Will HIF-PHIs Provide Fresh Oxygen to Fire Up the Renal Anemia Market?
The renal anemia market does not have a wide variety of drug classes available for improving and maintaining patients’ hemoglobin (Hb) levels. However, the therapeutic classes used to treat renal anemia, including iron supplements and erythropoiesis-stimulating agents (ESAs), are well established, despite safety concerns, particularly for the ESAs. Safety concerns such as an increased rate of cardiovascular (CV) events surround ESAs. This concern led to the imposition of black box label warnings, as well as restrictions in use by physicians. Intravenous (IV) irons are also associated with safety concerns such as liver toxicity, iron overload, anaphylaxis, and hypotension.
In addition to safety concerns, experts frequently lament the need for more convenient and cost-effective therapies. IV irons and ESAs are given to patients intravenously or subcutaneously, and these are not ideal options for patients with chronic kidney disease who do not require dialysis (CKD-ND patients). There is also a tough reimbursement environment for renal anemia drugs due to the high price of such agents, particularly the ESAs. Payer restrictions, such as prior authorization (PA), present a challenge to prescribers of renal anemia therapies. However, PA requirements typically decrease as patients progress from CKD-ND to dialysis. Cost controls in dialysis centers also raise uncertainty for current agents. Physicians frequently report pressure from their dialysis chains to use less ESA, to use more iron at the expense of ESAs, and to use lower ESA doses. The high prevalence of renal anemia in chronic kidney disease (CKD) patients means that access to ESAs will continue to be restricted because of the impact on healthcare budgets.
Thought leaders also cite the need for therapies with improved efficacy to treat renal anemia, particularly in patients considered to be ESA hyporesponders (approximately 10% of the dialysis population); ESA hyporesponders do not achieve desired Hb levels despite higher-than-usual doses of ESAs. Efficacy is a key factor impacting the prescribing of renal anemia agents. Demonstrating efficacy benefits, such as increased Hb levels from baseline and greater efficacy in the time required to achieve target Hb levels without the risk of CV events versus established renal anemia therapies such as ESAs, is desired in all patient populations.
The majority of agents in the late-stage renal anemia pipeline are hypoxia-inducible factor, prolyl hydroxylase inhibitors (HIF-PHIs), including FibroGen/Astellas/Astra Zeneca’s roxadustat, Akebia/Otsuka’s vadadustat, and GlaxoSmithKline’s daprodustat. Over the next few years, we expect all three of these agents to launch. Although these drugs are not expected to be significantly more efficacious than ESAs in increasing Hb levels, they are expected to have considerable uptake, particularly in ESA hyporesponders and in the CKD-ND population due to their convenient oral route of administration. Furthermore, the HIF-PH inhibitor class has not posed any serious safety concerns, to date. However, some physicians expressed concerns about the lack of understanding of the mechanism of action or familiarity with HIF-PHIs, which may represent a roadblock for the uptake of these inhibitors. In-depth research into how HIF-PHIs stimulate the body’s natural response to anemia and increase Hb levels, plus confirmation of long-term safety will alleviate some of these concerns.
Overall, experts view these HIF-PHIs with excitement but express concerns regarding long-term safety, as well as future pricing and access. Should the HIF-PHIs’ Phase III trials generate positive outcomes, and not give rise to any major safety concerns, they will likely compete very favorably against ESAs in the renal anemia market. However, HIF-PHIs are expected to be expensive, requiring PA, as ESAs do, leading to relegation to later lines of therapy.
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