Analysis of Blood Pressure Following Short-Term and Long-Term Treatment with Erenumab (P4.103)

Objective: Assessment of blood pressure (BP)findings from the erenumab clinical development program. Background: Erenumab is a fully human monoclonal antibody which selectively inhibits the calcitonin gene-related peptide(CGRP) receptor, and is under investigation for migraineprevention. CGRP ligand is a vasodilator and its inhibition might theoretically increase BP. Addressing this theoretical risk through ancillary safety studies has been an important focus during the clinical development of erenumab. Design/Methods: Systolic and diastolic BP (SBP and DBP) were obtained at baseline and every 4 weeks in four placebo-controlled trials (NCT01952574, NCT02066415/NCT02174861, NCT02456740, NCT02483585). BP was recorded as the average of ≥2 measurements taken ≥5 minutes apart with subjects lying supine and rested for ≥5 minutes. In categorical analyses, a notable increase in BP was defined as an increase from baseline of ≥10 mmHg in DBP and/or ≥20 mmHg in SBP. Pooled placebo-controlled data from baseline and treatment Weeks 4, 8, and 12 were presented. In a separate Phase 1 study(NCT01723514), 24-hour continuous BP was assessed in healthy volunteers receiving erenumab monthly over 12 weeks. Results: BP was similar across treatment groups at baseline, and remained stable over 12 weeks, with no difference observed between erenumab and placebo. At Week 12, mean (SD) changein SBP was −0.4 (9.6), −0.5 (10.0), and −1.0(9.8) mmHg, and in DBP was −0.6 (7.1), −0.3 (7.7), and −0.4 (7.2) mmHg, in subjects treated with placebo, erenumab 70 mg, and 140 mg, respectively. Patients with a notable increase in BP was similar across all treatment groups. In a 24-hour continuous BP assessment, erenumab 70 mg and 140 mg did not increase BP and had no effect ondiurnal rhythm. Conclusions: Selectively blocking the CGRP receptor with erenumab 70 and 140 mg had no relevant effect on BP over 12 weeks versus placebo, and was not associated with significant 24-hour BP changes. Study Supported by: Amgen/Novartis Disclosure: Dr. Tepper has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Alder, Allergan, Amgen, ATI, Avanir, BioVison, Charleston Laboratories, Dr. Reddy’s, electroCore, eNeura, Eli Lilly, GLG, Guidepoint Global, Kimberly-Clark, Pernix, Pfizer, Scion Neurostim, Supernus, Teva, Zosano. Dr. Pascual has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan, Amgen, and Novartis. Dr. Reuter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan, Amgen, Autonomic Technologies, CoLucid, ElectroCore, Novartis, Pharm Allergan; EliLily, TEVA. Dr. Reuter has received research support from Allergan, Amgen, Autonomic Technologies, CoLucid, ElectroCore, Novartis,EliLilly and TEVA. 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. Hong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. 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. 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. Dr. Klatt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Klatt has received compensation for serving on the Board of Directors of Novartis.