Table 2.
Summary of clinical efficacy data from phase 3 clinical trials of hypoxia-inducible factor–prolyl hydroxylase inhibitors in patients with anemia and non–dialysis-dependent chronic kidney disease
| Study | Study design; no. of patients | Treatment, duration | Hb response ratea | Mean ΔHb from baseline |
|---|---|---|---|---|
| Daprodustat | ||||
| Kimura et al., 201915 (NCT02791763) | R, OL, AC; ESA-naïve and ESA-treated; n = 299 | DAPRO QDb vs. CERA, 52 wk | Hb at target (11–13 g/dl) during weeks 40–52: DAPRO: 92% CERA: 92% |
Difference in mean Hb (weeks 40–52): 0.10 (95% CI, –0.07 to 0.28) g/dl |
| Enarodustat | ||||
| Akizawa et al., 201978 | R, OL, AC; ESA status NR; n = 216 | ENARO QDc vs. DPO, 24 wk | Hb at target (10–12 g/dl) during weeks 1–24: ENARO: 89.6% DPO: 90.6% |
Difference in mean Hb (weeks 20–24): 0.09 (95% CI, –0.07 to 0.26) g/dl |
| Molidustat | ||||
| MIYABI ND-C86 (NCT03350321) | R, OL, AC; ESA-naïve; n = 161 | MOLI 25 mg QDd vs. DPO, 52 wk | NR | LSM difference in mean Hb (weeks 30–36): –0.38 (95% CI, –0.67 to –0.08) g/dl |
| MIYABI ND-M87 (NCT03350347) | R, OL, AC; ESA-treated; n = 164 | MOLI QDe vs. DPO, 52 wk | Hb at target (11–13 g/dl) during weeks 30–36: MOLI: 80.5% DPO: NR |
LSM difference in mean Hb (weeks 30–36): 0.13 (95% CI, –0.15 to 0.40) g/dl |
| Roxadustat | ||||
| Chen et al., 201923 (NCT02652819) | R, DB, PC; ESA-naïve; n = 152 | ROXA 70 or 100 mg TIWf vs. PBO, 8 wk DB, then 18 wk OL | At week 9: ROXA: 84% PBO: 0% |
During weeks 7–9: ROXA: 1.9 g/dl PBO: –0.4 g/dl (P < 0.001) |
| Akizawa et al., 202088 (NCT02964936) | R, OL, NC; ESA-naïve; n = 99 | ROXA 50 or 70 mg TIWc, 24 wk | From baseline to EOT: Hb at target ≥10 g/dl: ROXA (50 mg): 97.0% ROXA (70 mg): 100.0% Hb at target ≥10.5 g/dl: ROXA (50 mg): 94.9% ROXA (70 mg): 98.0% |
During weeks 18–24: ROXA (50 mg): 1.34 g/dl ROXA (70 mg): 1.30 g/dl |
| Akizawa et al., 202089 | R, OL, AC; ESA-treated; n = 262 | ROXA vs. DPO, 52 wk | Mean Hb during weeks 18–24: ROXA: 11.14 g/dl |
Difference in mean Hb (weeks 18–24): –0.07 g/dl |
| ALPS90 (NCT01887600) | R, DB, PC; ESA-naïve; n = 594 | ROXA vs. PBO, 52–104 wk | NR | During weeks 28–52: ROXA: 1.99 g/dl PBO: 0.41 g/dl (P < 0.001) |
| ANDES91 (NCT01750190) | R, DB, PC; ESA-naïve; n = 922 | ROXA TIWc vs. PBO, 52 wk | During weeks 1–24: ROXA: 86.0% PBO: 6.6% (P = 0.0007) |
During weeks 28–52: ROXA: 2.00 g/dl PBO: 0.16 g/dl (P < 0.0001) |
| OLYMPUS92 (NCT02174627) | R, DB, PC; ESA-naïve; n = 2781 | ROXA 70 mg TIWg vs. PBO, 52 wk | During weeks 1–24: ROXA: 77.0% PBO: 8.5% (P < 0.001) |
During weeks 28–52: ROXA: 1.75 g/dl PBO: 0.40 g/dl (P < 0.001) |
| DOLOMITES93 (NCT02021318) | R, OL, AC; ESA-naïve; n = 616 | ROXA TIW vs. DPO, 104 wk | During weeks 1–24h: ROXA: 89.5% DPO: 78.0% |
NR |
| Vadadustat | ||||
| Nangaku et al., 201919 (NCT03329196) | R, OL, AC; ESA-naïve and ESA-treated; n = 304 | VADA 300 mg QD, then 150–600 mg QDd vs. DPO, 52 wk | NR | LSM of average Hb (weeks 20 and 24): VADA: 11.66 g/dl DPO: 11.93 g/dl |
| PRO2TECT94 (NCT02648347) | R, OL, AC; ESA-naïve; n = 1751 | VADA QD vs. DPO, 52 wk | NR | Difference (VADA vs. DPO): weeks 24–36: 0.05 g/dl weeks 40–52: 0.04 g/dl |
| PRO2TECT94 (NCT02680574) | R, OL, AC; ESA-treated; n = 1725 | VADA QD vs. DPO, 52 wk | NR | Difference (VADA vs. DPO): weeks 24–36: –0.01 g/dl weeks 40–52: 0.00 g/dl |
AC, active controlled; CERA, continuous erythropoietin receptor activator (epoetin beta pegol); CI, confidence interval; DAPRO, daprodustat; DB, double blind; DPO, darbepoetin alfa; ENARO, enarodustat; EOT, end of treatment; ESA, erythropoiesis-stimulating agent; Hb, hemoglobin; LSM, least-squares mean; MOLI, molidustat; NC, noncomparative; NR, not reported; OL, open label; PBO, placebo; PC, PBO controlled; QD, once daily; R, randomized; ROXA, roxadustat; TIW, 3 times weekly; VADA, vadadustat.
ESA-naïve is defined as no use of ESA for a study-defined time period before start of study.
Defined as the proportion of patients with an increase in Hb from baseline of ≥1 g/dl, unless defined otherwise.
Started at 2 and 4 mg QD in ESA-naïve patients with baseline Hb 9 to <11 and 8 to <9 g/dl, respectively, and 4 mg QD in ESA-treated patients with baseline Hb 9 to 13 g/dl; dose adjusted to maintain Hb levels of 11 to 12 g/dl.
Dose adjusted to achieve and maintain Hb levels of 10 to 12 g/dl.
Dose adjusted to achieve and maintain Hb levels of 11 to 13 g/dl.
Starting dose based on prior ESA dose; dose adjusted to achieve and maintain Hb levels of 11 to 13 g/dl.
Weight-based dosing (>40–60 or ≥60 kg), adjusted every 4 weeks to maintain Hb levels of 10 to 12 g/dl.
Tiered, weight-based dosing.
Hb response defined as Hb ≥11 g/dl and an increase in Hb from baseline of ≥1 g/dl in patients with baseline Hb >8 g/dl or ≥2 g/dl in patients with baseline Hb ≤8 g/dl.