Imlifidase therapy: exploring its clinical uses

ABSTRACT

Introduction

Imlifidase, the IgG-degrading enzyme derived from Streptococcus pyogenes, can cleave all four human IgG subclasses with precise specificity. All IgG molecules can be inactivated for ~1-to-2 weeks, until new IgG synthesis is detected.

Areas covered

Imlifidase was first studied for the desensitization of highly HLA-sensitized patients to enable kidney transplantation. It is currently being evaluated for kidney transplant recipients who have antibody-mediated rejection (AMR), those with acute kidney injury in the setting of anti-glomerular basement membrane disease, and those with Guillain–Barré syndrome. In 2020, imlifidase received conditional approval from the European Medicines Agency for use to desensitize deceased-donor kidney transplant recipients with a positive crossmatch. Literature search through PubMed revealed that so far, 39 crossmatched-positive patients, i.e. in the presence of donor-specific alloantibodies (DSA) on the transplantation day, have received imlifidase prior to kidney transplantation in four single-arm, open-label, phase II studies. Results at 3-year follow-up are good, i.e. allograft survival is 84%, despite 38% of patients presenting with acute AMR. Mean estimated glomerular filtration rate at 3 years was 55 mL/min/1.73 m².

Expert opinion

The major hurdle now is how to prevent/avoid DSA rebound within days 5–15 post-transplantation. Thus, imlifidase represents a major breakthrough for highly HLA-sensitized kidney transplant candidates, particularly those that have calculated panel-reactive alloantibodies of ≥90%.

KEYWORDS:

• Antibody-mediated rejection
• anti-GBM disease
• desensitization
• donor-specific alloantibody
• IgG
• imlifidase
• IdeS
• kidney transplantation
• positive crossmatch
• Streptococcus pyogenes

Article highlights

• Imlifidase, the IgG-degrading enzyme derived from Streptococcus pyogenes, has the capacity to cleave all four human subclasses of IgG with precise specificity.

• Imlifidase enables transplantation in highly sensitized HLA kidney transplant candidates with a positive crossmatch. The 3-year post-treatment results are good in terms of renal function, even though 38% of patients had an acute antibody-mediated rejection.

• In August 2020, imlifidase received conditional approval from the European Medicines Agency to be used to desensitize deceased-donor kidney transplant recipients with a positive crossmatch.

• After 6 months of imlifidase therapy, 67% (10/15) of patients that had circulating anti-glomerular basement membrane autoantibodies and acute kidney injury were dialysis independent compared to 18% (9/50) of patients in a historical control cohort.

• Imlifidase is currently being evaluated for kidney transplant recipients who present with antibody-mediated rejection and for those with Guillain–Barré syndrome.

Declaration of interest

L Rostaing has received honoraria from Hansa for advisory board and consultancy roles. J Noble has received honoraria from Hansa for speaker roles. P Malvezzi has received honoraria from Hansa for advisory board and consultancy roles. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.