Changes in annualized rates of VOEs and annualized SCD-related hospital admission days (intention-to-treat, per protocol set, and strict per protocol set analyses). (A) The annualized rate of VOEs reduced significantly from 1.33 ± 1.32 to 0.64 ± 0.87 (P = .0489) in the patients with SCD treated with mitapivat when combining the study drug treatment periods of the dose-finding period and the fixed-dose extension period in the intention-to-treat analysis. In the other efficacy analyses of the fixed-dose extension period including the (strict) per protocol set analyses, also with documented compliance ≥80% in the week before the event (on the right), this trend was also seen, although nonsignificantly. (B) The annualized SCD-related hospital admission days also reduced, although nonsignificantly, in all efficacy analyses. Means are presented. Error bars represent standard errors of the mean; ∗P < .05. DFP, 8-week dose-finding period; FDEP, 1-year fixed-dose extension period; ITT, intention-to-treat; PPS, per protocol set (all patients who were dosed and had Hb and oxygen gradient ektacytometry assessments at the start of the FDEP and week 52); SPPS, strict per protocol set (all patients of the PPS who were study drug compliant).