Phase 3 Studies of Roxadustat: PYRENEES and ALPS

During a poster session at Kidney
Week 2019, researchers, led by Ciro Esposito, MD, PhD, MFAS, presented
results of two phase 3 European studies of roxadustat, an oral
hypoxia-inducible factor prolyl hydroxylase inhibitor in late-stage development
for the treatment of anemia in patients with chronic kidney disease (CKD). The
poster was titled Two Phase 3, Multicenter, Randomized Studies of
Intermittent Oral Roxadustat in Anemic CKD Patients on (PYRENEES) and Not on
(ALPS) Dialysis.

The open-label PYRENEES study
enrolled 836 stable hemodialysis or peritoneal dialysis-dependent CKD patients
with anemia with hemoglobin 9.5 to 12 g/dL treated with erythropoiesis-stimulating
agents (ESAs). Patients were randomized 1:1 to oral roxadustat or ESAs for 52
to 104 weeks. In the double-blind ALPS study, non–dialysis-dependent CKD
patients with anemia with hemoglobin ≤10 g/L not treated with ESAs were
randomized 2:1 to oral roxadustat or placebo for 52 to 104 weeks.

Primary end points were change from
baseline of average levels of hemoglobin at weeks 28 to 52. Secondary end
points included change of average low-density lipoprotein cholesterol (LDL) at
weeks 12 to 28 from baseline, and time to use of rescue therapy (PYRENEES:
transfusion, ESA, intravenous [IV] iron and ALPS: mean monthly IV iron use
through week 36). The researchers also examined the occurrence of adverse
events.

The ALPS study included 594 patients:
391 were randomized to roxadustat and 203 were randomized to placebo. At weeks
28 to 52, the mean change of average hemoglobin from baseline was 1.988 for
patients in the roxadustat group and 0.406 for those in the placebo group (P<.001).
The least squares mean difference in LDL was  -0.701 (95% confidence interval [CI], -0.83 to -0.57; P<.001) mmol/L in the
roxadustat group versus placebo. Roxadustat was superior to placebo in time to
use of rescue therapy (hazard ratio, 0.238; 95% CI, 0.17-0.33); P<.001).

In the dialysis-dependent patient
study (PYRENEES), the mean change of average hemoglobin levels at weeks 28 to
52 from baseline was 0.396 for the roxadustat group and 0.183 for the ESA group
(P<.001). The least squares mean difference in LDL in the roxadustat
group was -0.377 (95% CI, -0.451 to -0.304; P<.001) mmol/L
versus the ESA group. Roxadustat was superior to ESA in mean monthly IV iron
use (least square mean difference, ­31.9 (95% CI, -41.4 to -22.4; P<.001).

In the ALPS study, adverse events
included end-stage renal disease, hypertension, peripheral edema, and decreased
glomerular filtration rate in both groups. In the PYRENEES study, common adverse
events were hypertension, arteriovenous fistula thrombosis, headache, and
diarrhea.

In conclusion, the researchers said,
“Roxadustat was effective in achieving and maintaining hemoglobin levels
compared with placebo and ESA in non–dialysis-dependent and dialysis-dependent
CKD patients.”

Source: Esposito C, Csiky B,
Tataradze A, Reusch M, Han C, Sulowicz W. Two phase 3, multicenter, randomized
studies of intermittent oral roxadustat in anemic CKD patients on (PYRENEES)
and Not on (ALPS) dialysis. Abstract of a poster presented at the American
Society of Nephrology Kidney Week 2019 (Abstract SA-PO225), November 9, 2019,
Washington, DC.