ADHERE+ Trial Interim Analysis: Long-Term Safety and Efficacy of Efgartigimod in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Topic:

Clinical Trials

Poster Number: 341 T

Author(s):

Jeffrey A. Allen, MD, University of Minnesota, Minneapolis, MN, USA, Andrea Chamberlain, PharmD, argenx, Jie Lin, MD, Huashan Hospital, Fudan University, Shanghai, China, Mark Stettner, MD, PhD, University Medicine Essen, Essen, Germany, Jeffrey T. Guptill, MD, argenx, Ghent, Belgium, Geoffrey Istas, PhD, argenx, Ghent, Belgium, Arne De Roeck, PhD, argenx, Ghent, Belgium, Satoshi Kuwabara, MD, Chiba University, Chiba, Japan, Giuseppe Lauria Pinter, MD, IRCCS Foundation “Carlo Besta” Neurological Institute & University of Milan, Milan, Italy, Luis Querol, MD, PhD, Hospital de La Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain, Niraja Suresh, MD, Lakeland Regional Health, Lakeland, FL, USA, Chafic Karam, MD, 2University of Pennsylvania, Philadelphia, PA, USA, Thomas Skripuletz, MD, Hannover Medical School, Hanover, Germany, Simon Rinaldi, MBChB, PhD, University of Oxford, Oxford, UK, Andoni Echaniz-Laguna, MD, PhD, CERAMIC, Bicêtre University Hospital, Le Kremlin-Bicêtre, France, Channa Hewamadduma, MBChB, PhD, Sheffield Teaching Hospitals Foundation NHS Trust, Sheffield, UK, Benjamin Van Hoorick, MD, argenx, Ghent, Belgium, Ryo Yamasaki, MD, PhD, 8Kyushu University Hospital, Fukuoka, Japan, Pieter A. van Doorn, MD, PhD, Erasmus University Medical Center, Rotterdam, the Netherlands, Richard A. Lewis, MD, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Background/objectives: During ADHERE (NCT04281472), subcutaneous (SC) efgartigimod PH20 (neonatal Fc inhibitor co-formulated with recombinant human hyaluronidase PH20) reduced risk of relapse, improved functional assessments, and was well tolerated in participants with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). ADHERE+ (open-label extension, NCT04280718) assessed long-term safety, tolerability, and efficacy of efgartigimod PH20 SC in participants with CIDP. Methods: At study enrollment, participants were required to be off treatment or withdraw from standard treatments during the ≤12-week ADHERE run-in period. Participants could roll over to ADHERE+ to receive weekly efgartigimod PH20 SC 1000 mg if they completed or experienced clinical deterioration during the placebo controlled ADHERE stage B (placebo or efgartigimod PH20 SC 1000 mg). Endpoints included incidence of adverse events (AEs) and changes from ADHERE run-in (study enrollment) baseline over time in functional assessments until ADHERE+ Week 36 (interim analysis, data cutoff: February 16, 2024). Results: At data cutoff, 99% (228/229) of participants had entered ADHERE+ and received ≥1 dose of efgartigimod PH20 SC. Mean (SD) treatment duration was 58.0 (33.8) weeks (263 patient-years of observation). Efgartigimod PH20 SC was well tolerated in ADHERE/ADHERE+. In total, 75.0% of participants had ≥1 AEs; most common: COVID-19 (16.2%) and upper respiratory tract infection (10.5%), which were mild to moderate in severity. In total, 30.7% had treatment-related AEs, 7.9% had AEs leading to treatment discontinuation, and 45.6% had AEs of special interest (infections/infestations). Two deaths (CIDP worsening, cardiac arrest) occurred, neither considered efgartigimod related. In post hoc analyses, mean (standard error) change from run-in baseline in adjusted Inflammatory Neuropathy Cause and Treatment (n=150), Inflammatory Rasch-built Overall Disability Scale (centile metric; n=150), and (dominant hand) grip strength scores (n=149) were −1.2 (0.15) and 8.8 (1.46) points and 17.5 (2.02) kPa, respectively, at ADHERE+ Week 36 (N=150), each representing clinically meaningful improvements. Conclusions: Interim results from ADHERE+ indicate long-term safety and effectiveness of efgartigimod PH20 SC in participants with CIDP.