| Study . | Comparator . | Patients, n . | CKD stage . | Treatment period (weeks) . | Target Hb (g/dl) . | Efficacy endpoints . | Safety endpoints . |
|---|---|---|---|---|---|---|---|
| Roxadustat (vs ESAs) | |||||||
| DOLOMITES [60] (Europe) | Darbepoetin alfa | 616 | 3–5 | 104 | 10–12 | Patients with Hb response at 24 weeks: 89.5% vs 78.0% Mean monthly IV iron use at 1–36 weeks: 34.7 vs 69.6 mg Time to first use of IV iron at 1–36 weeks: HR 0.46 (95% CI 0.26–0.78) | MACE: 11.8% vs 14.0% [HR 0.81 (95% CI 0.52–1.25)] MACE+: 16.7% vs 18.1% [HR 0.90 (95% CI 0.61–1.32)] VTE: 2.5% vs 0.7% [HR 3.63 (95% CI 0.76–17.20)] |
| Akizawa et al. [61] (Japan) | Darbepoetin alfa | 334 | 2–5 | 24 | 10–12 | Mean Hb change at 18–24 weeks: 0.15 vs 0.22 g/dl Patients with target Hb at 18–24 weeks: 77.1% vs 85.5% | Hypertension: 2.3% vs 3.8% Hyperkalaemia: 3.8% vs 3.8% Nasopharyngitis: 19.1% vs 26.0% Retinal haemorrhage: 31.4% vs 39.8% |
| Daprodustat (vs ESAs) | |||||||
| ASCEND-ND [62] (Global) | Darbepoetin alfa | 3872 | 3–5 | 52 | 10–11 | Mean Hb change at 28–52 weeks: 0.74 vs 0.66 g/dl Use of rescue therapy: 2.0% vs 3.3% RBC transfusion: 12.8% vs 3.5% | MACE (ITT analysis): 19.5% vs 19.2% [HR 1.03 (95% CI 0.89–1.19)] MACE (on-treatment analysis): 14.1% vs 10.5% [HR 1.40 (95% CI 1.17–1.68)] Cancer-related death or tumour progression or recurrence: 3.7% vs 2.5% [RR 1.47 (95% CI 1.03–2.10)] Oesophageal or gastric erosions: 3.6% vs 2.1% [RR 1.70 (95% CI 1.16–2.49)] |
| Nangaku et al. [63] (Japan) | Epoetin beta pegol | 299 | 3–5 | 52 | 11–13 | Mean Hb level at 40–52 weeks (ITT): 12.0 vs 11.9 g/dl Patients with target Hb at 40–52 weeks: 92% vs 92% [OR 1.01 (95% CI 0.33–3.04)] | Hypertension: 3.0% vs 5.0% Hyperkalaemia: 8.0% vs 5.0% Nasopharyngitis: 33.0% vs 37.0% |
| Vadadustat (vs ESAs) | |||||||
| PRO2TECT [64] (global) | Darbepoetin alfa | 3476 | 3–5 | 52 | 10–11 (USA) 10–12 (non-USA) | Mean Hb change at 24–36 weeks: 0.74 vs 0.66 g/dl RBC transfusion 24–36 weeks: 2.7% vs 2.2% (ESA untreated), 1.6% vs 1.2% (ESA treated) ESA rescue 24–36 weeks% vs 12.8% (ESA untreated), 5.0% vs 13.4% (ESA treated) | MACE: 22.0% vs 19.9% [HR 1.17 (95% CI 1.01–1.36)] MACE+: 25.9% vs 24.5% [HR 1.11 (95% CI 0.97–1.27)] Hypertension: 17.7% vs 22.1% (ESA untreated), 14.4% vs 14.8% (ESA treated) Hyperkalaemia: 12.3% vs 15.6% (ESA untreated), 9.4% vs 9.9% (ESA treated) |
| Nangaku et al. [65] (Japan) | Darbepoetin alfa | 304 | 3–5 | 52 | 11–13 | Mean Hb level at 20–24 weeks: 11.7 vs 11.9 g/dl Patients with target Hb at 52 weeks: 71.4% vs 84.5% (ESA non-users), 79.2% vs 76.6% (ESA users) | Adverse drug reaction (≥1): 13.2% vs 4.6% Hypertension: 1.3% vs 7.2% Nasopharyngitis: 24.5% vs 28.1% |
| Enarodustat (vs ESAs) | |||||||
| SYMPHONY-ND [67] (Japan) | Darbepoetin alfa | 216 | 3–5 | 24 | 10–12 | Mean Hb level at 20–24 weeks: 10.96 vs 10.87 g/dl Patients with target Hb at 24 weeks: 88.6% vs 87.9% | Retinal disorders: 3.7% vs 0.9% Upper respiratory tract infection: 17.8% vs 22.9% Hypertension: 4.7% vs 4.6% |
| Molidustat vs ESAs | |||||||
| MIYABI ND-C [66] (Japan) | Darbepoetin alfa | 162 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.28 vs 11.70 g/dl Mean Hb change at 30–36 weeks: 1.32 vs 1.69 g/dl Patients with target Hb at 30–36 weeks: 68.3% vs 85.0% Mean IV iron use: 2.89 vs 11.22 mg/week | Serious TEAE: 17.1% vs 7.6% MACE: 7.3% vs 0.0% Hyperkalaemia: 12.2% vs 11.4% Nasopharyngitis: 31.7% vs 26.6% |
| MIYABI ND-M [68] (Japan) | Darbepoetin alfa | 164 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.67 vs 11.53 g/dl Mean Hb change at 30–36 weeks: 0.36 vs 0.24 g/dl Patients with target Hb at 30–36 weeks: 72.0% vs 76.8% | Serious TEAE: 32.9% vs 26.8% MACE: 3.7% vs 1.2% Hyperkalaemia: 2.4% vs 8.5% Hypertension: 2.4% vs 6.1% Diabetic retinopathy: 3.7% vs 1.2% |
| Desidustat (vs ESAs) | |||||||
| DREAM-ND [69] (India and Sri Lanka) | Darbepoetin alfa | 588 | 3–5 | 24 | 10–12 | Mean Hb change at 16–24 weeks: 1.95 vs 1.83 g/dl Mean Hb level at 16–24 weeks: 10.90 vs 10.77 g/dl Patients with Hb response at 24 weeks: 77.8% vs 68.5% Mean hepcidin change at 24 weeks: −12.0 vs 7.8 ng/ml | Serious TEAE: 8.2% vs 6.1% Hypertension: 1.7% vs 5.8% |
| Study . | Comparator . | Patients, n . | CKD stage . | Treatment period (weeks) . | Target Hb (g/dl) . | Efficacy endpoints . | Safety endpoints . |
|---|---|---|---|---|---|---|---|
| Roxadustat (vs ESAs) | |||||||
| DOLOMITES [60] (Europe) | Darbepoetin alfa | 616 | 3–5 | 104 | 10–12 | Patients with Hb response at 24 weeks: 89.5% vs 78.0% Mean monthly IV iron use at 1–36 weeks: 34.7 vs 69.6 mg Time to first use of IV iron at 1–36 weeks: HR 0.46 (95% CI 0.26–0.78) | MACE: 11.8% vs 14.0% [HR 0.81 (95% CI 0.52–1.25)] MACE+: 16.7% vs 18.1% [HR 0.90 (95% CI 0.61–1.32)] VTE: 2.5% vs 0.7% [HR 3.63 (95% CI 0.76–17.20)] |
| Akizawa et al. [61] (Japan) | Darbepoetin alfa | 334 | 2–5 | 24 | 10–12 | Mean Hb change at 18–24 weeks: 0.15 vs 0.22 g/dl Patients with target Hb at 18–24 weeks: 77.1% vs 85.5% | Hypertension: 2.3% vs 3.8% Hyperkalaemia: 3.8% vs 3.8% Nasopharyngitis: 19.1% vs 26.0% Retinal haemorrhage: 31.4% vs 39.8% |
| Daprodustat (vs ESAs) | |||||||
| ASCEND-ND [62] (Global) | Darbepoetin alfa | 3872 | 3–5 | 52 | 10–11 | Mean Hb change at 28–52 weeks: 0.74 vs 0.66 g/dl Use of rescue therapy: 2.0% vs 3.3% RBC transfusion: 12.8% vs 3.5% | MACE (ITT analysis): 19.5% vs 19.2% [HR 1.03 (95% CI 0.89–1.19)] MACE (on-treatment analysis): 14.1% vs 10.5% [HR 1.40 (95% CI 1.17–1.68)] Cancer-related death or tumour progression or recurrence: 3.7% vs 2.5% [RR 1.47 (95% CI 1.03–2.10)] Oesophageal or gastric erosions: 3.6% vs 2.1% [RR 1.70 (95% CI 1.16–2.49)] |
| Nangaku et al. [63] (Japan) | Epoetin beta pegol | 299 | 3–5 | 52 | 11–13 | Mean Hb level at 40–52 weeks (ITT): 12.0 vs 11.9 g/dl Patients with target Hb at 40–52 weeks: 92% vs 92% [OR 1.01 (95% CI 0.33–3.04)] | Hypertension: 3.0% vs 5.0% Hyperkalaemia: 8.0% vs 5.0% Nasopharyngitis: 33.0% vs 37.0% |
| Vadadustat (vs ESAs) | |||||||
| PRO2TECT [64] (global) | Darbepoetin alfa | 3476 | 3–5 | 52 | 10–11 (USA) 10–12 (non-USA) | Mean Hb change at 24–36 weeks: 0.74 vs 0.66 g/dl RBC transfusion 24–36 weeks: 2.7% vs 2.2% (ESA untreated), 1.6% vs 1.2% (ESA treated) ESA rescue 24–36 weeks% vs 12.8% (ESA untreated), 5.0% vs 13.4% (ESA treated) | MACE: 22.0% vs 19.9% [HR 1.17 (95% CI 1.01–1.36)] MACE+: 25.9% vs 24.5% [HR 1.11 (95% CI 0.97–1.27)] Hypertension: 17.7% vs 22.1% (ESA untreated), 14.4% vs 14.8% (ESA treated) Hyperkalaemia: 12.3% vs 15.6% (ESA untreated), 9.4% vs 9.9% (ESA treated) |
| Nangaku et al. [65] (Japan) | Darbepoetin alfa | 304 | 3–5 | 52 | 11–13 | Mean Hb level at 20–24 weeks: 11.7 vs 11.9 g/dl Patients with target Hb at 52 weeks: 71.4% vs 84.5% (ESA non-users), 79.2% vs 76.6% (ESA users) | Adverse drug reaction (≥1): 13.2% vs 4.6% Hypertension: 1.3% vs 7.2% Nasopharyngitis: 24.5% vs 28.1% |
| Enarodustat (vs ESAs) | |||||||
| SYMPHONY-ND [67] (Japan) | Darbepoetin alfa | 216 | 3–5 | 24 | 10–12 | Mean Hb level at 20–24 weeks: 10.96 vs 10.87 g/dl Patients with target Hb at 24 weeks: 88.6% vs 87.9% | Retinal disorders: 3.7% vs 0.9% Upper respiratory tract infection: 17.8% vs 22.9% Hypertension: 4.7% vs 4.6% |
| Molidustat vs ESAs | |||||||
| MIYABI ND-C [66] (Japan) | Darbepoetin alfa | 162 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.28 vs 11.70 g/dl Mean Hb change at 30–36 weeks: 1.32 vs 1.69 g/dl Patients with target Hb at 30–36 weeks: 68.3% vs 85.0% Mean IV iron use: 2.89 vs 11.22 mg/week | Serious TEAE: 17.1% vs 7.6% MACE: 7.3% vs 0.0% Hyperkalaemia: 12.2% vs 11.4% Nasopharyngitis: 31.7% vs 26.6% |
| MIYABI ND-M [68] (Japan) | Darbepoetin alfa | 164 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.67 vs 11.53 g/dl Mean Hb change at 30–36 weeks: 0.36 vs 0.24 g/dl Patients with target Hb at 30–36 weeks: 72.0% vs 76.8% | Serious TEAE: 32.9% vs 26.8% MACE: 3.7% vs 1.2% Hyperkalaemia: 2.4% vs 8.5% Hypertension: 2.4% vs 6.1% Diabetic retinopathy: 3.7% vs 1.2% |
| Desidustat (vs ESAs) | |||||||
| DREAM-ND [69] (India and Sri Lanka) | Darbepoetin alfa | 588 | 3–5 | 24 | 10–12 | Mean Hb change at 16–24 weeks: 1.95 vs 1.83 g/dl Mean Hb level at 16–24 weeks: 10.90 vs 10.77 g/dl Patients with Hb response at 24 weeks: 77.8% vs 68.5% Mean hepcidin change at 24 weeks: −12.0 vs 7.8 ng/ml | Serious TEAE: 8.2% vs 6.1% Hypertension: 1.7% vs 5.8% |
Table 2 outlines details of phase 3 comparator trials with ESA therapy, including two roxadustat (one from Europe [60] and one from Japan [61]), two daprodustat (one global [62] and one from Japan [63]), two vadadustat (one global [64] and one from Japan [65]), two molidustat (Japan [66, 68]), one enarodustat (Japan [67]) and one desidustat (South Asia [69]).
Hb: haemoglobin; ITT: intention to treat; OR: odds ratio; MACE: major adverse cardiac event (composite of death, non-fatal MI and/or stroke); MACE+: expanded major adverse cardiac event (MACE plus hospitalization for either heart failure or unstable angina or MACE plus hospitalization for either HF or a thromboembolic event); TEAE: treatment emergent adverse event; vs: versus.
| Study . | Comparator . | Patients, n . | CKD stage . | Treatment period (weeks) . | Target Hb (g/dl) . | Efficacy endpoints . | Safety endpoints . |
|---|---|---|---|---|---|---|---|
| Roxadustat (vs ESAs) | |||||||
| DOLOMITES [60] (Europe) | Darbepoetin alfa | 616 | 3–5 | 104 | 10–12 | Patients with Hb response at 24 weeks: 89.5% vs 78.0% Mean monthly IV iron use at 1–36 weeks: 34.7 vs 69.6 mg Time to first use of IV iron at 1–36 weeks: HR 0.46 (95% CI 0.26–0.78) | MACE: 11.8% vs 14.0% [HR 0.81 (95% CI 0.52–1.25)] MACE+: 16.7% vs 18.1% [HR 0.90 (95% CI 0.61–1.32)] VTE: 2.5% vs 0.7% [HR 3.63 (95% CI 0.76–17.20)] |
| Akizawa et al. [61] (Japan) | Darbepoetin alfa | 334 | 2–5 | 24 | 10–12 | Mean Hb change at 18–24 weeks: 0.15 vs 0.22 g/dl Patients with target Hb at 18–24 weeks: 77.1% vs 85.5% | Hypertension: 2.3% vs 3.8% Hyperkalaemia: 3.8% vs 3.8% Nasopharyngitis: 19.1% vs 26.0% Retinal haemorrhage: 31.4% vs 39.8% |
| Daprodustat (vs ESAs) | |||||||
| ASCEND-ND [62] (Global) | Darbepoetin alfa | 3872 | 3–5 | 52 | 10–11 | Mean Hb change at 28–52 weeks: 0.74 vs 0.66 g/dl Use of rescue therapy: 2.0% vs 3.3% RBC transfusion: 12.8% vs 3.5% | MACE (ITT analysis): 19.5% vs 19.2% [HR 1.03 (95% CI 0.89–1.19)] MACE (on-treatment analysis): 14.1% vs 10.5% [HR 1.40 (95% CI 1.17–1.68)] Cancer-related death or tumour progression or recurrence: 3.7% vs 2.5% [RR 1.47 (95% CI 1.03–2.10)] Oesophageal or gastric erosions: 3.6% vs 2.1% [RR 1.70 (95% CI 1.16–2.49)] |
| Nangaku et al. [63] (Japan) | Epoetin beta pegol | 299 | 3–5 | 52 | 11–13 | Mean Hb level at 40–52 weeks (ITT): 12.0 vs 11.9 g/dl Patients with target Hb at 40–52 weeks: 92% vs 92% [OR 1.01 (95% CI 0.33–3.04)] | Hypertension: 3.0% vs 5.0% Hyperkalaemia: 8.0% vs 5.0% Nasopharyngitis: 33.0% vs 37.0% |
| Vadadustat (vs ESAs) | |||||||
| PRO2TECT [64] (global) | Darbepoetin alfa | 3476 | 3–5 | 52 | 10–11 (USA) 10–12 (non-USA) | Mean Hb change at 24–36 weeks: 0.74 vs 0.66 g/dl RBC transfusion 24–36 weeks: 2.7% vs 2.2% (ESA untreated), 1.6% vs 1.2% (ESA treated) ESA rescue 24–36 weeks% vs 12.8% (ESA untreated), 5.0% vs 13.4% (ESA treated) | MACE: 22.0% vs 19.9% [HR 1.17 (95% CI 1.01–1.36)] MACE+: 25.9% vs 24.5% [HR 1.11 (95% CI 0.97–1.27)] Hypertension: 17.7% vs 22.1% (ESA untreated), 14.4% vs 14.8% (ESA treated) Hyperkalaemia: 12.3% vs 15.6% (ESA untreated), 9.4% vs 9.9% (ESA treated) |
| Nangaku et al. [65] (Japan) | Darbepoetin alfa | 304 | 3–5 | 52 | 11–13 | Mean Hb level at 20–24 weeks: 11.7 vs 11.9 g/dl Patients with target Hb at 52 weeks: 71.4% vs 84.5% (ESA non-users), 79.2% vs 76.6% (ESA users) | Adverse drug reaction (≥1): 13.2% vs 4.6% Hypertension: 1.3% vs 7.2% Nasopharyngitis: 24.5% vs 28.1% |
| Enarodustat (vs ESAs) | |||||||
| SYMPHONY-ND [67] (Japan) | Darbepoetin alfa | 216 | 3–5 | 24 | 10–12 | Mean Hb level at 20–24 weeks: 10.96 vs 10.87 g/dl Patients with target Hb at 24 weeks: 88.6% vs 87.9% | Retinal disorders: 3.7% vs 0.9% Upper respiratory tract infection: 17.8% vs 22.9% Hypertension: 4.7% vs 4.6% |
| Molidustat vs ESAs | |||||||
| MIYABI ND-C [66] (Japan) | Darbepoetin alfa | 162 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.28 vs 11.70 g/dl Mean Hb change at 30–36 weeks: 1.32 vs 1.69 g/dl Patients with target Hb at 30–36 weeks: 68.3% vs 85.0% Mean IV iron use: 2.89 vs 11.22 mg/week | Serious TEAE: 17.1% vs 7.6% MACE: 7.3% vs 0.0% Hyperkalaemia: 12.2% vs 11.4% Nasopharyngitis: 31.7% vs 26.6% |
| MIYABI ND-M [68] (Japan) | Darbepoetin alfa | 164 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.67 vs 11.53 g/dl Mean Hb change at 30–36 weeks: 0.36 vs 0.24 g/dl Patients with target Hb at 30–36 weeks: 72.0% vs 76.8% | Serious TEAE: 32.9% vs 26.8% MACE: 3.7% vs 1.2% Hyperkalaemia: 2.4% vs 8.5% Hypertension: 2.4% vs 6.1% Diabetic retinopathy: 3.7% vs 1.2% |
| Desidustat (vs ESAs) | |||||||
| DREAM-ND [69] (India and Sri Lanka) | Darbepoetin alfa | 588 | 3–5 | 24 | 10–12 | Mean Hb change at 16–24 weeks: 1.95 vs 1.83 g/dl Mean Hb level at 16–24 weeks: 10.90 vs 10.77 g/dl Patients with Hb response at 24 weeks: 77.8% vs 68.5% Mean hepcidin change at 24 weeks: −12.0 vs 7.8 ng/ml | Serious TEAE: 8.2% vs 6.1% Hypertension: 1.7% vs 5.8% |
| Study . | Comparator . | Patients, n . | CKD stage . | Treatment period (weeks) . | Target Hb (g/dl) . | Efficacy endpoints . | Safety endpoints . |
|---|---|---|---|---|---|---|---|
| Roxadustat (vs ESAs) | |||||||
| DOLOMITES [60] (Europe) | Darbepoetin alfa | 616 | 3–5 | 104 | 10–12 | Patients with Hb response at 24 weeks: 89.5% vs 78.0% Mean monthly IV iron use at 1–36 weeks: 34.7 vs 69.6 mg Time to first use of IV iron at 1–36 weeks: HR 0.46 (95% CI 0.26–0.78) | MACE: 11.8% vs 14.0% [HR 0.81 (95% CI 0.52–1.25)] MACE+: 16.7% vs 18.1% [HR 0.90 (95% CI 0.61–1.32)] VTE: 2.5% vs 0.7% [HR 3.63 (95% CI 0.76–17.20)] |
| Akizawa et al. [61] (Japan) | Darbepoetin alfa | 334 | 2–5 | 24 | 10–12 | Mean Hb change at 18–24 weeks: 0.15 vs 0.22 g/dl Patients with target Hb at 18–24 weeks: 77.1% vs 85.5% | Hypertension: 2.3% vs 3.8% Hyperkalaemia: 3.8% vs 3.8% Nasopharyngitis: 19.1% vs 26.0% Retinal haemorrhage: 31.4% vs 39.8% |
| Daprodustat (vs ESAs) | |||||||
| ASCEND-ND [62] (Global) | Darbepoetin alfa | 3872 | 3–5 | 52 | 10–11 | Mean Hb change at 28–52 weeks: 0.74 vs 0.66 g/dl Use of rescue therapy: 2.0% vs 3.3% RBC transfusion: 12.8% vs 3.5% | MACE (ITT analysis): 19.5% vs 19.2% [HR 1.03 (95% CI 0.89–1.19)] MACE (on-treatment analysis): 14.1% vs 10.5% [HR 1.40 (95% CI 1.17–1.68)] Cancer-related death or tumour progression or recurrence: 3.7% vs 2.5% [RR 1.47 (95% CI 1.03–2.10)] Oesophageal or gastric erosions: 3.6% vs 2.1% [RR 1.70 (95% CI 1.16–2.49)] |
| Nangaku et al. [63] (Japan) | Epoetin beta pegol | 299 | 3–5 | 52 | 11–13 | Mean Hb level at 40–52 weeks (ITT): 12.0 vs 11.9 g/dl Patients with target Hb at 40–52 weeks: 92% vs 92% [OR 1.01 (95% CI 0.33–3.04)] | Hypertension: 3.0% vs 5.0% Hyperkalaemia: 8.0% vs 5.0% Nasopharyngitis: 33.0% vs 37.0% |
| Vadadustat (vs ESAs) | |||||||
| PRO2TECT [64] (global) | Darbepoetin alfa | 3476 | 3–5 | 52 | 10–11 (USA) 10–12 (non-USA) | Mean Hb change at 24–36 weeks: 0.74 vs 0.66 g/dl RBC transfusion 24–36 weeks: 2.7% vs 2.2% (ESA untreated), 1.6% vs 1.2% (ESA treated) ESA rescue 24–36 weeks% vs 12.8% (ESA untreated), 5.0% vs 13.4% (ESA treated) | MACE: 22.0% vs 19.9% [HR 1.17 (95% CI 1.01–1.36)] MACE+: 25.9% vs 24.5% [HR 1.11 (95% CI 0.97–1.27)] Hypertension: 17.7% vs 22.1% (ESA untreated), 14.4% vs 14.8% (ESA treated) Hyperkalaemia: 12.3% vs 15.6% (ESA untreated), 9.4% vs 9.9% (ESA treated) |
| Nangaku et al. [65] (Japan) | Darbepoetin alfa | 304 | 3–5 | 52 | 11–13 | Mean Hb level at 20–24 weeks: 11.7 vs 11.9 g/dl Patients with target Hb at 52 weeks: 71.4% vs 84.5% (ESA non-users), 79.2% vs 76.6% (ESA users) | Adverse drug reaction (≥1): 13.2% vs 4.6% Hypertension: 1.3% vs 7.2% Nasopharyngitis: 24.5% vs 28.1% |
| Enarodustat (vs ESAs) | |||||||
| SYMPHONY-ND [67] (Japan) | Darbepoetin alfa | 216 | 3–5 | 24 | 10–12 | Mean Hb level at 20–24 weeks: 10.96 vs 10.87 g/dl Patients with target Hb at 24 weeks: 88.6% vs 87.9% | Retinal disorders: 3.7% vs 0.9% Upper respiratory tract infection: 17.8% vs 22.9% Hypertension: 4.7% vs 4.6% |
| Molidustat vs ESAs | |||||||
| MIYABI ND-C [66] (Japan) | Darbepoetin alfa | 162 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.28 vs 11.70 g/dl Mean Hb change at 30–36 weeks: 1.32 vs 1.69 g/dl Patients with target Hb at 30–36 weeks: 68.3% vs 85.0% Mean IV iron use: 2.89 vs 11.22 mg/week | Serious TEAE: 17.1% vs 7.6% MACE: 7.3% vs 0.0% Hyperkalaemia: 12.2% vs 11.4% Nasopharyngitis: 31.7% vs 26.6% |
| MIYABI ND-M [68] (Japan) | Darbepoetin alfa | 164 | 3–5 | 52 | 11–13 | Mean Hb level at 30–36 weeks: 11.67 vs 11.53 g/dl Mean Hb change at 30–36 weeks: 0.36 vs 0.24 g/dl Patients with target Hb at 30–36 weeks: 72.0% vs 76.8% | Serious TEAE: 32.9% vs 26.8% MACE: 3.7% vs 1.2% Hyperkalaemia: 2.4% vs 8.5% Hypertension: 2.4% vs 6.1% Diabetic retinopathy: 3.7% vs 1.2% |
| Desidustat (vs ESAs) | |||||||
| DREAM-ND [69] (India and Sri Lanka) | Darbepoetin alfa | 588 | 3–5 | 24 | 10–12 | Mean Hb change at 16–24 weeks: 1.95 vs 1.83 g/dl Mean Hb level at 16–24 weeks: 10.90 vs 10.77 g/dl Patients with Hb response at 24 weeks: 77.8% vs 68.5% Mean hepcidin change at 24 weeks: −12.0 vs 7.8 ng/ml | Serious TEAE: 8.2% vs 6.1% Hypertension: 1.7% vs 5.8% |
Table 2 outlines details of phase 3 comparator trials with ESA therapy, including two roxadustat (one from Europe [60] and one from Japan [61]), two daprodustat (one global [62] and one from Japan [63]), two vadadustat (one global [64] and one from Japan [65]), two molidustat (Japan [66, 68]), one enarodustat (Japan [67]) and one desidustat (South Asia [69]).
Hb: haemoglobin; ITT: intention to treat; OR: odds ratio; MACE: major adverse cardiac event (composite of death, non-fatal MI and/or stroke); MACE+: expanded major adverse cardiac event (MACE plus hospitalization for either heart failure or unstable angina or MACE plus hospitalization for either HF or a thromboembolic event); TEAE: treatment emergent adverse event; vs: versus.
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