#3026 Uncovering the potential of HIF-PH inhibitors to treat renal anemia

Abstract

Abstract Background and Aims Hypoxia-inducible factor prolyl hydroxylase enzyme inhibitors (HIF-PHis) are a novel class of agents that were developed for the treatment of renal anemia. The agents work by stabilizing the HIF complex and stimulating endogenous erythropoietin production. This research aims to gauge the potential utilization and impact of HIF-PHis based on the perspectives of nephrologists who are based in the EU5. Method Data were collected via an independent online survey of 204 nephrologists based in the EU5 (UK, Germany, Italy, France, and Spain) in November 2023. Results EU5 nephrologists report that most dialysis and CKD non-dialysis patients with renal anemia who are on ESA therapy have an optimal response to treatment; however, a substantial proportion of patients experience a suboptimal response to treatment and up to 13% of patients across dialysis modalities are classified as ESA hypo-responders. Regardless of their geographic location, EU5 nephrologists position HIF-PHis to offer the most value in the CKD non-dialysis patient setting, with a perceived high level of opportunity (80%) for roxadustat to improve renal anemia outcomes among non-dialysis patients. Not surprisingly, the perceived advantages of an oral agent over an injectable medication for the treatment of renal anemia are more substantial for dialysis patients who are receiving home therapies (peritoneal and home hemodialysis) compared to those receiving in-center hemodialysis treatment. EU5 nephrologists also tend to believe that roxadustat represents a high level (64%) of opportunity to improve renal anemia outcomes in dialysis patients, with similar ratings observed for vadadustat (63%) in the same patient population. Specific to the use of HIF-PH inhibitors in the CKD non-dialysis setting, nephrologists are most concerned about patient compliance (51%), followed by safety compared to ESAs in general and as they relate to cardiovascular events (36%). When considering the use of HIF-PH inhibitors in the dialysis setting, nephrologists express similar concerns compared to the non-dialysis setting, with patient compliance (50%) ranked as the top concern, followed by safety compared to ESAs (38%), and the potential for off target effects (33%). Most EU5 nephrologists agree that HIF-PH inhibitors represent a more physiologic way of treating anemia of CKD compared to ESAs (70%) and many would like gain more clinical experience with the class of medications (63%). Current roxadustat treatment rates in dialysis are slowly increasing across the EU5 region, with slightly higher adoption in peritoneal dialysis patients (10%) compared to in-center hemodialysis patients (8%). Meanwhile, their self-reported uptake of roxadustat in CKD non-dialysis patients is also increasing over time, with the largest increase observed in CKD Stage 4 patients (9%). There is little consensus among EU5 nephrologists regarding their expected time to trial vadadustat once it is available, as nearly the same proportion of prescribers project that they will prescribe the agent to their dialysis patients within three months (36%), six months (23%), and within one year (28%). Conclusion With HIF-PHis having more of a physiologic mechanism of action, oral administration, and a similar safety profile compared to ESAs, broader adoption of the novel agents will potentially help address unmet needs and improve patient outcomes in the treatment of renal anemia for both CKD non-dialysis and dialysis patients.