Magnitude of Response with Subcutaneous Efgartigimod PH20 in Chronic Inflammatory Demyelinating Polyneuropathy: ADHERE/ADHERE+ Trials

Topic:

Clinical Trials

Poster Number: P379

Author(s):

Jeffrey A. Allen, Department of Neurology, University of Minnesota, Minneapolis, MN, USA, Richard A. Lewis, MD, Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA, Luis Querol, Hospital de La Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain, Christian Eggers, Department of Neurology, Kepler University Hospital, Johannes Kepler University, Linz, Austria, Satoshi Kuwabara, Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan, Yessar M. Hussain, Austin Neuromuscular Center, Austin, TX, USA, Kelly G. Gwathmey, MD, Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA, Jeffrey T. Guptill, argenx, Ghent, Belgium, Geoffrey Istas, argenx, Ghent, Belgium, Benjamin Van Hoorick, MD, argenx, Ghent, Belgium, Arne De Roeck, argenx, Ghent, Belgium, Ivana Basta, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, Pieter A. van Doorn, Department of Neurology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Background. Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. The multi-stage, double-blind, placebo-controlled, randomized-withdrawal ADHERE and ongoing, open-label extension ADHERE+ trials assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP).
Objectives. Participants with active CIDP (off-treatment or standard treatments withdrawn during run-in) received weekly efgartigimod PH20 SC 1000 mg (stage A). Responders were randomized to weekly efgartigimod PH20 SC 1000 mg or placebo (stage B). Participants with clinical deterioration in stage B or who completed ADHERE could enter ADHERE+ (weekly efgartigimod PH20 SC 1000 mg). Endpoints included changes in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) and Inflammatory Rasch-built Overall Disability Scale (I-RODS) (centile metric) scores, and safety.
Results. Improvement in mean aINCAT scores from run-in baseline to stage B baseline in participants receiving efgartigimod in ADHERE (n=97) was maintained up to Week 24 of ADHERE+ (n=86). Mean aINCAT scores deteriorated in participants receiving placebo in stage B (n=94) in ADHERE; this deterioration was reversed when they received efgartigimod in ADHERE+. A total of 60.8% (n=59), 34.0% (n=33), 22.7% (n=22), and 11.3% (n=11) of participants experienced improvements of ≥1, ≥2, ≥3, and ≥4 points in aINCAT scores from run-in baseline to stage B best improvement, respectively. Likewise, a total of 48.5% (n=47), 35.1% (n=34), 30.9% (n=30), and 24.7% (n=24) of participants experienced improvements of ≥4, ≥8, ≥12, and ≥16 points in I-RODS centile score from run-in baseline to stage B best improvement, respectively. Efgartigimod across ADHERE/ADHERE+ was generally well-tolerated; treatment-emergent adverse events were mild/moderate in severity.
Conclusions. Clinically meaningful improvements were reported for participants receiving efgartigimod PH20 SC 1000 mg during ADHERE based on functional (aINCAT) and daily activity (I-RODS) assessments. Improvements in aINCAT from run-in baseline through ADHERE with efgartigimod were maintained through Week 24 of ADHERE+. The safety profile of efgartigimod PH20 SC was similar between ADHERE/ADHERE+ and consistent with the previously demonstrated safety profile