Erenumab Immunogenicity: a Pooled Analysis of Phase 2 and Phase 3 Migraine Prevention Clinical Trials (P4.098)

Objective: To determine the frequency of occurrence and potential clinical impact of anti-erenumab antibodies. Background: Anti-drug antibodies, commonly reported with biologics, may impact the efficacy, safety, and pharmacokinetics of the drug. Erenumab is a fully human anti-CGRP receptor antibody in development for migraine prevention. Here we report a pooled analysis of erenumab immunogenicity. Design/Methods: Data were obtained from all phase 2/phase 3 placebo-controlled clinical trials (NCT01952574, NCT02066415 [and open-label extension study, NCT02174861], NCT02456740, NCT02483585) that evaluated erenumab for migraine prevention. Serum was tested for anti-erenumab binding antibodies (BAbs); BAb-positive samples were tested for neutralizing antibodies (NAbs). Pooled data were used to determine the impact of anti-erenumab antibodies on efficacy, safety, and pharmacokinetics. Results: Subject incidence of BAbs during the double-blind phase of the four placebo-controlled trials was 6.3% (56/884) with 70 mg (of 3 NAb-positive subjects, 2 were NAb-negative by end of study [EOS]), and 2.6% (13/504) with 140 mg (0 NAb-positive). With continued treatment, more than 50% of BAb-positive subjects reverted to BAb-negative status by EOS. Mean (SE) change in monthly migraine days from baseline to month 3 with the 70-mg/140-mg dose was −3.2 (0.2)/−3.6 (0.2) in BAb-negative subjects and −3.2 (0.7)/−4.1 (0.8) in BAb-positive subjects. Mean change in monthly migraine days from baseline to month 6 with the 70-mg/140-mg dose was −3.5 (0.2)/−3.8 (0.2) in BAb-negative subjects and −3.2 (0.9)/−5.2 (0.9) in BAb-positive subjects. There was no impact of anti-erenumab antibodies on safety, in particular, injection-site reactions, hypersensitivity, and immune-related disorders. Despite an overall lower exposure (35–40%, week 12) at the group level, the concentrations of erenumab in individual BAb-positive subjects overlapped with those of BAb-negative subjects. Conclusions: Based on this pooled analysis, anti-erenumab antibodies have a low occurrence rate, high reversion rate, and most importantly, no appreciable clinical impact on the efficacy or safety in erenumab-treated subjects. Study Supported by: Amgen Inc. Disclosure: Dr. Vargas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen, Alder, Allergan, Avanir, Pernix, Teva, Lilly. Dr. Starling has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder, Amgen, Eli Lilly & Company, eNeura. Dr. Silberstein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Receives honoraria from Alder Biopharmaceuticals; Allergan, Inc.; Amgen; Avanir Pharmaceuticals, Inc.; eNeura; ElectroCore Medical, LLC; Labrys Biologics; Medscape, LLC; Medtronic, Inc.; Neuralieve; NINDS; Pfizer, Inc.; and Teva Pharmaceuticals. Dr. Silberstein has received research support from His employer receives research support from Allergan, Inc.; Amgen; Cumberland Pharmaceuticals, Inc.; ElectroCore Medical, Inc.; Labrys Biologics; Eli Lilly and Company; Merz Pharmaceuticals; and Troy Healthcare. Dr. Zhou has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen Inc. Dr. Trotman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen. Dr. Trotman holds stock and/or stock options in Amgen. Dr. Xue has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen. Dr. Xue has received compensation for serving on the Board of Directors of Amgen. Dr. Sahebkar-Moghaddam has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen. Dr. Picard has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen. Dr. Picard has received compensation for serving on the Board of Directors of Amgen. Dr. Mikol has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen. Dr. Mikol has received compensation for serving on the Board of Directors of Amgen.