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Abstract: PO0465

Daprodustat Is Noninferior to Darbepoetin Alfa in Treating Anemia in Incident Dialysis Patients

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Author

  • Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States

Group or Team Name

  • for the ASCEND-ID Study Group
Background

Daprodustat (Dapro) is a hypoxia-inducible factor prolyl hydroxylase inhibitor that is being evaluated as an alternative to conventional erythropoiesis stimulating agent (ESA) therapy. Treatment with Dapro in incident dialysis dependent (ID) patients (pts) that are at high risk for co-morbidity and mortality has not been examined previously. This Phase 3 trial evaluated the efficacy and safety of Dapro vs darbepoetin alfa (Darbe) in the ASCEND-ID (NCT03029208) study.

Methods

Pts who started on hemodialysis (HD) or peritoneal dialysis (PD) were randomized to Dapro or Darbe to maintain hemoglobin (Hb) at 10–11 g/dL in an open-label (sponsor-blind) 52-week study. Eligible pts were <3 months from initiation of HD or PD, ESA naïve or of limited ESA exposure, Hb 8–11.0 g/dL, and iron replete.

Primary endpoint tested non-inferiority of Dapro vs Darbe (analysis of covariance) for mean change in Hb between baseline (BL) and Evaluation Period (EP) in weeks 28–52. Secondary endpoint included IV iron use.

Results

312 pts from 14 countries were randomized; of those, 81% started on HD and 31% had an unplanned dialysis start. Overall 99% (155/157) pts on Dapro and 97% (151/155) on Darbe completed the study. Major BL characteristics were balanced, except age (mean 53.7 y vs 55.8 y) and history of heart failure (16% vs 22%) in Dapro vs Darbe, respectively. Hb measurements from EP are shown below.

Mean (SD) Hb in EP was 10.5 (1.0) g/dL and 10.6 (0.9) g/dL (Dapro vs Darbe). There was no significant difference in mean (SE) monthly IV iron use 145 (10.9) mg vs 125 (11.0) mg (Dapro vs Darbe). Rescue treatment was the same in both groups (3%).

While the number of subjects with worsening of hypertension (24% Dapro vs 19% Darbe) was numerically higher, the overall effect of dapro on BP was similar to Darbe. Rates of AEs were similar (76% Dapro vs 72% Darbe).

Conclusion

In a high-risk incident dialysis population, Dapro was non-inferior to Darbe in maintaining Hb in the target range. Dapro was well tolerated and appears to be a safe alternative to Darbe.

Mean Difference in Hb Change from BL in Dapro vs Darbe groups
Hb analysis
Weeks 28–52
PopulationArmn/N (%)Adjusted mean Hb (g/dL)
difference (95% CI)*
Post-randomization
(observed and imputed)
ITTDapro
Darbe
157/157 (100)
155/155 (100)
-0.10 (-0.34, 0.14)
EvaluableITTDapro
Darbe
133/157 (85)
133/155 (86)
-0.20 (-0.43, 0.04)
EvaluablePPDapro
Darbe
77/77 (100)
101/101 (100)
-0.12 (-0.38, 0.14)
*Non-inferiority was declared when the lower boundary of the 95% CI for the treatment difference was greater than the prospectively defined non-inferiority margin of 0.75 g/dL.
ITT, intent-to-treat PP, per-protocol

Funding

  • Commercial Support