In late June, the U.S. Food and Drug Administration (FDA) approved a brand new cell therapy that may restore insulin production in individuals with type 1 diabetes. Donislecel (Lantidra) is a transplant of insulin-producing pancreatic islet cells from deceased organ donors, the primary such therapy to be approved in the US.

The therapy can restore insulin secretion, reducing and even eliminating the necessity for exogenous insulin injections. Its unintended effects, nonetheless, may be extremely burdensome, limiting its applicability.

Lantidra, developed by the biotech startup CellTrans, is simply indicated for adults with type 1 diabetes with extreme management challenges: those that experience recurring severe hypoglycemic episodes and who also cannot meet A1C targets. Severe hypoglycemia — low blood sugar events wherein patients are so affected that they can not treat themselves — could cause seizures, comas, and death. The danger is very high for individuals with hypoglycemia unawareness, because they don’t reliably feel the symptoms (reminiscent of tingling, hunger, and dizziness) that serve because the body’s warning system for low blood sugar levels.

The FDA’s decision to validate a single business’ approach, nonetheless, has appeared to cause some consternation amongst a community of experts hoping to extend access to islet cell transplant therapy.

A Controversial Decision

Until now, islet cell transplants have been unavailable in the US (except under the auspices of a medical experiment) due to a regulatory quirk: In keeping with the National Organ Transplant Act of 1983, subparts of organs don’t count as organs and are usually not covered by the network of rules and programs governing organ transplantation. As a substitute, transplantable islet cells are regulated as in the event that they were drugs, subjecting them to high standards for precision and consistency that they can not easily meet. Lots of the nation’s distinguished diabetes and transplantation experts have decried the situation (PDF).

Just one week before Lantidra’s approval, Senator Mike Lee (R-Utah) authored a bill to intended to enhance the “outdated regulation of islet transplantation.” As a substitute, by approving Lantidra, the FDA has rapidly gone in a really different direction.

Advocates with the Islets for US Collaborative described the choice as “purely political,” alleging that it could compromise patient safety and stifle innovation by granting a monopoly on the practice of islet cell transplantation to a single for-profit company.

Reducing or Eliminating Insulin Needs

The pivotal studies that led to Lantidra’s approval tested the procedure in 30 patients. Of those 30:

• 9 (30 percent) achieved insulin independence for greater than five years.
• 12 (40 percent) achieved insulin independence for one to 5 years.
• 4 (13 percent) achieved insulin independence for lower than one 12 months.
• 5 (17 percent) didn’t achieve insulin independence.

Though the experiment supporting Lantidra’s approval was small, we even have good data on related varieties of islet cell transplants. Some transplant recipients have remained freed from insulin therapy for a few years following the procedure, with only minor unintended effects, although most patients require some insulin therapy five years after their transplant.

Studies of islet cell transplantation also show that patients improve their blood sugar control and might reduce their usage of exogenous insulin, even when they can not wholly eliminate it.

Lantidra Will Be Used Only Rarely

Lantidra won’t be used widely: There simply aren’t enough donor cells available. Islet cells for Lantidra are harvested from the pancreas of a deceased organ donor, putting a tough cap on the variety of procedures that would possibly be performed. In keeping with the Health Resources & Services Administration, there have been 9,528 liver transplants conducted in the US in 2022, 4,111 heart transplants, and only 108 pancreas transplants. Over 1 million Americans have type 1 diabetes.

While we all know that islet cell transplantation is effective, the complications involved with each sourcing the cells and treating patients with immunosuppressive drugs will limit Lantidra’s reach. But for patients with a profound need — those with extreme glucose management challenges and hypoglycemia unawareness — islet transplantation may very well be a lifesaver.

The Dangers of Immunotherapy

Lantidra can even be limited to the patients in biggest need of help since it is itself a high-risk treatment. The unintended effects are considerable, and recipients will need immunosuppressive drugs to guard the donated islet cells from the body’s immune system, weakening the body’s defense against infection.

When Diabetes Every day spoke to James Shapiro, MD, the surgeon who performed the world’s first islet cell transplants, he explained that “immunosuppressive drugs are the massive barrier for why we don’t do large numbers of cell transplants today. The risks include increased risk of cancers, increased risk of life-threatening infections, unintended effects on the kidney, and so they will also be toxic to the functioning of the transplanted cells and their ability to make insulin.”

Within the trials that led to Lantidra’s approval, a whopping 87 percent of participants experienced a minimum of one “severe” response, and 27 percent experienced a minimum of one life-threatening hostile response. The 26 participants to experience infections attributed to immunosuppression totaled 211 separate incidents of infection. One subject died when an infection caused sepsis, resulting in multi-organ failure.

Immunosuppression also greatly increases the chance of “malignancy,” resulting in high rates of cancer. Lantidra recipients saw their risk of skin cancer skyrocket, specifically.

Twenty-seven percent of trial participants needed to discontinue their immunotherapy, which leads inescapably to the destruction of their transplanted islet cells. (The holy grail of type 1 diabetes research is a therapy that employs an abundant source of islet cells that may one way or the other escape the immune system, obviating the necessity for immunotherapy.)

The procedure itself (participants undergo either one or two surgeries) was also related to complications. About 10 percent of transplant recipients experienced anemia resulting from surgery and required blood transfusions. The surgeries caused one life-threatening liver laceration and several other cases of hemorrhaging and hematoma on or near the liver. A majority of participants reported symptoms reminiscent of vomiting, diarrhea, and abdominal pain.

Briefly, Lantidra entails very significant risks.

Takeaways

A brand new islet cell transplant procedure, the primary approved in the US, has the potential to assist some individuals with type 1 diabetes achieve insulin independence. The therapy, named donislecel (Lantidra), will likely be available only to adults with a history of recurrent severe hypoglycemia and just isn’t expected to grow to be a mainstream treatment within the foreseeable future. Most individuals with type 1 diabetes won’t be candidates for Lantidra, however the procedure may very well be a lifesaver for others, despite a really burdensome side effect profile.

While it seems natural to applaud the approval of any latest treatment, some islet cell transplantation experts are very skeptical of the FDA’s decision to grant exclusive rights to a single business, fearing that it’ll ultimately serve to make cell transplant therapies less accessible to Americans.