Imlifidase Opens a Transplant Window, With Oriol Bestard, MD, PhD

Imlifidase (Idefirix) enabled deceased-donor kidney transplantation in highly sensitized patients with a positive crossmatch. Graft failure-free survival was 90% at 1 year in the European post-authorization efficacy and safety (PAES) trial.¹

Oriol Bestard, MD, PhD, head of the Department of Nephrology and Kidney Transplantation at Vall d’Hebron University Hospital in Barcelona, Spain, presented the data at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado. In an interview with HCPLive, Bestard said the open-label, nonrandomized trial confirms earlier phase 2 findings. He added that it leaves open questions about antibody rebound and concomitant immunosuppression.

Highly Sensitized Patients Face Limited Access to Kidney Transplant

Highly sensitized patients carry preformed antibodies against human leukocyte antigens (HLA), which can damage a transplanted organ. These patients make up about 10%–15% of people on transplant waiting lists in the US and Europe. They tend to wait longer for a compatible organ and face a greater risk of dying while waiting.²

“The trial is focusing on a really unmet medical need, which is a subset of patients that are waiting for transplantation, which are called highly sensitized,” Bestard said. “They have developed HLA antibodies in the past for different factors, and they are not capable of being transplanted.”

Imlifidase is an IgG-cleaving enzyme derived from Streptococcus pyogenes. It inactivates all IgG subclasses, including HLA antibodies, within hours of administration.² Bestard explained that the enzyme also depletes IgG on the surface of B cells. Antibodies typically return within about 7 to 8 days.

“It gives a sort of window of opportunity for these patients to be transplanted during that period of time without having donor-specific antibodies,” he said.

Imlifidase received conditional marketing authorization in the European Union in August 2020, contingent on a confirmatory post-authorization study.² In the US, the US Food and Drug Administration (FDA) accepted a biologics license application for imlifidase in February 2026. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of December 19, 2026.²

PAES Trial Design in Crossmatch-Positive Deceased-Donor Transplants

PAES (NCT05369975) was a controlled, nonrandomized, open-label trial requested by the European Medicines Agency (EMA) to support full marketing authorization.¹ The trial ran at 22 transplant centers across 11 countries in the European Union and the United Kingdom.³

Investigators treated 50 highly sensitized patients who received crossmatch-positive deceased-donor kidney offers. All were considered unlikely to be transplanted under available allocation systems, including prioritization programs for highly sensitized patients. Imlifidase was given to convert the positive crossmatch to negative before transplantation.¹

Bestard noted that patients first underwent delisting of selected HLA antibodies according to each transplant program’s local policies. He added that the trial included 2 control groups. One was transplanted concurrently, and the other was a retrospective sensitized group drawn from a large European registry. Neither group had a positive crossmatch.

The primary outcome was graft failure-free survival at 1 year. Secondary outcomes at 1 year included:¹

• Kidney function assessed by estimated glomerular filtration rate (eGFR)
• Patient survival
• Graft survival
• Delayed graft function
• Antibody-mediated rejection (AMR)
• Safety

Imlifidase Results: Graft Survival, eGFR, and AMR at 12 Months

Graft failure-free survival was 90% at 1 year in patients desensitized with imlifidase (n = 50). Graft survival was 92% and patient survival was 98%. Mean eGFR, calculated by the Modification of Diet in Renal Disease (MDRD) equation, was 51.04 mL/min/1.73 m² (n = 45).¹

Delayed graft function occurred in 40% of patients, with a median duration of 14 days. AMR occurred in 56% of recipients, but no allograft loss was associated with AMR.¹ Bestard said the AMR episodes were managed according to each center’s protocol and did not affect 12-month outcomes.

Investigators reported no new safety signals, and no imlifidase infusions were stopped because of infusion reactions. They concluded that imlifidase enables transplantation with successful kidney function at 1 year, with a safety profile consistent with prior experience.¹

Antibody Rebound and Immunosuppression Remain Open Questions

Bestard said the findings may give patients who have waited for long periods, or indefinitely, a path to transplant. He said key questions remain about which patients rebound and how to pair imlifidase with other therapies.

“We really need to understand much more about the biology now of how and why some of these patients do show this very severe rebound of antibodies after imlifidase, why some others do not, and what type of immunosuppressive therapies should we concomitantly use together with imlifidase,” Bestard said.

Editors’ Note: Disclosures for Bestard include Hansa Biopharma.

References

1. Bestard O, et al. Post-Authorization Efficacy and Safety (PAES): An Open-Label Post-Authorization Trial of 50 Imlifidase Crossmatch-Positive Deceased-Donor Kidney Transplants in Europe. Abstract FR-OR103 presented at: American Society of Nephrology Kidney Week 2026; October 22–25, 2026; Denver, CO.

2. Hansa Biopharma announces positive Idefirix PAES results presented in the High-Impact Clinical Trials session at ASN Kidney Week. News release. Hansa Biopharma. Published October 23, 2026. Accessed October 28, 2026.

3. Hansa Biopharma reports positive efficacy and safety results from Idefirix European post authorization study in kidney transplantation. News release. Hansa Biopharma. Published May 27, 2026. Accessed October 28, 2026.