Table 3.
Summary of clinical efficacy data from phase 3 clinical trials of hypoxia-inducible factor–prolyl hydroxylase inhibitors in patients with anemia and dialysis-dependent chronic kidney disease
| Study | Study design; no. of patients | Treatment, duration | Hb response ratea | Mean ΔHb from baseline |
|---|---|---|---|---|
| Daprodustat | ||||
| Tsubakihara et al., 201913 (NCT02829320) | OL, NC; ESA-naïve, I-HD and M-HD; n = 28 | DAPRO 4 mg QDb, 24 wk | During weeks 1–4: 39% |
After 4 weeks: 0.79 g/dl |
| Akizawa et al., 202014 (NCT02969655) | R, DB, AC; ESA-treated, M-HD; n = 271 | DAPRO 4 mg QDb vs. DPO, 52 wk | Hb within target range (10–12 g/dl) during weeks 40–52: DAPRO: 88% DPO: 90% |
During weeks 40–52: DAPRO: 0.0 g/dl DPO: 0.0 g/dl Adjusted difference vs. DPO: 0.1 (95% CI, –0.1 to 0.2) g/dl |
| Enarodustat | ||||
| Akizawa et al., 201977 | R, DB, AC; ESA-treated, M-HD; n = 173 | ENARO QDc vs. DPO; 24 wk | Hb within target range (10–12 g/dl) during weeks 1–24: ENARO: 78.2% DPO: 88.8% |
Difference in mean Hb (weeks 20–24): –0.12 (–0.33 to 0.10) g/dl |
| Molidustat | ||||
| MIYABI HD-M95 (NCT03543657) | R, DB, AC; ESA-treated, M-HD; n = 229 | MOLI 5–200 mg QDb vs. DPO; 52 wk | NR | LSM difference in Hb change from baseline (weeks 33–36): –0.13 g/dl |
| Roxadustat | ||||
| Chen et al., 201922 (NCT02652806) | R, OL, AC; ESA-treated, M-DD; n = 304 | ROXA 100 or 120 mg TIWd vs. Epoetin alfa, 26 wk | During weeks 23–27: ROXA: 92.5% Epoetin alfa: 92.5% |
During weeks 23–27: ROXA: 0.7 g/dl Epoetin alfa: 0.5 g/dl Difference vs. Epoetin alfa: 0.2 (95% CI, –0.02 to 0.5) g/dl |
| Akizawa et al., 202016 (NCT02779764, NCT02780141) | R, OL, NC; ESA-naïve (I-HD) and ESA-treated (M-HD); n = 239 | ESA-naïve: ROXA 50 or 70 mg TIWd, 24 wk ESA-treated: ROXA 70 or 100 mg TIWe, 52 wk |
From baseline to EOTf: ESA-naïve: 87.8% ESA-treated: NR |
During weeks 18–24: ESA-naïve: 2.26 g/dl ESA-treated: –0.03 g/dl During weeks 46–52: ESA-treated: 0.12 g/dl |
| Akizawa et al., 202017 (NCT02780726) | R, OL, NC; ESA-naïve and ESA-treated, PD (>4 wk); n = 56 | ROXA 50 or 70 mg TIW (ESA-naïve) or ROXA 70 or 100 mg (ESA-treated), 24 wk | Hb within target range (10–12 g/dl) during weeks 18–24: ESA-naïve: 92.3% ESA-treated: 74.4% |
During weeks 18–24: ESA-naïve: 1.69 g/dl ESA-treated: 0.14 g/dl |
| Akizawa et al., 202018 (NCT02952092) | R, DB, AC; ESA-treated, M-HD; n = 303 | ROXA 70 or 100 mg TIW vs. DPO QW, 24 wk | Hb within target range (10–12 g/dl) during weeks 18–24: ROXA: 95.2% DPO: 91.3% |
During weeks 18–24: ROXA: –0.04 g/dl DPO: –0.03 g/dl Difference vs. DPO: –0.02 (95% CI, –0.18 to 0.15) g/dl |
| HIMALAYAS96 (NCT02052310) | R, OL, AC, ESA-naïve and ESA-limited use, I-DD; n = 1043 | ROXA TIW vs. Epoetin alfa, 52 wk | During weeks 1–24: ROXA: 88.2% Epoetin alfa: 84.4% |
During weeks 28–52: ROXA: 2.57 g/dl Epoetin alfa: 2.36 g/dl (P< 0.001 vs. Epoetin alfa) |
| PYRENEES90 (NCT02278341) | R, OL, AC, ESA-treated, M-DD; n = 836 | ROXA 100, 150, or 200 mg TIWe vs. ESA, 52–104 wk | NR | During weeks 28–52: ROXA: 0.40 g/dl ESA: 0.18 g/dl (P < 0.001 vs. ESA) |
| ROCKIES97 (NCT02174731) | R, OL, AC; ESA-naïve and ESA-treated, M-DD and I-DD (n = 416); total n = 2133 | ROXA TIWg vs. Epoetin alfa, 52 wk | Proportion of time with Hb ≥10 g/dl during weeks 28–52: ROXA: 79% Epoetin alfa: 76% |
During weeks 28–52: ROXA: 0.77 g/dl Epoetin alfa: 0.68 g/dl (P < 0.05 vs. Epoetin alfa) |
| SIERRAS98 (NCT02273726) | R, OL, AC; ESA-treated, M-DD and I-DD (n = 371); total n = 741 | ROXA TIWh vs. Epoetin alfa, 52 wk | NR | During weeks 28–52: ROXA: 0.39 g/dl Epoetin alfa: –0.09 g/dl (P < 0.0001 vs. Epoetin alfa) |
| Vadadustat | ||||
| Nangaku et al., 201920 (NCT03439137) | R, DB, AC; ESA-treated, M-HD; n = 323 | VADA 300 mg QD, then 150–600 mgb vs. DPO, 52 wk | Hb within target range (10–12 g/dl) at week 24: VADA: 75.4% DPO: 75.7% |
LSM of average Hb (weeks 20 and 24): VADA: 10.61 g/dl DPO: 10.65 g/dl |
| INNO2VATE99 (NCT02865850) | R, DB, AC; ESA-naïve and ESA-treated; I-DD; n = 369 | VADA vs. DPO, 52 wk | NR | LSM difference in Hb change: During weeks 24–36: –0.3 g/dl During weeks 40–52: –0.07 g/dl |
| INNO2VATE99 (NCT02892149) | R, DB, AC; ESA-naïve and ESA-treated; M-DD; n = 3554 | VADA vs. DPO, 52 wk | NR | LSM difference in Hb change: During weeks 24–36: –0.17 g/dl During weeks 40–52: –0.18 g/dl |
AC, active controlled; CI, confidence interval; DAPRO, daprodustat; DB, double blind; DPO, darbepoetin alfa; ENARO, enarodustat; EOT, end of treatment; ESA, erythropoietin-stimulating agent; Hb, hemoglobin; I-DD, incident dialysis (hemodialysis and PD); I-HD, incident hemodialysis; LSM, least-squares mean; M-DD, maintenance/stable dialysis (hemodialysis and PD); M-HD, maintenance/stable hemodialysis; MOLI, molidustat; NC, noncomparative; NR, not reported; OL, open label; PD, peritoneal dialysis; QD, once daily; QW, once weekly; R, randomized; ROXA, roxadustat; TIW, 3 times weekly; VADA, vadadustat.
Defined as the proportion of patients with an increase in Hb from baseline of ≥1.0 g/dl, unless defined otherwise.
Titrated to maintain Hb levels of 10 to 12 g/dl.
Weight-based dosing (>45–60 or ≥60 kg), adjusted to maintain Hb levels of 10 to 12 g/dl.
Starting dose based on study site, weight, and 2 most recent Hb measurements, adjusted to maintain Hb levels of 10 to 12 g/dl.
Dosed according to average weekly dose of prior ESA therapy, adjusted to maintain Hb levels of 10 to 12 g/dl.
Hb response defined as the proportion of patients with Hb of ≥10 g/dl and an increase in Hb from baseline of ≥1.0 g/dl.
Titrated to achieve an Hb level of 11 g/dl and to maintain Hb levels of 10 to 12 g/dl.
Initially dosed according to prior dose of erythropoietin therapy.