Safety, Tolerability and Pharmacokinetics of Crenezumab in Mild-to-Moderate AD Patients Treated with Escalating Doses for up to 32.3 Months (P6.182)

Objective: To assess the long-term safety and tolerability of crenezumab, as well as serum pharmacokinetics, in patients with mild-to-moderate Alzheimer’s disease (AD). Background: Crenezumab is a humanized anti-amyloid beta monoclonal antibody in development for the treatment of AD. This study (GN29632) was designed to evaluate the safety and tolerability of crenezumab at doses up to 120 mg/kg IV q4w. A secondary objective was to characterize the serum pharmacokinetics of crenezumab at the doses investigated. Exploratory objectives assessed clinical efficacy and effects on imaging and plasma biomarkers. Design/Methods: Mild-to-moderate AD patients (50–90 years-old) with an amyloid-positive PET scan were enrolled in 3 consecutive cohorts administering 4 infusions of 30 or 45 (cohort 1, n=26), 60 (cohort 2, n=26), or 120 mg/kg (cohort 3, n=23) IV q4w crenezumab, or corresponding placebo (5:1 ratio). Following the double-blind placebo-controlled portion of the study, patients were offered to continue on active drug at the dose assigned at randomization, except for cohort 3 patients who would receive 60 mg/kg. Recently, the protocol was amended to now offer 60 mg/kg IV q4w to all patients in the active extension. All patients undergo regular brain MRI to monitor for ARIA-E and ARIA-H. Results: Safety and tolerability data collected as of 30 November 2017, and PK data will be presented: patients will have been exposed to crenezumab for up to 32.3, 27.8 or 17.5 months in cohorts 1, 2, and 3 respectively. Conclusions: The long-term safety and tolerability of crenezumab is evaluated in mild-to-moderate AD patients. Updated safety and crenezumab serum concentration data will be presented. Disclosure: Dr. Lin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Schneider has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Quartino has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Bittner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Hu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Cho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Ostrowitzki has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech.