Exposure-response relationship
As the subjects were randomized in a 3:1 ratio to receive inebilizumab or placebo treatment in the RCP of N‑MOmentum, inebilizumab-treated subjects were grouped by tertiles based on the PK exposure (low, medium, and high) to achieve a comparable sample size to the placebo group for time-to-event analysis. Three PK metrics, namely area under the concentration-time curve following the first dose (AUC0-14d), the cumulative AUC to the last observation in the RCP (AUCcumulative), and the systemic clearance (CL) of the first‑order elimination pathway, were obtained from the population PK modeling. The relationship between PK exposure and the primary efficacy endpoint (AC-determined NMOSD attack) was evaluated by comparing the efficacy outcome of inebilizumab-treated subjects of low, medium and high PK exposure with placebo in RCP. In addition, a statistically significant improvement with inebilizumab compared to placebo as demonstrated by three key secondary endpoints: worsening from baseline to the last visit of the RCP in Expanded Disability Severity Scale, cumulative total active MRI lesions during the RCP, and number of NMOSD-related in-patient hospitalizations during the RCP.
Potential impacts of body weight, a known PK covariate for therapeutic monoclonal antibodies, and the presence of anti-drug antibodies (ADA) were also assessed on the efficacy outcomes of the pivotal study.
Results