Why Experts Are Blasting the FDA’s Approval of a New Type 1 Diabetes Cell Therapy

That seemed like good news: years after it became available in other countries, it was powerful. Cell therapy for type 1 diabetes Approved in the US in June. It is offered This is the first method in which American patients receive transplantation of insulin-producing islet cells outside the boundaries of clinical trials.

However, the experts who helped invent and develop islet transplant surgery are not celebrating it. Instead, they criticize the U.S. Food and Drug Administration (FDA) for choosing to regulate transplanted islet cells as drugs rather than organs. As a result, a single private company will become the island’s only approved American supplier for transplants.

“I don’t understand what the rationale is.” Camilo Ricordi, Marylandhonorary director of the Diabetes Institute regarding the decision to regulate organs as drugs rather than organs. “There is no scientific basis for that.”

Piotr Witkowski, MD, PhDdirector of the Pancreatic and Islet Transplant Program at Uchicago, said: “There’s one voice in the transplant community. No one who understands transplant regulations supports this (regulation), in the state or anywhere in the world.”

Every day in comments on diabetes, the FDA stood behind the decision to approve treatment, but the island had not addressed the bigger question of whether it should be regulated as a drug. Celltrans, an FDA-approved business for distributing islands for porting, did not respond to multiple requests for comment.

Islet cell transplantation

Islet cell transplantation is a sophisticated treatment for type 1 diabetes. Simply put, doctors take donor islets (clusters of pancreatic cells containing insulin-producing beta cells) and inject them into the diabetic patients, usually liver. If successful, the patient can either completely discontinue insulin use or significantly reduce their reliance on insulin.

Some transplant recipients Insulin therapy has not been present for many years Following the procedure, anti-rejection drugs carrying their own serious risk are required to protect new cells from the body’s immune system.

The experiment is underway Assessing the use of laboratory-grown islet cellsHowever, today, these transplanted islet cells must be collected from the pancreas of deceased organ donors. Such donor cells are lacking, limiting the number of surgeries that can be performed. However, for patients with disastrous needs, such as extreme glucose management challenges and patients without hypoglycemia, islet transplants can be a lifesaver.

Regulation confusion

Shortly after the first successful islet transplantation in 1993, the FDA announced that it would treat the implanted islets as if they were the case. medicine Not an organ or subpart. This decision has confused experts. “We are the only country that imposes this kind of regulation,” says Dr. Ricordi, who developed it in 1988. Islet cell separation technology This makes porting possible.

The problem is that the organ donor’s body island may not be able to meet criteria for accuracy and consistency of the drug components. Like other organs, islet cells cannot accurately assess pre-transplant infertility, purity, or efficacy. Even if possible, the nonprofit research hospitals that developed the treatment do not have the resources to meet the FDA’s expectations.

“Academic institutions have not been able to invest millions of dollars in jobs. bla (Application for a Biology License),” says Ricordi.

Over the years, Dr. Witkovsky, Ricordi and many of their colleagues campaign It was named “Isle of Our Cooperation” to change the FDA’s thinking. “We have told the FDA that patient safety is at risk if the island is approved as a drug and is dispersed solely by for-profit organizations. The island needs to be regulated like any other organ for transplant,” Witkowski says.

Universities and nonprofit hospitals could not justify the costs, but the biotechnology company named Cell transformer We raised enough funds to jump over the FDA hoops. However, it was initially unclear whether Celtran could overcome the inevitable problems of consistency unique to human organs.

Between Hearing in April 2021the FDA Advisory Panel evaluated the results of Celltrans clinical trials. Witkowski said the presentation confirmed what porting experts already know. you can’t Meets the FDA’s stated standards for drug manufacturing. Naturally, the FDA found no correlation between the quality measures of islands and the clinical efficacy measures.

“The FDA has clearly outlined why Celltrans failed,” claims Ricordi. Still, the majority of independent experts on the panel agreed that treatment has a “overall beneficial risk profile for some patients with type 1 diabetes.”

Panel approval did not quickly follow Sertran’s therapy towards approval. This procedure sat in the regulated limbo for about two years.

Surprising approval

Witkowski felt like the island for US collaboration had finally reached somewhere in June. Senator Mikeley (R-UTAH) wrote legislative efforts to amend regulations and pave the way for legitimate islet transplants in America. Island act He promised to “moving the island into a more appropriate regulatory framework.” But Witkowsky’s optimism was short-lived.

A week after Senator Lee announced the bill, the FDA announced it had approved Celtlan’s dead island. The sauce for the new island will be named Doniclecel (Lantidra). The island cooperation for us responded with doubt, Statement The move “significantly complicated the path to passing the Island Act and the path to implementing important regulatory updates.”

Celltrans had to spend millions to file a successful BLA, but critics argue that the business didn’t actually develop anything new. a 2021 letter in International transplantation “It’s just a new name for allografting of islets,” Lantidra said.

Witkowski agrees. “They invented nothing. They didn’t change anything. It’s an unchanged human organ, but they call it a drug and sell it as a drug.”

Lantidra is currently the only FDA approved source of islets for transplantation for the treatment of type 1 diabetes.

Islet Transplantation and Risks

Islet cell transplantation has great potential to treat type 1 diabetes. In the most important trial of Lantidra, conducted at an academic transplant center following all known protocols, 30% of participants achieved insulin independence in at least 5 years.

However, islet transplantation mainly involves side effects profiles with potent immunosuppressive drugs needed to protect new cells. A whopping 87% of Lantidra exam participants experienced at least one “severe” response, and 27% experienced at least one Threatening life Side effects. Among 30 patients, there were 211 infection cases. The infection caused sepsis, multi-organ failure, and another subject died when he developed a life-threatening liver laceration.

Witkowski says, “This wasn’t a shock to us.” The risks inherent in islet transplantation are important. This is part of the reason why this procedure is limited to patients with the deepest glucose management challenges.

However, Witkowski worries that Lantidra’s risk profile could be even worse in the real world. Because distributing it as a drug overturns the chain of responsibility that helps keep organ transplants safe.

Traditionally, islet transplant surgeons take ownership of all aspects of the surgery. Continuously monitor organ selection and evaluation, surgical operations, and patient monitoring.

“I take responsibility for doing everything,” Witkowski says. “I choose the donor and everything. If there’s anything wrong, it’s at me and my transplant center and I have to disclose the results.”

But by distributing Lantidra as a drug, “surgeons lose control of the product. They have no choice. They have to take what they are given.”

Celltrans can choose to sell Lantidra only to non-profit transplant centers and put it in the hands of the most qualified surgeons. But it can also ignore the traditional network of transplant centers and sell the island to private facilities. Witkowski is particularly concerned about this latter possibility. In private clinics where there is no requirement to disclose results, there may be “no responsibility…no later supervision.”

“They can choose to do it the right way, but they are not obligated to do it the right way.”

Ethical concerns

Authors of 2021 International transplantation The letter, a constellation of European endocrinologists, immunologists and transplant surgeons, condemned the ethical implications of approving Lantidra as a drug.

Granting private commercial companies with marketing rights for isolating similar islands could foreshadow the commercialization of human organs and their subparts.

Experts outlined other issues. He argued that Lantidra’s approval would likely block competition and limit treatment to the wealthiest people of his patients.

Witkowski shares the same concerns. According to him, the waiting list for organ transplants is United Network for Organ Sharing (unos), a nonprofit organization committed to equitable distribution of organs based on patient needs. But, as a private company, Celtran “can choose who they want to give it.” Island is eligible for insurance reimbursement, but the business may have a strong incentive to attach a high price to Lantidra and out of reach of some patients in need.

Celtran was granted seven years of exclusiveness under the Orphan Drug Act, but business Officially He has pledged to abandon exclusivity and allow other companies to submit BLAs and participate as an approved island supplier. However, Witkowski pointed out that Celltrans can easily revoke its exclusiveness.

“It’s very unfortunate.”

The approval of Lantidra as a drug appears to fly in the face of a tradition of non-profit cooperation that helped develop the island transplant in the first place.

When Ricordi invented his technique of islet cells, a technique that Celtran needed for Lantidra, he shared it freely. I was proud to develop it and share it all around the world. It aims to harden type 1 diabetes in the fastest and most efficient way possible, abandon royalties and create available equipment, drawings and training. ”

Ricordi explained that he was inspired by the scientists who discovered insulin, saying he wanted it to sound inevitable. Nobel Prize winner Frederick Bunting and his colleagues The insulin patents were sold for $1.00 each In the 1920s, life-saving medicines were distributed as quickly and affordably as possible.

Brutal irony is that Ricordi’s innovation is now essentially reserved in the United States for exclusive use of unrelated, commercial businesses.

“It’s a very sad to see it all swept into commercial entities because of this outdated FDA regulations, keeping it nonprofits, keeping it nonprofits, and seeing it all swept into commercial entities. I’m happy with the Seltran. I’m not criticizing them. They were played by the rules. … But I hope the FDA focuses on more serious issues.”

Witkowski is not sure what will happen next. He hopes Senator Lee and other lawmakers who have pledged to support the island’s law will not step back.

“But I don’t know what will happen. I don’t think they were expecting this response from the FDA. I’m waiting for them to let us know if they’re going to give up and if they’ll continue to fight.”

This law requires bipartisan cooperation to pass the law. It is lacking in our broken political environment.

Witkowski said, “If this island passes through its actions, it becomes a national resource, just like all other organs, and is protected by law.”