Efficacy, Safety, and Tolerability of Efgartigimod in Patients with Chronic Inflammatory Demyelinating Polyneuropathy: Results from the ADHERE Trial
Jeffrey Allen1, Ivana Basta2, Christian Eggers3, Jeffrey Guptill4, Kelly Gwathmey5, Channa Hewamadduma6, Erik Hofman7, Yessar Hussain8, Satoshi Kuwabara9, Frank Leypoldt10, Jie Lin11, Marta Lipowska12, Murray Lowe7, Giuseppe Lauria Pinter13, Luis Querol14, Niraja Suresh15, Anissa Tse7, Peter Ulrichts7, Pieter Van Doorn16, Benjamin Van Hoorick7, Ryo Yamasaki17, Richard Lewis18
1Department of Neurology, University of Minnesota, 2Neurology Clinic, University Clinical Center of Serbia, University of Belgrade, 3Department of Neurology, Kepler University Hospital, 4Department of Neurology, Duke University, 5Neuromuscular Division, Virginia Commonwealth University, 6Academic Neurology Unit, Sheffield Teaching Hospitals NHS Foundation Trust, 7argenx, 8Austin Neuromuscular Center, 9Department of Neurology, Graduate School of Medicine, Chiba University, 10Department of Neurology, and Neuroimmunology, Institute of Clinical Chemistry, University Kiel, 11Department of Neurology, Huashan Hospital, Fudan University, 12Department of Neurology, Medical University of Warsaw, 13Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico Carlo Besta, 14Department of Neurology, Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, 15Department of Neurology, University of South Florida, 16Department of Neurology, Erasmus University Medical Center, 17Department of Neurology, Kyushu University Hospital, 18Department of Neurology, Cedars-Sinai Medical Center
Objective:

Assess the efficacy and safety of subcutaneous (SC) efgartigimod PH20 (co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP).

Background:

Despite available treatments, many patients with CIDP continue to have debilitating symptoms. Efgartigimod is a human IgG1 antibody Fc fragment that blocks the neonatal Fc receptor (FcRn), decreasing recycling of immunoglobulin G (IgG) and reducing pathogenic IgG autoantibody levels that may play a role in CIDP pathogenesis.

Design/Methods:

ADHERE (NCT04281472) was a two-part, multicenter, randomized, double-blinded, placebo-controlled trial that enrolled adult patients with CIDP (diagnosis confirmed by external committee) who were treatment-naive or receiving standard treatments, which were withdrawn in a ≤12-week run-in period. Patients with active disease entered a ≤12-week open-label phase of 1000 mg efgartigimod PH20 SC weekly (Stage A) and treatment responders entered a subsequent randomized-withdrawal phase up to 48-weeks of weekly treatment versus placebo (Stage B). Primary objectives were evidence of clinical improvement (Stage A) and efficacy of efgartigimod PH20 SC versus placebo based on time to occurrence of clinical deterioration measured using time to first adjusted INCAT score deterioration (Stage B).

Results:

322 entered Stage A, and of these, 221 were randomized and treated in Stage B (111 efgartigimod, 110 placebo). In Stage A, 214 (66.5%) participants were classified as treatment responders (95% CI: 61.0; 71.6). In Stage B, efgartigimod significantly reduced the risk of clinical deterioration (relapse) (HR: 0.394; 95% CI: 0.25; 0.61) versus placebo (p=0.000039). I-RODS and grip strength showed similar features as the INCAT score. Reduced risk of clinical deterioration was shown in patients receiving corticosteroids, intravenous or subcutaneous immunoglobulin, or no treatment prior to study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none being related to treatment.

Conclusions:

CIDP patients treated with efgartigimod PH20 maintained a clinical response to treatment and remained relapse-free longer than those treated with placebo.

10.1212/WNL.0000000000206324