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Abstract: FR-OR66

ASCEND Program: Efficacy and Safety from ASCEND-D and -ND and Overall MACE Finding

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • Carroll, Kevin, KJC Statistics Limited, Stockport, United Kingdom
  • Perkovic, Vlado, UNSW Sydney, Newtown, New South Wales, Australia
  • Solomon, Scott D., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jha, Vivekanand, The George Institute for Global Health India, New Delhi, Delhi, India
  • Johansen, Kirsten L., Hennepin Healthcare, Minneapolis, Minnesota, United States
  • Lopes, Renato D., Duke University, Durham, North Carolina, United States
  • Macdougall, Iain C., King's College Hospital, London, London, United Kingdom
  • Obrador, Gregorio T., Universidad Panamericana, Ciudad de Mexico, Ciudad de México, Mexico
  • Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
  • Wanner, Christoph, University Hospital, Wuerzburg, Germany
  • Wheeler, David C., University College London, London, London, United Kingdom
  • Wiecek, Andrzej, Medical University of Silesia, Katowice, Poland
  • Blackorby, Allison, GlaxoSmithKline, Durham, North Carolina, United States
  • Cizman, Borut, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Cobitz, Alexander Ralph, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Davies, Rich, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Dimino, Tara L., GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Dole, Jo Forsythe, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Kler, Lata, GlaxoSmithKline, Middlesex, United Kingdom
  • Meadowcroft, Amy M., GlaxoSmithKilne, Raleigh, North Carolina, United States
  • Taft, Lin, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Zhu, Xinyi, GlaxoSmithKline, Stevenage, United Kingdom
  • McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom

Group or Team Name

  • On behalf of the ASCEND-D authors
Background

The Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis via a novel prolyl hydroxylase inhibitor Daprodustat (ASCEND) phase 3 program investigated efficacy and safety of daprodustat.

Methods

The program included 2 event-driven, cardiovascular outcomes trials (CVOTs) in non-dialysis (ASCEND-ND) and dialysis (ASCEND-D) patients comparing daprodustat with conventional ESAs. Non-inferiority (NI) co-primary endpoints included mean change in hemoglobin (Hb) between baseline and evaluation period (avg over weeks 28–52; NI margin: -0.75 g/dL) and time to first adjudicated major adverse CV event (MACE; NI margin: 1.25). Principal secondary endpoints, adjusted for multiplicity, included superiority assessments of MACE, MACE + thromboembolic events, MACE + hospitalization for heart failure and average monthly intravenous iron dose up to week 52 in ASCEND-D and time to progression of CKD in ASCEND-ND. Three smaller trials also reported adjudicated MACE but were not designed for formal MACE evaluation.

Results

8169 patients were randomized across the 5 trials, with ~14,200 person-years (PY) of follow-up in CVOTs. The co-primary NI Hb objective was met in both CVOTs (adjusted mean treatment difference [95%CI]: ASCEND-D 0.18 [0.12-0.24] g/dL, ASCEND-ND 0.08 [0.03-0.13] g/dL). The co-primary NI MACE endpoint was also met (hazard ratio [95%CI]: ASCEND-D 0.93 [0.81-1.07], ASCEND-ND 1.03 [0.89-1.19]). No principal secondary endpoints met superiority. CVOT rates of treatment emergent adverse events were similar between daprodustat and ESA groups. Figure shows program-level first adjudicated MACE rates per 100 PY (intent-to-treat); MACE rates for ASCEND-NHQ (N=614) were 4.9% for daprodustat and 6.2% for placebo).

Conclusion

CVOTs demonstrated daprodustat was non-inferior to ESA for Hb efficacy and MACE and was well-tolerated. CV safety was generally consistent across treatment groups in the other studies.