Fig. 4.
Change in mean CXM by individual mean AUC in the phase II and III studies. (a) Points represent the individual mean CXM from day 10 to day 183 of the phase II study and individual mean vosoritide AUC0-t, color-coded by study cohort (C1: Cohort 1, 2.5 µg/kg; C2: Cohort 2, 7.5 µg/kg; C3: Cohort 3, 15 µg/kg; C4: Cohort 4, 30 µg/kg). One patient had a high individual mean AUC0-t (4.28 × 106 pg-min/mL) relative to other patients, but a within-range mean CXM (12,200 pg/mL). This patient was included in the fit through the data but was not included in this figure. b Points represent the individual mean CXM from day 10 to month 24 of the phase II study and individual mean vosoritide AUC0-60min, color-coded by study cohort (C3: Cohort 3, 15 µg/kg; C4: Cohort 4, 30 µg/kg). c Points represent the individual mean CXM from week 13 to week 52 in the phase III study and individual mean vosoritide AUC0-60min. Solid lines represent the fits through the data and the shaded regions represent the 95% confidence intervals. The respective analyses using the individual mean vosoritide Cmax are similar and are shown in Fig. S6 in the ESM. AUC0-t area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, AUC0-60min area under the plasma concentration-time curve from time zero to 60 min postdose, CXM collagen type X marker, Cmax maximum observed plasma concentration, ESM electronic supplementary material