Last updated: October 28, 2025
Introduction
Daprodustat, marketed as Evrenza® and developed by GlaxoSmithKline (GSK), is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) designed to treat anemia associated with chronic kidney disease (CKD). This therapeutic approach offers an alternative to erythropoiesis-stimulating agents (ESAs), with the potential for improved safety and patient compliance. As the global CKD burden escalates, understanding the clinical trial developments, market landscape, and future projections for Daprodustat provides crucial insights for stakeholders.
Clinical Trials Update
Regulatory Milestones and Trial Outcomes
Daprodustat's clinical development has spanned over a decade, with extensive Phase 3 trials evaluating its efficacy, safety, and tolerability across diverse CKD populations—both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients.
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Achieving Regulatory Approval:
In 2021, GSK received regulatory approval in Japan for Daprodustat (Evrenza®) for anemia in CKD patients on dialysis, a significant milestone marking its transition into mainstream clinical use in one of Asia’s largest markets [1]. This approval followed robust Phase 3 trials demonstrating non-inferior hemoglobin (Hb) control compared to ESAs with a comparable safety profile.
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Key Clinical Trials:
- ASCEND-D (NDD CKD population): Showed Daprodustat was non-inferior to darbepoetin alfa in maintaining Hb levels with potential benefits in adverse event profiles [2].
- ASCEND-ND (Non-dialysis dependent): Confirmed its efficacy in NDD patients, capturing a broader spectrum of CKD-associated anemia.
- ORIGIN Trial: Focused on safety outcomes, particularly cardiovascular events, as safety concerns have historically hampered earlier HIF-PHI development.
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Safety Profile:
Meta-analyses of Phase 3 data affirm Daprodustat's comparable safety to traditional ESAs, with no significant increase in thromboembolic or cardiovascular risks—a persistent concern with anemia treatments [3]. Ongoing long-term studies aim to clarify potential risks over extended use.
Next-Generation Trials and Post-Approval Studies
GSK continues to expand its research portfolio, including:
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Real-World Evidence (RWE):
Post-market studies in Japan and other countries are analyzing the drug’s effectiveness and safety outside controlled trial settings.
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Additional Indications:
Trials investigating Daprodustat's utility in other anemia-related diseases or settings are ongoing, potentially broadening its therapeutic scope.
Market Analysis
Global Market Landscape
The global anemia therapeutics market, estimated at USD 11.7 billion in 2022 and projected to grow at a CAGR of approximately 7.8% until 2030, is heavily influenced by increased CKD prevalence and innovations in anemia management [4].
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Drivers:
- Rising CKD incidence, driven by diabetes and hypertension.
- Limitations of ESAs: safety concerns such as increased thromboembolic risk.
- Patient preference for oral therapies over injectable ESAs.
- Favorable regulatory environments in key markets like Japan and expanding approval strategies in the U.S. and Europe.
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Competitive Landscape:
- Major players include FibroGen (roxadustat), Akebia (vadadustat), and GSK (Daprodustat).
- Roxadustat currently leads in global approvals, especially in China, with regulatory submissions in the U.S. and Europe pending.
- Daprodustat's tailored approval in Japan offers a foothold in a mature nephrology market, with potential for further expansion.
Market Penetration and Commercial Strategy
Regulatory and Market Access Challenges
- Although promising, regulatory hurdles persist, especially around long-term safety data in Western markets. The EMA and FDA have expressed cautious optimism, emphasizing the need for post-marketing surveillance [5].
Market Projections and Outlook
Growth Trajectory and Adoption Potential
GSK forecasts Daprodustat reaching a peak global sales of USD 1.2 billion within five years of broader approvals, driven by:
- Expanding indications and geographical markets.
- Increasing CKD patient populations.
- Growing preference for oral anemia treatments.
Key Market Opportunities:
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Emerging Markets:
Rapid CKD prevalence and unmet medical needs facilitate adoption in countries like China, India, and Brazil.
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Chronic Disease Management Programs:
Integration into comprehensive CKD management initiatives offers further growth.
Challenges to Market Growth:
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Safety Concerns:
Ongoing surveillance is vital. Any safety signals could hamper adoption or extend approval timelines.
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Competitive Dynamics:
Roxadustat remains a competitive threat, with ongoing developments and regulatory strategies.
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Biotech and Pharmacovigilance:
Enhanced pharmacovigilance frameworks and real-world data collection will influence market confidence and reimbursement policies.
Future Outlook
The market forecast for Daprodustat hinges on continued clinical success, regulatory approvals outside Japan, and real-world safety validation. The drug’s unique oral formulation and promising safety profile position it favorably. However, rapid advancements by competitors and the need for extensive safety data may impact its growth trajectory.
In summary, the evolving landscape of anemia therapeutics, marked by the shift towards oral HIF-PHIs, signals significant upside potential for Daprodustat, provided long-term safety remains uncompromised.
Key Takeaways
- Regulatory Milestone: Daprodustat's approval in Japan represents a significant market entry, with indications expanding globally pending further approvals.
- Clinical Efficacy: Demonstrates non-inferior efficacy to ESAs, with promising safety data from Phase 3 trials.
- Market Growth: Expected to grow at a CAGR of approximately 7.8%, fueled by the increasing CKD patient population.
- Competitive Landscape: Faces competition mainly from roxadustat, but its oral administration and safety profile offer competitive advantages.
- Future Risks & Opportunities: Long-term safety and regulatory acceptance remain critical, alongside potential expansion into novel indications.
Frequently Asked Questions (FAQs)
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What is the primary mechanism of action of Daprodustat?
Daprodustat inhibits hypoxia-inducible factor prolyl hydroxylase, stabilizing HIF and promoting erythropoietin production, thereby increasing red blood cell synthesis.
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In which countries is Daprodustat currently approved?
As of 2023, Daprodustat is approved in Japan for dialysis-dependent CKD patients; broader approvals in other regions are pending regulatory review.
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How does Daprodustat differ from traditional ESAs?
Unlike injectable ESAs, Daprodustat is an oral medication offering simplified administration and potentially improved safety profiles related to cardiovascular risks.
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What safety concerns are associated with Daprodustat?
Similar to other HIF-PHIs, safety concerns include cardiovascular events and tumor risks, but current trials indicate comparable safety to ESAs, with ongoing vigilance.
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What is the outlook for Daprodustat’s market growth?
With expanding approvals, increasing CKD prevalence, and oral administration benefits, Daprodustat is poised for significant market penetration within the coming decade.
References
- GSK. GSK’s Daprodustat receives Japanese approval for dialysis-related anemia treatment. (2021).
- ClinicalTrials.gov. ASCEND-D and ASCEND-ND Trials Data.
- Journal of Nephrology & Therapeutics. Safety profiles and meta-analyses of HIF-PHIs.
- Grand View Research. Anemia therapeutics market report, 2022.
- European Medicines Agency & FDA advisories on HIF-PHI safety monitoring.
