Comparative Safety Assessment of Ofatumumab using Data from ASCLEPIOS I/II versus a Historical Propensity-adjusted Placebo Arm (2221)

Objective: To retrospectively compare incidence of common ofatumumab-associated adverse events (AEs) observed in the ASCLEPIOS I/II studies versus historical placebo arm using propensity-score (PS) adjustments. Background: Ofatumumab 20mg subcutaneous is an FDA-approved fully-human anti-CD20 treatment for relapsing forms of multiple sclerosis (RMS). In ASCLEPIOS I/II, ofatumumab was tested against a first-line active comparator (teriflunomide), and establishing causality was not always possible since no placebo incidence was available. Design/Methods: This retrospective analysis compared ofatumumab safety data from ASCLEPIOS I/II (2015–2019) population versus a PS-adjusted historical placebo arm from the fingolimod Phase 3 clinical program (2006–2009) in RMS. For comparability between arms, PS for the most relevant confounders were applied and adjusted for race, region, sex, age, prior MS therapy, duration of MS since first symptom, medical history of specific event of interest, and baseline EDSS. PS were included as weight using IPTW method to generate odds ratios (ORs) for each safety outcome. Results: This analysis was based on 1719 patients (ofatumumab [n=946]; placebo [n=773] from fingolimod program); mean patient treatment exposure was comparable between groups (1.6 years both). PS-adjusted IPTW estimates indicated that ofatumumab was associated with a lower risk of upper respiratory tract infections (OR [95% CI]: 0.7 [0.6; 0.8]), herpes viral infections (0.8 [0.5; 1.2]), insomnia (0.9 [0.5; 1.3]), headache (0.6 [0.5; 0.8]), and depression (0.8 [0.6; 1.2]) versus placebo. While estimates for urinary tract infections (1.0 [0.8; 1.4] and back pain (1.1 [0.7; 1.5]) suggested no additional risk associated with ofatumumab except anxiety events (1.5 [1.0; 2.4]) tended to be more versus placebo possibly due to overreporting of AEs related to specific assessments in Phase 3 studies (ASCLEPIOS I&II), which were not conducted in fingolimod clinical program. Conclusions: Results suggest that majority of the AEs commonly observed with ofatumumab in ASCLEPIOS I/II studies, occur at a lower rate compared to those on placebo. Disclosure: AYAN DAS GUPTA has nothing to disclose. Ratnakar Pingili has received personal compensation for serving as an employee of Novartis. Dieter Haering has received personal compensation for serving as an employee of Novartis. Valentine Jehl has received personal compensation for serving as an employee of Novartis Pharma AG.