Daprodustat
Duvroq
Daprodustat belongs to a novel class of oral treatments for CKD-related anemia. Already available for CKD-related anemia in Japan, its uptake has been impressive. In other markets, upon approval, it is expected to differentiate itself from entrenched, injectable erythropoiesis-stimulating agents (ESAs) by its safety profile, efficacy and oral administration. As such, it will help fill the gap in safe treatments for this growing patient population.
About Daprodustat
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GlaxoSmithKline plc.
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Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
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Oral administration to treat CKD-related anemia, regardless of dialysis status
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~67 million cases of CKD in the G7 markets in 2021
Why is it a drug to watch?
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The approval of high-dose aflibercept (8 mg; EYLEA HD) by the U.S. Food and Drug Administration (FDA) was based on positive results from the pivotal phase 3 PULSAR (wet AMD) and PHOTON (DME) studies. Both studies met their primary endpoints with EYLEA HD (administered every 12 or 16 weeks after three initial monthly doses), demonstrating non-inferiority to EYLEA (dosed every 8 weeks following the loading phase) in visual acuity gains from baseline at week 48 while providing a similar safety profile.
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The real benefit is expected from the need for fewer injections to reach equivalent visual acuity gains and anatomical features as EYLEA without compromising safety, therefore reducing the treatment burden for patients and healthcare providers. Compelling trial results through two years reinforce the ability of EYLEA HD to prolong treatment intervals of at least 12 weeks to a meaningful proportion of patients:
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Approved by the Ministry of Health, Labour and Welfare (MHLW) in Japan and under review by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), daprodustat is an HIF-PHI developed to treat anemia associated with CKD, which has a high incidence rate and few effective, safe treatment options. The New Drug Application (NDA) submitted to the U.S. FDA was supported by results from the phase 3 ASCEND program, which included five studies investigating daprodustat across the spectrum of CKD:
- ASCEND-ND (non-dialysis), ASCEND-D (dialysis), ASCEND-ID (incident dialysis) and ASCEND-TD (dialysis): daprodustat versus the standard of care, ESAs, resulting in hemoglobin within target levels and non-inferiority of major adverse cardiovascular events (MACE)
- ASCEND-NHQ: daprodustat versus placebo, resulting in increased hemoglobin and similar adverse events with daprodustat In 2018, GSK plc and Kyowa Hakko Kirin entered into a strategic collaboration agreement for Kyowa Hakko Kirin to commercialize daprodustat in Japan.
Review and approval status
June 2020
Marketing authorization: MHLW
March 2022
Marketing authorization application (MAA) validated: European Medicines Agency (EMA)
August 2023
sNDA/sBLA accepted: Mainland China NMPA
April 2022
NDA accepted: U.S. FDA
February 1, 2023
PDUFA date
Actual and expected launch:
- 2020: Japan
- 2023: United States and Europe
Patents estimated to expire beginning in 2027
How will daprodustat impact the market for CKD-related anemia?
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In the face of competition, uptake of daprodustat might be fostered by its:
- oral formulation (versus intravenous)
- effective hemoglobin-raising efficacy for patients that have failed ESA therapy
- reduction in the need for iron supplementation
- likelihood for competitive pricing in comparison with the market-leading ESA brands
What gaps in treatment does daprodustat fill?
Anemia is a common complication of CKD and worsens as kidney disease progresses. Current treatment involves injectable recombinant ESAs, which have associated serious adverse cardiac reactions and risk of sudden cardiac death in addition to inconsistent responses. Daprodustat could potentially be a game changer for these patients, providing a safer option that significantly improves outcomes regardless of dialysis status.
What hurdles might it need to overcome to reach blockbuster status?
Daprodustat will compete with Aranesp®, MIRCERA® and EPOGEN®/PROCRIT®, which currently dominate market sales, in addition to other well-established therapeutic approaches in CKD such as intravenous iron replacement products and blood transfusions that offer rapid increases in hemoglobin levels. In October, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted in favor of the drug’s use in adult dialysis patients, but not in adult non-dialysis patients.
$0.53B
95%
Drug Timeline & Success Rates
*Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of December 15, 2021
