the US, could help some people with type 1 diabetes achieve insulin independence. The treatment named Doniclecel (Lantidra) will only be available to adults with a history of recurrent severe hypoglycemia and is not expected to become a mainstream treatment in a foreseeable future. Most people with type 1 diabetes are not candidates for Lantidra, but despite their highly burdensome side-effect profile, this procedure can be a lifesaver for others.

While it’s natural to praise the approval of a new treatment, some islet cell transplant experts are extremely skeptical of the FDA’s decision to grant exclusive rights to a single business, fearing that it will ultimately help Americans to make cell transplant therapy less accessible.