Changes from baseline in hematologic, biochemical, oxygen affinity (p50), sickling kinetics (t50), and pharmacodynamics in response to mitapivat at various longitudinal time points
| . | Baseline . | Week 4 Change from baseline . | Week 12 Change from baseline . | Week 24 Change from baseline . | Week 48 (1 year) Change from baseline . | Week 72 Change from baseline . | Week 96 Change from baseline . | Week 108 Change from baseline . | Week 120 Change from baseline . | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n . | Mean (SD) . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | |
| Hb (g/dL) | 15 | 8.63 (1.11) | 15 | 1.16 (0.73) | <.0001 | 14 | 1.26 (0.85) | <.0001 | 15 | 1.38 (0.88) | <.0001 | 13 | 1.13 (1.2) | .0004 | 14 | 1.03 (0.96) | <.0001 | 13 | 0.76 (1.13) | .01 | 12 | 0.89 (1.03) | .002 | 9 | 0.81 (1.03) | .01 |
| ARC (×103/μL) | 15 | 217.21 (88.27) | 15 | −17.23 (68.03) | .31 | 14 | −23.68 (78.25) | .24 | 15 | −10.51 (73.37) | .57 | 13 | 8.98 (82.26) | .68 | 14 | −5.17 (103.92) | .85 | 13 | 14.72 (112.07) | .62 | 12 | 2.27 (67.54) | .9 | 9 | 8.24 (68.99) | .70 |
| LDH (U/L) | 14 | 536.71 (222.16) | 14 | −147.93 (127.85) | <.0001 | 13 | −118.23 (113.8) | <.0001 | 14 | −122.86 (167.28) | .004 | 12 | −120.25 (178.83) | .01 | 13 | −180.08 (175.89) | .0001 | 12 | −138.42 (177.54) | .005 | 11 | −189.91 (216.12) | .002 | 8 | −84.50 (197.01) | .19 |
| AST (U/L) | 15 | 39.67 (15.01) | 15 | 0.13 (17.15) | .98 | 14 | −3.71 (8.29) | .08 | 15 | −2.93 (9.84) | .23 | 13 | −0.38 (13.1) | .91 | 14 | −0.93 (14.17) | .8 | 13 | 2.38 (15.89) | .57 | 12 | −1.42 (13.49) | .7 | 9 | 5.89 (6.51) | .004 |
| T. Bili (mg/dL) | 15 | 2.73 (1.43) | 15 | −0.91 (0.85) | <.0001 | 14 | −1.03 (1.01) | <.0001 | 15 | −0.94 (1.05) | .0003 | 13 | −0.84 (1.41) | .03 | 14 | −1.09 (1.22) | .0005 | 13 | −0.75 (1.31) | .03 | 12 | −1.16 (1.34) | .002 | 9 | −0.83 (1.48) | .07 |
| p50 (torr) | 15 | 32.91 (3.44) | 13 | −8.94 (9.59) | .0005 | 14 | −12.78 (12.01) | <.0001 | 13 | −9.37 (10.78) | .001 | 13 | −9.61 (9.59) | .0002 | 14 | −13.56 (10.14) | <.0001 | 13 | −13.67 (13.86) | .0002 | 8 | −13.08 (12.10) | .001 | |||
| t50 (min) | 13 | 159.58 (89.47) | 13 | 26.93 (36.17) | .005 | 12 | 48.56 (59.16) | .003 | 13 | 38.89 (77.21) | .06 | 11 | 25.36 (71.52) | .22 | 12 | 53.17 (173.68) | .27 | 11 | 12.19 (54.01) | .43 | 6 | 8.62 (75.84) | .76 | |||
| 2,3-DPG (μg/mL) | 15 | 16.98 (1.83) | 15 | −25.08 (10.17) | <.0001 | 14 | −21.53 (11.67) | <.0001 | 14 | −22.46 (12.34) | <.0001 | 13 | −17.55 (13.69) | <.0001 | 14 | −12.95 (18.75) | .007 | 13 | −12.12 (20.09) | .02 | 8 | −17.46 (20.78) | .01 | |||
| ATP (μg/mL) | 15 | 7.93 (1.03) | 15 | 26.17 (11.27) | <.0001 | 14 | 25.48 (19.36) | <.0001 | 14 | 14.35 (22.78) | .01 | 13 | 26.15 (25.22) | <.0001 | 14 | 36.6 (19.61) | <.0001 | 13 | 37.25 (16.71) | <.0001 | 8 | 44.09 (18.61) | <.0001 | |||
| ATP:2,3-DPG ratio | 15 | 0.47 (0.06) | 15 | 71.07 (25.41) | <.0001 | 14 | 60.34 (15.89) | <.0001 | 14 | 49.73 (32.68) | <.0001 | 13 | 55.71 (36.98) | <.0001 | 14 | 62.66 (39.38) | <.0001 | 13 | 62.7 (37.46) | <.0001 | 8 | 85.22 (60.92) | <.0001 | |||
| . | Baseline . | Week 4 Change from baseline . | Week 12 Change from baseline . | Week 24 Change from baseline . | Week 48 (1 year) Change from baseline . | Week 72 Change from baseline . | Week 96 Change from baseline . | Week 108 Change from baseline . | Week 120 Change from baseline . | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n . | Mean (SD) . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | n . | Mean (SD) . | P value . | |
| Hb (g/dL) | 15 | 8.63 (1.11) | 15 | 1.16 (0.73) | <.0001 | 14 | 1.26 (0.85) | <.0001 | 15 | 1.38 (0.88) | <.0001 | 13 | 1.13 (1.2) | .0004 | 14 | 1.03 (0.96) | <.0001 | 13 | 0.76 (1.13) | .01 | 12 | 0.89 (1.03) | .002 | 9 | 0.81 (1.03) | .01 |
| ARC (×103/μL) | 15 | 217.21 (88.27) | 15 | −17.23 (68.03) | .31 | 14 | −23.68 (78.25) | .24 | 15 | −10.51 (73.37) | .57 | 13 | 8.98 (82.26) | .68 | 14 | −5.17 (103.92) | .85 | 13 | 14.72 (112.07) | .62 | 12 | 2.27 (67.54) | .9 | 9 | 8.24 (68.99) | .70 |
| LDH (U/L) | 14 | 536.71 (222.16) | 14 | −147.93 (127.85) | <.0001 | 13 | −118.23 (113.8) | <.0001 | 14 | −122.86 (167.28) | .004 | 12 | −120.25 (178.83) | .01 | 13 | −180.08 (175.89) | .0001 | 12 | −138.42 (177.54) | .005 | 11 | −189.91 (216.12) | .002 | 8 | −84.50 (197.01) | .19 |
| AST (U/L) | 15 | 39.67 (15.01) | 15 | 0.13 (17.15) | .98 | 14 | −3.71 (8.29) | .08 | 15 | −2.93 (9.84) | .23 | 13 | −0.38 (13.1) | .91 | 14 | −0.93 (14.17) | .8 | 13 | 2.38 (15.89) | .57 | 12 | −1.42 (13.49) | .7 | 9 | 5.89 (6.51) | .004 |
| T. Bili (mg/dL) | 15 | 2.73 (1.43) | 15 | −0.91 (0.85) | <.0001 | 14 | −1.03 (1.01) | <.0001 | 15 | −0.94 (1.05) | .0003 | 13 | −0.84 (1.41) | .03 | 14 | −1.09 (1.22) | .0005 | 13 | −0.75 (1.31) | .03 | 12 | −1.16 (1.34) | .002 | 9 | −0.83 (1.48) | .07 |
| p50 (torr) | 15 | 32.91 (3.44) | 13 | −8.94 (9.59) | .0005 | 14 | −12.78 (12.01) | <.0001 | 13 | −9.37 (10.78) | .001 | 13 | −9.61 (9.59) | .0002 | 14 | −13.56 (10.14) | <.0001 | 13 | −13.67 (13.86) | .0002 | 8 | −13.08 (12.10) | .001 | |||
| t50 (min) | 13 | 159.58 (89.47) | 13 | 26.93 (36.17) | .005 | 12 | 48.56 (59.16) | .003 | 13 | 38.89 (77.21) | .06 | 11 | 25.36 (71.52) | .22 | 12 | 53.17 (173.68) | .27 | 11 | 12.19 (54.01) | .43 | 6 | 8.62 (75.84) | .76 | |||
| 2,3-DPG (μg/mL) | 15 | 16.98 (1.83) | 15 | −25.08 (10.17) | <.0001 | 14 | −21.53 (11.67) | <.0001 | 14 | −22.46 (12.34) | <.0001 | 13 | −17.55 (13.69) | <.0001 | 14 | −12.95 (18.75) | .007 | 13 | −12.12 (20.09) | .02 | 8 | −17.46 (20.78) | .01 | |||
| ATP (μg/mL) | 15 | 7.93 (1.03) | 15 | 26.17 (11.27) | <.0001 | 14 | 25.48 (19.36) | <.0001 | 14 | 14.35 (22.78) | .01 | 13 | 26.15 (25.22) | <.0001 | 14 | 36.6 (19.61) | <.0001 | 13 | 37.25 (16.71) | <.0001 | 8 | 44.09 (18.61) | <.0001 | |||
| ATP:2,3-DPG ratio | 15 | 0.47 (0.06) | 15 | 71.07 (25.41) | <.0001 | 14 | 60.34 (15.89) | <.0001 | 14 | 49.73 (32.68) | <.0001 | 13 | 55.71 (36.98) | <.0001 | 14 | 62.66 (39.38) | <.0001 | 13 | 62.7 (37.46) | <.0001 | 8 | 85.22 (60.92) | <.0001 | |||
Mean change was calculated from baseline (before drug initiation) and was reported as change for clinical laboratory measures (first 5 rows) and as percent change for p50 and t50, 2,3-DPG, ATP, and ATP:2,3-DPG ratio (last 5 rows). 2,3-DPG and ATP levels used in analyses were corrected for hematocrit. After week 96, collection of exploratory markers (p50, t50, 2,3-DPG, and ATP) took place less often, every 6 months. For data beyond week 120 refer to Supplemental Table 2.
ARC, absolute reticulocyte count; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; T. Bili, total bilirubin.