PHARMACODYNAMIC NONINFERIORITY STUDY COMPARING SUBCUTANEOUS EFGARTIGIMOD PH20 WITH INTRAVENOUS EFGARTIGIMOD: RESULTS OF PHASE 3 ADAPT-SC STUDY

Topic:

Clinical Trials

Poster Number: 131

Author(s):

Matthew Behr, argenx, George Li, Medsol Clinical Research Center Inc, Port Charlotte, FL, Tuan Vu, MD, University of South Florida, Vera Bril, MD, Ellen & Martin Prosserman Centre for Neuromuscular Diseases, University Health Network, Temur Margania, MD, Department of Neurology and Neurorehabilitation, New Hospitals, Tbilisi, Georgia, Denis Korobko, State Budgetary Healthcare Institution of Novosibirsk Region, Novosibirsk, Russia, Marek Smilowski, Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Li Liu, argenx, Sophie Steeland, argenx, Jan Noukens, Curare Consulting BV, Benjamin Van Hoorick, argenx, Jana Podhorna, argenx, Yuebing Li, MD, PhD, Neuromuscular Center, Cleveland Clinic, Cleveland, OH, Kimiaki Utsugisawa, MD, PhD, Hanamaki General Hospital, Heinz Wiendl, Department of Neurology, University of Münster, Münster, Germany, Jan De Bleecker, MD, PhD, Ghent University Hospital, Renato Mantegazza, MD, Fondazione IRCCS Istituto Neurologico Carlo Besta, James Howard, MD, FAAN, The University of North Carolina at Chapel Hill

Background:
Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total IgG levels, including pathogenic IgG autoantibody levels, by neonatal Fc receptor blockade. Efgartigimod was well tolerated and efficacious when administered intravenously (IV) in the phase 3 ADAPT study in patients with generalized myasthenia gravis (gMG). ADAPT-SC is a phase 3, pharmacodynamic (PD) noninferiority study comparing subcutaneous (SC) efgartigimod PH20 injections (coformulated with recombinant human hyaluronidase PH20) with efgartigimod IV infusions in gMG patients.
Objectives:
To demonstrate that efgartigimod PH20 SC is noninferior to efgartigimod IV based on total IgG reductions at day 29.
Methods:
110 adults with gMG were randomized 1:1 and treated with 4 weekly injections of efgartigimod PH20 SC 1000 mg or 4 weekly infusions of efgartigimod IV 10 mg/kg. Primary endpoint was percent reduction from baseline in total IgG levels at day 29, using a noninferiority margin of 10%. Secondary endpoints included clinical efficacy, assessed utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, and safety.
Results:
Efgartigimod PH20 SC demonstrated PD noninferiority to efgartigimod IV, with observed mean[SE] reductions in total IgG levels from baseline at day 29 (SC:–64.7%[1.95]; IV:–62.3%[1.24]). Similar clinical efficacy was observed in each group with improvements from baseline MG-ADL total score at week 4 (mean[SE] improvement, SC:–5.1[0.38]; IV:–4.7[0.37]). Both formulations were well-tolerated, consistent with previous IV studies. Most frequent adverse effects were headache (12.7% SC and IV), injection site rash (14.5% SC; 0% IV), and injection site erythema (12.7% SC; 0% IV). Injection site reactions were predominately mild-moderate and did not result in discontinuation.
Conclusion:
ADAPT-SC met its primary endpoint of total IgG reduction from baseline at day 29 demonstrating noninferiority of efgartigimod SC to efgartigimod IV. Both formulations were well tolerated and demonstrated similar efficacy. The SC formulation of efgartigimod provides potential for an additional route of administration for gMG patients.