Abstract: SA-OR83
Superiority of Imlifidase over Plasma Exchange in Rapid and Efficient Elimination of All IgGs, Including Donor Specific Antibodies (DSAs) Assessed in an Antibody-Mediated Rejection (AMR) Trial
Session Information
- Transplantation: Clinical Management and Monitoring
October 26, 2024 | Location: Room 25, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Jordan, Stanley C., Cedars-Sinai Medical Center, Los Angeles, California, United States
- Bohmig, Georg, Medizinische Universitat Wien Universitatsklinik fur Innere Medizin III, Wien, Wien, Austria
- Couzi, Lionel, Centre Hospitalier Universitaire de Bordeaux Service d'endocrinologie diabetologie et nutrition, Bordeaux, Nouvelle-Aquitaine, France
- Lefaucheur, Carmen, Hopital Saint-Louis, Paris, Île-de-France, France
- Montgomery, Robert Avery, NYU Langone Health, New York, New York, United States
- Rostaing, Lionel, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
- Legendre, Christophe M., Hopital Necker-Enfants Malades Service de Genetique Clinique, Paris, Île-de-France, France
- Hughes, Peter D., The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Chandraker, Anil K., Brigham and Women's Hospital, Boston, Massachusetts, United States
- Einecke, Gunilla, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
- Wyburn, Kate, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Runström, Anna, Hansa Biopharma AB, Lund, Sweden
- Tollemar, Jan G., Hansa Biopharma AB, Lund, Sweden
- Lefèvre, Paola A., Hansa Biopharma AB, Lund, Sweden
- Halleck, Fabian, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background
Antibody depletion using (PLEX) is regarded as SOC in the treatment of AMR. However, PLEX has inconsistencies in removal of pathogenic IgG (i.e., DSAs) due to multiple factors including re-equilibration from IgG distributed in extravascular spaces. Imlifidase, a protease that specifically inactivates all human subclasses of soluble and membrane bound IgG. Imlifidase is currently utilized for desensitization prior to kidney transplantation with inactivation of DSAs both in the intra- and extravascular space. In this AMR trial (NCT03897205), the primary endpoint was to compare removal of IgG DSAs with imlifidase to 5-10 PLEX sessions.
Methods
The comparison occurred in a phase 2 randomized, open-label, multi-center, multi-national trial with a 6-month follow-up conducted at 14 transplant centers. The trial included 30 patients with active or chronic active AMR after kidney transplantation. The primary endpoint analyzed the maximum reduction of all DSA levels for 5 d following the start of either treatment. The purpose of this presentation is the efficacy of removing IgG between the two treatment modalities.
Results
The median reduction of DSA was 97% for imlifidase compared to 42% for PLEX on day 5. The time to median maximum DSA depletion was 15h after imlifidase compared to day 9 for a median of 6 PLEX sessions. No complement-binding DSA was detectable 24h after treatment in any imlifidase patients, whereas no reduction was seen in PLEX treated patients. After the initial elimination of DSA, a rebound occurred to approximately 70% of baseline values for both groups. On average 3% of the pre-treatment IgG level remained after imlifidase, compared to 50% after PLEX at any timepoint. No meaningful safety issues were observed in the trial.
Conclusion
In a head-to-head comparison in kidney transplant recipients with AMR, one dose of imlifidase given over a 15-min infusion was more efficacious in reducing all IgG, both in speed and magnitude, compared to several PLEX sessions. Thus, imlifidase offers a rapid and effective option of hindering any IgG-mediated attack momentarily with a beneficial safety profile.
Funding
- Commercial Support – Hansa Biopharma AB