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Co-primary Endpoint

Exploratory Endpoints

Study Design

Co-primary Endpoint

Exploratory Endpoints

Study Design

Oral JESDUVROQ (daprodustat) raised and maintained Hb levels within target range, similar to ESA1

Oral JESDUVROQ (daprodustat) raised and maintained Hb levels within target range, similar to ESA1

CO-PRIMARY ENDPOINT (ASCEND-D Trial)

Comparable Hb response to ESA from baseline to Evaluation Period (ITT)1*

  JESDUVROQ
(n=1,487)		 ESA†
(n=1,477)
Primary endpoint: change in Hb‡
Mean baseline Hb, g/dL (SD) 10.4 (1.0) 10.4 (1.0)
Hb change, g/dL (SE)§‖ 0.3 (0.02) 0.1 (0.02)
Mean treatment difference (95% CI)‖ 0.2 (0.1, 0.2)

Noninferiority was achieved because the lower limit of the 95% CI of the treatment difference was greater than the prespecified noninferiority margin of –0.75 g/dL.1

Results were similar in patients receiving either hemodialysis or peritoneal dialysis.1¶

*ITT analyses included observed and imputed values on/off treatment after randomization. 8% of patients had no observed Hb change during Weeks 28-52.
†Patients on hemodialysis received epoetin alfa; patients on peritoneal dialysis received darbepoetin alfa.
‡Adjusted for multiplicity.
§Mean Hb change from baseline to Evaluation Period: Weeks 28-52.
‖Adjusted for baseline covariates.
Not adjusted for multiplicity.

Oral JESDUVROQ has evidence based on a robust clinical trial1

The efficacy and safety of JESDUVROQ were evaluated in adults with Anemia due to Chronic Kidney Disease (CKD) on dialysis for at least 4 months and receiving an ESA at the time of study entry in a randomized, sponsor-blind, active-controlled, global, event-driven clinical trial (N=2,964). Study co-primary endpoints were mean change in Hb from baseline to the Evaluation Period (Weeks 28-52) and time to first adjudicated MACE, using a noninferiority comparison for JESDUVROQ to ESA for both endpoints.1

REVIEW STUDY DESIGN

EXPLORATORY ANALYSIS (ASCEND-D Trial)

Hb level over time (ITT population)2,3

A trial-specific algorithm was used for both treatment groups to achieve and maintain an Hb level in the target range of 10.0 to 11.0 g/dL.2

Hb Levels Over Time graph

Data outside of Evaluation Period are descriptive and are not an adequate basis for comparison between JESDUVROQ and ESA.

*The horizontal lines represent the Hb analysis range (10.0 to 11.5 g/dL), which is an extension of the target range to allow for variability.
†Patients on hemodialysis received epoetin alfa; patients on peritoneal dialysis received darbepoetin alfa.

The effect of JESDUVROQ across select prespecified subgroups2,4

Forest plot by subgroup for Hb efficacy (ITT population)4
JESDUVROQ and ESA Patient subgroup infographic

These prespecified subgroup analyses were not adjusted for multiplicity. No statistical conclusions can be drawn.

*ESA hyporesponsiveness was defined as an ESA Resistance Index (ERI) of at least 2.0 in patients who had previously received epoetin alfa or the previous receipt of the equivalent of at least 450 U/kg of intravenous epoetin alfa per week. The ERI is calculated as the standardized dose of ESA (in U/week) during the 8-week screening period divided by the patient’s baseline estimated dry weight (in kg) and by the Hb level (in g/L) on Day 1.

Patients Mary and James

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EXPLORATORY ANALYSIS (ASCEND-D Trial)

Time to first occurrence of RBC or whole blood transfusion during the on-treatment time period (safety population)3,4

Transfusion data graph

This analysis was not prespecified in the testing hierarchy and no statistical conclusions can be drawn. These data are not an adequate basis for comparison between JESDUVROQ and ESA.

% of patients who received ≥1 RBC or whole blood transfusion from Day 1 to the day after discontinuation of the trial‑specific dosing algorithm was 15.7% for JESDUVROQ and 18.3% for ESAs.2

*Patients on hemodialysis received epoetin alfa; patients on peritoneal dialysis received darbepoetin alfa.

Efficacy and safety of JESDUVROQ were evaluated in a robust clinical trial1

Pivotal cardiovascular outcomes trial1,2
ASCEND/D Dialysis
ASCEND/D Dialysis
Patient Selection Criteria

Key entry criteria1,2:

  • Adults with Anemia of CKD undergoing dialysis for at least 90 days at screening
  • Receiving ESA at the time of study entry

Key exclusion criteria1:

  • Ferritin ≤100 ng/mL and transferrin saturation ≤20% at screening
  • Evidence of nonrenal anemia
  • Cardiovascular abnormalities (including myocardial infarction, acute coronary syndrome, stroke, or transient ischemic attack within 4 weeks of screening, NYHA Class IV heart failure, and uncontrolled hypertension)
  • Liver disease
  • History of malignancy within 2 years of screening
  • Current treatment of cancer and complex kidney cyst

ASCEND-D had co-primary endpoints evaluated for noninferiority vs ESA, including cardiovascular safety1

SEE MACE RESULTS

Review ASCEND-D baseline characteristics

Patient characteristics were well balanced between JESDUVROQ and ESAs at baseline.2

Baseline characteristic* JESDUVROQ
(n=1,487)		 ESA
(n=1,477)
Median age (IQR), years 58 (48-67) 59 (47-68)
Sex, n (%)
Female 636 (42.8) 630 (42.7)
Male 851 (57.2) 847 (57.3)
Race or ethnic group,† n (%)
White 995 (66.9) 982 (66.5)
Black 228 (15.3) 233 (15.8)
Asian 176 (11.8) 181 (12.3)
Dialysis type at randomization, n (%)
HemodialysisHemo-dialysis 1,316 (88.5) 1,308 (88.6)
Peritoneal dialysis 171 (11.5) 169 (11.4)
ESA hyporesponsiveness,‡ n (%)
ESAESA hyporesponsivenesshypo-responsive-ness 183 (12.3) 180 (12.2)
Coexisting condition, n (%)
Cardiovascular disease§Cardio-vascular disease§  666 (44.8) 665 (45.0)
HypertensionHyper-tension 1,366 (91.9) 1,373 (93.0)
Diabetes 615 (41.4) 617 (41.8)
Laboratory values‖
Mean Hb, g/dL 10.35±0.97 10.39±0.98

*Plus/minus values are means ±SD. Data are for the ITT population unless otherwise noted.
†Race or ethnic group was reported by the patients.
‡ESA hyporesponsiveness was defined as an ESA Resistance Index (ERI) of at least 2.0 in patients who had previously received epoetin alfa or the previous receipt of the equivalent of at least 450 U/kg of intravenous epoetin alfa per week. The ERI is calculated as the standardized dose of ESA (in U/week) during the 8-week screening period divided by the patient’s baseline estimated dry weight (in kg) and by the Hb level (in g/L) on Day 1.
§Patients could have more than one type of cardiovascular disease.
‖All baseline laboratory tests were performed by a central laboratory except for Hb, for which central laboratory values were reported if available or a point-of-care HemoCue value if the central laboratory value was missing.

ASCEND-D, Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Dialysis; CI, confidence interval; ESA, erythropoiesis‐stimulating agent; Hb, hemoglobin; IQR, interquartile range; ITT, intent-to-treat; MACE, major adverse cardiovascular event; NYHA, New York Heart Association; RBC, red blood cell; SD, standard deviation; SE, standard error.

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