Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients

Coyne, Daniel W.; Singh, Ajay K.; Lópes, Renato D.; Bailey, Christine K; DiMino, Tara; Huang, Ching‐Wen; Connaire, Jeffrey; Rastogi, Anjay; Kim, Sung-Gyun; Orías, Marcelo; Shah, Sapna; Patel, Vickas V.; Cobitz, Alexander R.; Wanner, Christoph

doi:10.2215/cjn.00550122

Cited by 17 publications

(24 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, the administration frequency used in Phase 3, randomised clinical trials (RCTs) differs for the HIF-PHIs molecules, with roxadustat given three times per week, while the others are administered once a day. Recently, a small trial in DD-CKD patients showed preserved efficacy of daprodustat when given three times weekly during in-centre haemodialysis sessions instead of the original once-daily dosing [32].…”

Section: Mechanism Of Action Of Hif-phismentioning

confidence: 99%

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Locatelli

Minutolo²,

Nicola³

et al. 2022

Drugs

View full text Add to dashboard Cite

Chronic kidney disease (CKD) affects approximately 10% of the worldwide population; anaemia is a frequent complication. Inadequate erythropoietin production and absolute or functional iron deficiency are the major causes. Accordingly, the current treatment is based on iron and erythropoiesis stimulating agents (ESAs). Available therapy has dramatically improved the management of anaemia and the quality of life. However, safety concerns were raised over ESA use, especially when aiming to reach near-to-normal haemoglobin levels with high doses. Moreover, many patients show hypo-responsiveness to ESA. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors (HIF-PHIs) were developed for the oral treatment of anaemia in CKD to overcome these concerns. They simulate the body's exposure to moderate hypoxia, stimulating the production of endogenous erythropoietin. Some molecules are already approved for clinical use in some countries. Data from clinical trials showed non-inferiority in anaemia correction compared to ESA or superiority for placebo. Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors may also have additional advantages in inflamed patients, improving iron utilisation and mobilisation and decreasing LDL-cholesterol. Overall, non-inferiority was also shown in major cardiovascular events, except for one molecule in the non-dialysis population. This was an unexpected finding, considering the lower erythropoietin levels reached using these drugs due to their peculiar mechanism of action. More data and longer follow-ups are necessary to better clarifying safety issues and further investigate the variety of pathways activated by HIF, which could have either positive or negative effects and could differentiate HIF-PHIs from ESAs.

show abstract

Section: Mechanism Of Action Of Hif-phismentioning

confidence: 99%

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Locatelli

Minutolo²,

Nicola³

et al. 2022

Drugs

View full text Add to dashboard Cite

show abstract

“…Effect of HIF-PHI on blood pressure and CKD progression: pre-clinical studies and early clinical studies showed that HIF-PHIs corrected anemia without increasing blood pressure [ 57 , 64 ]. A recent phase 3 study (ASCEND-TD) showed a similar effect of daprodustat on blood pressure compared with ESA [ 65 ]. There are no published clinical studies that specifically examined the effect of HIF-PHI on CKD progression.…”

Section: Other Potential Effects Of Hif-phismentioning

confidence: 99%

Updates on Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in the Treatment of Renal Anemia

Hao

2022

Kidney Dis

View full text Add to dashboard Cite

Background: Anemia is a common complication of chronic kidney disease. The hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) is a new class of oral drugs for the treatment of renal anemia. Summary: Clinical trials have consistently shown that HIF-PHIs can effectively increase hemoglobin in both the dialysis population and the non-dialysis population. The effects of HIF-PHIs in treating renal anemia include promoting endogenous erythropoietin production and facilitating iron mobilization. Several studies suggest that the erythropoiesis effect of roxadustat is less affected by inflammation. Careful monitoring of thromboembolic events and tumor before and during HIF-PHIs treatment is necessary. Key messages: HIF-PHIs are effective in correcting renal anemia. The long-term safety of HIF-PHIs needs to be further studied.

show abstract

“…Initial literature searches are described in Figure 1. Ultimately, nineteen DD-related eligible studies were included [2,12,16,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. We searched the literature and finally included six agents of HIF-PHIs, including Roxadustat [12,16,[26][27][28][29][30], Daprodustat [31][32][33][34][35], Vadadustat [2,36], Molidustat [37,38,40], Enarodustat [39], and Desidustat [41].…”

Section: Study Selectionmentioning

confidence: 99%

“…Ultimately, nineteen DD-related eligible studies were included [2,12,16,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. We searched the literature and finally included six agents of HIF-PHIs, including Roxadustat [12,16,[26][27][28][29][30], Daprodustat [31][32][33][34][35], Vadadustat [2,36], Molidustat [37,38,40], Enarodustat [39], and Desidustat [41]. One of the studies described two different RCTs of Vadadustat, and both trials compared Vadadustat and Darbepotin, including respectively incident DD CKD trial (369 participants) and prevalent DD CKD trial (3554 participants) [2].…”

Section: Study Selectionmentioning

confidence: 99%

“…We analyzed the risk of cardiovascular events of HIF-PHIs in 17 trials, including 13,492 participants [2,12,16,[26][27][28][30][31][32][33][34][35][36][37][38][39]. No obviously increased RR was indicated in DD patients with Roxadustat (RR: 1.00, 95% CI: 0.88-1.14, p=0.97, I 2 =0%), Enarodustat (RR: 2.97, 95% CI: 0.12-71.80, p=0.50, I 2 =0%), Daprodustat (RR: 0.96, 95% CI: 0.85-1.08, p=0.48, I 2 =0%), Vadadustat (RR: 0.94, 95% CI: 0.83-1.07, p=0.35, I 2 =0%) and Molidustat (RR: 0.82, 95% CI: 0.38-1.73, p=0.60, I 2 =0%) compared with the ESAs.…”

Section: Cardiovascular Eventsmentioning

confidence: 99%

See 1 more Smart Citation

Safety of HIF Prolyl-Hydroxylase Inhibitors for Anemia in Dialysis Patients: A Systematic Review and Network Meta-Analysis

Chen

Niu

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

Aim: We performed a systematic review and network meta-analysis, evaluating the safety and efficacy of Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among dialysis chronic kidney disease (CKD) patients. Methods: Safety was evaluated with any adverse events (AEs), serious adverse events (SAEs), and twelve common events. Efficacy was mainly analyzed with hemoglobin (Hb) response. All reported results were summarized using mean difference (MD) and risk ratio (RR) with 95% confidence interval (CI). Publication bias was assessed through funnel plots. Results: Twenty trials with 14,947 participants were included, comparing six HIF-PHIs with Erythropoiesis-stimulating agents (ESAs). No significant differences were indicated in AEs and SAEs between each HIF-PHI and ESA. The occurrence of gastrointestinal disorder was higher in Enarodustat and Roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52-31.40, p=0.01; RR: 1.30, 95% CI: 1.04-1.61, P=0.02). The occurrence of hypertension was lower in Vadadustat than in ESAs (RR: 0.81, 95% CI: 0.69-0.96, p=0.01). The occurrence of vascular-access complications was higher in Roxadustat (RR: 1.15, 95% CI: 1.04-1.27, p＜0.01) while lower in Daprodustat (RR: 0.78, 95% CI: 0.66-0.92, p＜0.01) than in ESAs. In the risk of the other nine events, including cardiovascular events, no significant differences were observed between HIF-PHIs and ESAs. For efficacy, network meta-analysis showed that the overall performance was similar to ESAs. Conclusion: Although HIF-PHIs did not show significant differences from ESAs in terms of overall AEs and SAEs, statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications were observed between HIF-PHIs, which deserved to be noted in clinical decision-making.

show abstract

Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients

Cited by 17 publications

References 29 publications

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Updates on Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in the Treatment of Renal Anemia

Safety of HIF Prolyl-Hydroxylase Inhibitors for Anemia in Dialysis Patients: A Systematic Review and Network Meta-Analysis

Contact Info

Product

Resources

About