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