Hansa Biopharma has announced the completion of enrollment in its 20-HMedIdeS-19 Post Authorization Efficacy and Safety (PAES) study, a Phase 3 confirmatory trial investigating imlifidase in highly sensitized kidney transplant patients across Europe.
The open-label study is evaluating one-year patient and graft survival in highly sensitized patients who have undergone HLA-incompatible kidney transplantation following desensitization treatment with imlifidase. The company anticipates data readout in the second half of 2026, after which it plans to submit findings to the European Medicines Agency to seek full authorization.
"The PAES study is an important part of Hansa's continued commitment to ensuring access to potentially lifesaving IDEFIRIX therapy for highly sensitized kidney transplant patients," said Søren Tulstrup, President and CEO of Hansa Biopharma. "Those considered highly sensitized and waiting for a transplant continue to face very long wait times due to their immunological status which poses a significant barrier to finding a compatible organ."
Study Design and Patient Population
The PAES study enrolled 50 highly sensitized adult kidney transplant patients who received desensitization treatment with imlifidase. Additionally, 64 patients who underwent kidney transplantation without desensitization were included in a concurrent reference cohort to account for center-to-center variability in post-transplant management. The trial is being conducted across 22 sites throughout Europe.
Thomas Lorant, transplant surgeon at Uppsala University and the coordinating investigator for the trial, highlighted the transformative potential of imlifidase: "Creating an IgG-free window by inactivating the donor-specific antibodies, it makes desensitization-enabled HLA-incompatible kidney transplantation a viable option for those considered highly sensitized and who were previously left on transplant waiting list for extended, often indefinite time."
The Challenge of Highly Sensitized Patients
Highly sensitized patients have pre-formed donor-specific antibodies (DSAs) with broad reactivity against human leukocyte antigens (HLAs). These antibodies can cause tissue damage and potentially lead to transplant rejection, making it extremely difficult to find compatible donor organs.
Due to their complex immunological profiles, highly sensitized patients typically spend longer than average on transplant waiting lists, with evidence showing that this extended waiting time correlates with increased mortality risk. Across the U.S. and Europe, these patients comprise approximately 10-15% of all patients on kidney transplant waiting lists.
How Imlifidase Works
Imlifidase is an antibody-cleaving enzyme derived from Streptococcus pyogenes that specifically targets and cleaves immunoglobulin G (IgG) antibodies, inhibiting IgG-mediated immune responses. The treatment has a rapid onset of action, cleaving IgG antibodies and inhibiting their activity within hours after administration.
For highly sensitized transplant patients, imlifidase creates a window of opportunity for transplantation by temporarily removing the barrier of donor-specific antibodies. By the time the body begins to synthesize new IgG antibodies, the patient is already receiving post-transplant immunosuppressive therapy to reduce the risk of organ rejection.
Regulatory Status and Future Applications
Imlifidase, marketed as IDEFIRIX®, received conditional marketing authorization in Europe in 2020 for the desensitization treatment of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor. The current PAES study is an obligation following this conditional approval.
The therapy was reviewed as part of the European Medicines Agency's PRIority Medicines (PRIME) program, which supports medicines that may offer significant advantages over existing treatments or benefit patients without treatment options.
Beyond kidney transplantation, Hansa Biopharma is also evaluating imlifidase in late-stage trials for autoimmune diseases where IgG antibodies drive disease progression, as well as a pre-treatment for gene therapy in patients with anti-AAV antibodies.
Addressing a Significant Unmet Need
Kidney disease can progress to kidney failure or End-Stage Renal Disease (ESRD), which affects nearly 2.5 million patients worldwide. For suitable patients with ESRD, kidney transplantation offers improved survival and quality of life benefits compared to long-term dialysis.
Currently, approximately 170,000 kidney patients in the U.S. and Europe are waiting for a new kidney. For the subset of highly sensitized patients, innovative approaches like imlifidase may represent a crucial advancement in increasing access to life-saving transplantation.
The completion of enrollment in this Phase 3 study marks a significant milestone in Hansa Biopharma's efforts to generate the evidence needed for full authorization of imlifidase in Europe, potentially expanding access to this innovative therapy for patients with limited transplant options.
