FDA approves novel pancreatic islet cell therapy for adults with type 1 diabetes
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Key takeaways:
- The FDA approved the first allogenic pancreatic islet cellular therapy for adults with type 1 diabetes.
- In two trials, 21 of 30 adults receiving the therapy achieved insulin independence for at least 1 year.
The FDA approved an allogenic pancreatic islet cellular therapy for adults with type 1 diabetes who struggled to achieve their target HbA1c due to repeated episodes of severe hypoglycemia, according to an agency press release.
The novel cell therapy (Lantidra, CellTrans Inc.) is made from deceased donor pancreatic cells and is administered as a single infusion into the patient’s hepatic portal vein. According to the press release, the therapy’s mechanism of action is believed to be secretion of insulin by the infused islet beta cells, which may produce enough insulin in patients to allow them to no longer require insulin therapy. Additional infusions of islet cells may be required depending on response to the initial dose.
“Severe hypoglycemia is a dangerous condition that can lead to injuries resulting from loss of consciousness or seizures,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release. “Today’s approval, the first-ever cell therapy to treat patients with type 1 diabetes, provides individuals living with type 1 diabetes and recurrent severe hypoglycemia an additional treatment option to help achieve target blood glucose levels.”
In two single-arm trials, 30 adults with type 1 diabetes and hypoglycemia unawareness received between one and three infusions of the cell therapy. Of the cohort, 21 participants did not require insulin for at least 1 year, 11 participants did not need insulin for between 1 and 5 years and 10 participants achieved insulin independence for more than 5 years.
Adverse events varied depending on the number of infusions received and the length of follow-up. The most common adverse events were nausea, fatigue, anemia, diarrhea and abdominal pain, according to the release. Most of the trial participants had at least one serious adverse event related to the infusion procedure and the use of immunosuppressive medications needed to maintain islet cell viability. Some serious adverse events required the discontinuation of immunosuppressive medication, resulting in the loss of islet cell function and insulin independence. The FDA approved the therapy with patient-directed labeling to inform adults with type 1 diabetes about the benefits and risks of the therapy.
Perspective
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On June 28, the FDA approved the first cellular therapy for the treatment of type 1 diabetes. The product, donislecel (Lantidra; CellTrans Inc.) consists of purified human pancreatic islets isolated from a deceased donor pancreas. While isolated islets for transplantation have been available in clinical practice throughout much of Canada, Europe and Australia where national health services provide and regulate deceased donor islets similarly as whole organs used for transplantation, the U.S. regulation of deceased donor islets as a drug rather than an organ has imposed FDA requirements for biologic licensure that have precluded approval until now. The company that achieved this approval, CellTrans, is a faculty start-up founded by Dr. José Oberholzer when he was at the University of Illinois Chicago to commercialize the cell isolation facility at the University of Illinois Hospital for the purpose of obtaining biologic licensure for islet transplantation from the FDA.
Remarkably, the University of Illinois Chicago operating through CellTrans is the only one of eight U.S. academic islet manufacturing and clinical centers that contributed to the NIH-sponsored Clinical Islet Transplantation Consortium phase 3 trials of islet alone and islet-after-kidney transplantation to obtain a license approval. This is a tremendous milestone; however, challenges and limitations to the implementation of donislecel therapy remain. It is unclear how a single manufacturing site in Chicago will manage to provide deceased donor islets for transplantation to all appropriate candidates throughout the U.S. with type 1 diabetes experiencing recurrent episodes of severe hypoglycemia. Curiously, the license to CellTrans was granted based on 30 patients treated at the University of Illinois Chicago outside of the Clinical Islet Transplantation Consortium phase 3 trials. While the outcomes and adverse events experienced are similar to those reported by the Clinical Islet Transplantation Consortium, clinicians and patients are left wondering how the benefits and risks compare to those of the 72 patients treated as part of the multi-center Clinical Islet Transplantation Consortium phase 3 trials whose long-term follow-up was recently reported (Rickels MR, et al. Diabetes Care. 2022;doi:10.2337/dc21-2688). Importantly, because none of the CellTrans patients had a kidney transplant, the current labeling indication excludes such patents who make the most sense to receive islet transplantation as they already require immunosuppression to support their kidney graft.
In conclusion, the achievement of biologic licensure by CellTrans for the isolation of deceased donor islets for transplantation in patients with type 1 diabetes represents the first approval by the FDA of a cellular therapy for the treatment of diabetes and can have a tremendous impact on the lives of individuals burdened by the disease and its complication of hypoglycemia. This less invasive alternative to whole pancreas transplantation should really be available to any patient with type 1 diabetes considering a pancreas alone or pancreas-after-kidney transplant. Ensuring access of this important disease-modifying therapy to those who may benefit most, including for kidney transplant recipients, should be an important policy priority for both the FDA and the United Network for Organ Sharing that governs the allocation of pancreases procured from deceased donors for use in transplantation.
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