Primary Efficacy Endpoint
Duration of effect as assessed by the primary efficacy variable increased with increasing dose of INCO (for Kaplan-Meier curves, see Figure 2). The median duration of ≥1 point improvement from baseline was 175 days (25 weeks) for the 20U group, 185 days (26 weeks) for the 50U group, 210 days (30 weeks) for the 75U group, and 215 days (31 weeks) for the 100U group (see Table 2 for median durations with 95% CIs).
Pairwise comparisons of dose groups based on hazard ratios (HRs) from Cox proportional hazard regression performed over the entire 360-day follow-up period indicated significantly longer duration of effect for 100U vs 20U INCO (HR=0.56 [95% CI 0.38, 0.83]; P=0.0035) and for 100U vs 50U (HR=0.55 [95% CI 0.37, 0.81]; P=0.0023) despite the study not being powered for confirmatory statistical significance testing between the dose groups.
Secondary and Other Efficacy Endpoints
The median duration of an effect defined as FWS score of none (0) or mild (1) at maximum frown and as 2-point improvement on the FWS for each INCO dose group is shown in Table 2. In line with the primary efficacy variable, both secondary duration of effect variables consistently increased with increasing dose. For the response rate defined as ≥ 1 point improvement as determined by the investigator (Figure 3, top) and subject (Figure 3, bottom), there was a clear dose-response relationship across INCO dose groups with increasing doses resulting in a greater percentage of responders over time for higher doses.
