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Abstract: PO2113

Roxadustat Lowers Low-Density Lipoprotein Cholesterol in Patients with Anemia of CKD

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

  • Roger, Simon D., Renal Research, Gosford, New South Wales, Australia
  • El-Shahawy, Mohamed A., University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Pollock, Carol A., The University of Sydney, Sydney, New South Wales, Australia
  • Jimenez, Rosa H., FibroGen Inc, San Francisco, California, United States
  • Leong, Robert, FibroGen Inc, San Francisco, California, United States
  • Pola, Maksym, AstraZeneca, Warsaw, Poland
  • Yu, Kin-Hung Peony, FibroGen Inc, San Francisco, California, United States
Background

Roxadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor with positive safety and efficacy results in phase 3 studies in patients with anemia in CKD. The HIF pathway affects cholesterol metabolism; at high altitude, total and low-density lipoprotein cholesterol (LDL-C) decrease in healthy individuals. Roxadustat reduced LDL-C in phase 2 studies. We evaluated the effect of roxadustat on LDL-C in patients with anemia in non–dialysis-dependent (NDD) and dialysis-dependent (DD) CKD.

Methods

Data were pooled from three pivotal phase 3 studies in patients with NDD-CKD and three pivotal phase 3 studies in patients with DD-CKD, including the incident dialysis (ID; on dialysis <4 mo at randomization) population. Mean changes from baseline (CFB) in LDL-C (regardless of statin use) averaged over weeks 12–28 were analyzed using a mixed model of repeated measures and reported least-squares mean (LSM) treatment differences.

Results

In patients with NDD-CKD, there was a 17.2% reduction in LDL-C averaged over Weeks 12–28 in the roxadustat group (n=1994) and a 1.4% increase in the placebo group (n=1430). The LSM treatment difference was statistically significant (p<0.0001). In patients with DD-CKD, there was a 18.5% reduction in the roxadustat group (n=1650) and a 1.7% reduction in the epoetin alfa group (n=1741). The LSM treatment difference was statistically significant (p<0.0001). In patients with ID-DD-CKD, there was a 21.5% reduction in the roxadustat group (n=680) and a 4.6% reduction in the epoetin alfa group (n=691). The LSM treatment difference was statistically significant (p<0.0001).

Conclusion

Treatment with roxadustat vs. placebo or epoetin alfa lowered LDL-C in patients with NDD-CKD and DD-CKD, respectively.

Table: LDL-C Results in NDD-, DD- and ID-DD-CKD Patients (FAS)
 NDD (001, 608, 060)DD (002, 064, 063)ID-DD (002, 064, 063)
 Roxadustat
(n=2368)
Placebo
(n=1865)
Roxadustat
(n=1929)
Epoetin alfa
(n=1928)
Roxadustat
(n=756)
Epoetin alfa
(n=759)
LDL-C averaged over Weeks 12–28
n1994143016501741680691
Mean (SD), mg/dL81.8 (36.2)97.6 (43.8)76.7 (33.0)91.8 (38.5)82.7 (34.0)100.8 (37.6)
LDL-C CFB*
n1994143016501741680691
Mean (SD), mg/dL−17.1 (32.9)1.3 (32.2)−17.3 (27.7)–1.6 (26.1)−22.6 (29.9)−4.8 (27.9)
ANCOVA†
LSM difference (SEM)−19.8 (1.2)–15.8 (0.9)−17.5 (2.4)
(95% CI)(−22.16, −17.51)(–17.54, –14.06)(−22.22, −12.78)
P-value<0.0001<0.0001<0.0001
*Baseline is defined as the last available value prior to the first dose of study treatment.
†Treatment comparison was made using an ANCOVA model with baseline Hb, baseline eGFR, baseline LDL-C as covariates, and study, treatment, study-by-treatment interaction, history of cardiovascular/cerebrovascular/ thromboembolic diseases (Yes vs. No) and region (US, Europe, Other) as fixed effects.
ANCOVA, analysis of covariance; CI, confidence interval; CFB, change from baseline; FAS, full analysis set; LDL-C, low-density lipoprotein cholesterol; LSM, least-squares mean; NDD, non-dialysis dependent; ID, incident dialysis; DD, dialysis dependent; SD, standard deviation; SEM, standard error of the mean.

Funding

  • Commercial Support