1 INDICATIONS AND USAGE JESDUVROQ is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months.

Limitations of Use JESDUVROQ has not been shown to improve quality of life, fatigue, or patient well-being.

JESDUVROQ is not indicated for use: • As a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

• For treatment of anemia of chronic kidney disease in patients who are not on dialysis.

JESDUVROQ is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor indicated for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least four months.

( 1 ) Limitations of Use Not shown to improve quality of life, fatigue, or patient well-being.

Not indicated for use: • As a substitute for transfusion in patients requiring immediate correction of anemia.

• In patients not on dialysis.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Increased Risk of Death, Myocardial Infarction, Stroke, Venous Thromboembolism, and Thrombosis of Vascular Access [see Boxed Warning, Warnings and Precautions ( 5.1 )] .

• Risk of Hospitalization for Heart Failure [see Warnings and Precautions ( 5.2 )] .

• Hypertension [see Warnings and Precautions ( 5.3 )] .

• Gastrointestinal Erosion [see Warnings and Precautions ( 5.4 )] .

Most common adverse reactions (incidence ≥10%) are hypertension, thrombotic vascular events, and abdominal pain.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of JESDUVROQ was evaluated in adults with dialysis-dependent chronic kidney disease with anemia in the ASCEND-D trial based on an on-study analysis (on and off treatment) [see Clinical Studies ( 14.1 )] .

Patients were randomized to JESDUVROQ or rhEPO (epoetin alfa for patients on hemodialysis; darbepoetin alfa for patients on peritoneal dialysis).

Of the 2,964 patients randomized in the trial, 1,487 were randomized to JESDUVROQ, 1,316 (88.5%) of whom were on hemodialysis and 171 (11.5%) of whom were on peritoneal dialysis.

The median extent of exposure to JESDUVROQ and rhEPO was similar.

In the JESDUVROQ treatment arm, 65% of the participants were exposed to at least 18 months of JESDUVROQ and 29% of participants received JESDUVROQ for at least 2.5 years.

JESDUVROQ was non-inferior to rhEPO on the time to first occurrence of major adverse cardiovascular events (MACE) in adults with anemia due to CKD who were on dialysis [see Clinical Studies ( 14.1 )] .

Permanent treatment discontinuation due to an adverse reaction was reported in 19% of patients treated with JESDUVROQ and 18% of patients treated with rhEPO.

No specific adverse reaction resulted in permanent treatment discontinuation in >1% of patients treated with JESDUVROQ.

The most common adverse reactions (≥10% of JESDUVROQ-treated patients) were hypertension, thrombotic vascular events, and abdominal pain.

Table 4 lists the most common adverse reactions (reported in ≥5% of patients treated with JESDUVROQ).

Table 4: Adverse Reactions Reported in ≥5% of Patients Treated with JESDUVROQ in the ASCEND-D Trial Adverse Reaction JESDUVROQ (n = 1,482) % rhEPO (n = 1,474) % Hypertension 24 24 Abdominal pain a 11 8 Dizziness 7 6 Hypersensitivity b 7 7 rhEPO = Recombinant human erythropoietin.

a Includes unspecified abdominal pain, upper abdominal pain, abdominal discomfort.

b Includes rash, urticaria and dermatitis.

Thrombotic Vascular Events Adjudicated thrombotic vascular events (fatal and non-fatal) were observed in 9.8 per 100 PY of patients receiving JESDUVROQ and in 11.7 per 100 PY of patients receiving rhEPO (see Table 5 ).

Table 5: Adjudicated Thrombotic Vascular Events (Fatal and Non-Fatal) in the ASCENDD Trial a Event JESDUVROQ (n = 1,482) rhEPO (n = 1,474) Rate per 100 PY Rate per 100 PY Vascular access thrombosis 5.0 6.3 Myocardial infarction 3.4 4.1 Stroke 1.2 1.5 Deep vein thrombosis 0.7 0.6 Pulmonary embolism 0.3 0.4 PY = Person Years; rhEPO = Recombinant human erythropoietin.

a These data are not an adequate basis for comparison of rates between the study drug and the active control.