A group of more than 50 experts in the field of pancreatic islet cell transplantation is calling for reclassification of the type 1 diabetes therapy from biologic drug to human organ.
On April 15 an advisory panel to the US Food and Drug Administration (FDA) voted to endorse approval of a biologic license application (BLA) for the allogeneic human islet product donislecel (Lantidra) developed by CellTrans.
The treatment would be intended for people with type 1 diabetes complicated by hypoglycemic unawareness or other issues that result in extreme glycemic lability despite optimized insulin therapy.
During the public comment period of the day-long meeting, Piotr Witkowski, MD, PhD, director of the Pancreatic Islet Cell Transplant Program at the University of Chicago, Illinois, spoke against FDA approval on behalf of the Islets for US Collaborative. Comprised of over 50 experts in the field, the organization aims to “protect [islets] from commercialization and preserve the human pancreas and islets as public resources for the public good.”
Witkowski argued that rather than the FDA granting the company an exclusive BLA, human islets should be regulated as transplanted organs under the auspices of the Health Resources and Services Administration (HRSA) with oversight by the Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS).
FDA Stance Means Islet Transplants in US Fall Behind Other Nations
Human pancreatic islet cells are isolated from deceased donor pancreases and transplanted into the recipient’s liver. They require the same immunosuppressive regimens as do all organ transplants.
“Islets are human micro-organs and should be regulated as pancreas and other human organs…Islets are not drugs and they are not cellular therapy,” Witkowski emphasized.
Many parts of the world, including countries in Europe, Canada, Australia, and Japan, regulate islets as organs rather than drugs, he noted. “FDA’s position that allogeneic islets are drugs and require a BLA has prevented islet transplantation from becoming a standard of care procedure in the US, in contrast to many other countries,” he noted.
Witkowski argued that many US academic transplant centers have successfully processed human islets for transplantation in clinical trials without a BLA over the past 20 years, but unlike a manufacturer, those institutions are not in a position to obtain such a license.
Granting 7 years of marketing exclusivity, he said, would give the manufacturer leverage over availability, cost, and safety monitoring of patients post-transplant.
Under HRSA rules the OPTN/UNOS oversees organ transplant programs and monitors patient outcomes following transplantation, but such monitoring isn’t mandated for drugs. This raises a safety concern, he asserted.
FDA, CellTrans See it Differently
There were no responses to public commentary remarks during the meeting per protocol, so Medscape Medical News reached out to the FDA, CellTrans, and the US Department of Health and Human Services (HHS). (Both FDA and HRSA are agencies within HHS, and the OPTN is operated by UNOS under contract with HHS.)
An FDA spokesperson replied by email: “The manufacture and transfer of allogeneic pancreatic islet cells is not analogous to whole organ pancreas transplantation, and we do not agree with the suggestion that pancreatic islets meet the definition of a vascularized human organ.”
The spokesperson also noted: “FDA established the regulatory requirements for allogeneic islets based on the specific characteristics of that product, its manufacture and intended use, and did so in a transparent manner with input from relevant stakeholders. There is no plan to revise or reconsider this regulatory approach.”
And CellTrans said: “CellTrans submitted a BLA following federal regulations governing cell therapies. The code of federal regulations on biologics aims at ensuring safe, high quality therapies. CellTrans’s commitment to safety is evidenced in the filings it has made to the FDA, and it will continue to comply with all governmental mandates to maintain safety.”
The company also said in its email that it “aims to offer islet cell transplantation to patients in need as a standard care option. As part of its commitment to facilitate such access, CellTrans has waived all exclusivity rights available to it as part of its application.”
Moreover, “CellTrans is a manufacturer of islets and is not involved in patient care or organ allocation. CellTrans simply processes organs accepted by the transplant center via the UNOS allocation system and provides the islet cell preparation to the hospital transplant center.”
The HHS press office did not respond by deadline nor after subsequent repeated requests.
Based on the discussion at the advisory panel meeting, it’s unclear how many patients this issue will affect.
Panel members weighed the risks of immunosuppression against the benefit of transplanted islets, given that in recent years advances in diabetes technology and treatment have reduced the number of patients with hypoglycemic unawareness and extreme glycemic lability.
The FDA is expected to announce a decision on donislecel licensure in August 2021.
Witkowski has reported no relevant financial relationships.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.