A review of imlifidase in solid organ transplantation

ABSTRACT

Introduction: Sensitization to human leukocyte antigens has long posed an obstacle to organ transplantation. With desensitization protocol refinement, new drug development, and organ allocation policy changes, access to transplant for sensitized patients has never been greater. Yet in spite of these advances the problem of donor-specific antibody remains incompletely solved, and many patients remain poorly served by the therapies that do exist.

Area covered: Imlifidase is a new drug with a mechanism of action that enables it to transiently yet efficiently eliminate donor-specific antibody over a much more rapid time course than any heretofore existing therapy. This unique property suggests that imlifidase may have far-reaching potential for patients in whom donor-specific antibodies may preclude successful transplantation. Below follows a review of the clinical experience with imlifidase to date as well as a discussion of the transplant applications that eagerly await the availability of this novel agent.

Expert opinion: Imlifidase is a first-in-class pharmaceutical agent that safely and efficiently cleaves IgG, and holds promise to be a game-changer for sensitized patients in need of lifesaving organ transplants.

KEYWORDS:

• Antibody-mediated rejection
• desensitization
• hla sensitization
• incompatible transplantation
• kidney transplantation

Article highlights

• Sensitization to HLA continues to present a formidable barrier to solid organ transplantation, and while strategies at desensitization have evolved and improved, the current treatments remain inefficient, costly, and are not universally successful.

• Imlifidase, an endopeptidase, a first-in-class agent that rapidly and efficiently cleaves human IgG. When administered to sensitized patients, imlifidase eliminates virtually all circulating HLA antibody in approximately 4-6 hours.

• In three clinical trials, sensitized patients including those with high strength positive crossmatches have been desensitized with imlifidase, and have undergone subsequent kidney transplantation.

• The effect of imlifidase is transient, and IgG begins to reconstitute at approximately 7 days post-dosing. There is benefit to this repopulation in that protective memory immune responses are preserved. However, there is also risk in transplant recipients where donor-specific HLA antibody rebound can trigger antibody-mediated rejection. While the cases of rejection observed in the studies to date were successfully treated with standard therapies, further refinement of the use of imlifidase will be needed to minimize the rejection risk post-transplantation.

• When living donation is not an option, no existing desensitization therapy has the capacity to remove HLA antibody on a timecourse compatible with transplanting across a starting positive crossmatch. Imlifidase is a first-in-class drug that offers this capability. For the most highly sensitized patients, the alternative of waiting for a compatible organ all too often results in death on the waiting list.

• This emerging agent holds promise to increase transplant opportunities for sensitized patients in need of any lifesaving solid organ.

This box summarizes key points contained in the article.

Declaration of interest

The author has received consulting fees from Hansa Biopharma for work unrelated to the trials described here. The author has 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 relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.