ARANESP® (darbepoetin alfa) Non-Dialysis HCP Information

IN A RETROSPECTIVE COHORT STUDY OF US EHR DATA

FOR PATIENTS WITH CKD NOT ON DIALYSIS WHO HAVE Hb < 10 g/dL*

In a retrospective observational cohort study of EHR data from a large US healthcare system

Overall, 23% of patients had Hb < 10 g/dL, increasing with each stage to as high as 63% in stage 53,*

Proportion of patients with anemia stratified by population and CKD-NOD stages3

19.3% for stage 3a-b, 42% for stage 4, 63.2% for stage 5

Hb < 10 g/dL
(n = 11,673)

*50,701 adults with stage 3a to 5 CKD not on dialysis.

US EHR data demonstrates

Over 50% of patients with CKD-NOD and Hb < 10 g/dL did not receive any treatment1,*

52.2 percent of patients withouth treatment compared to 48.7 percent that were treated

*14,922 adults with eGFR results > 10 and < 60 mL/min/1.73 m2; average follow-up was 1.96 years; anemia defined as Hb ≤ 10 g/dL.

†IV iron, epoetin alfa, darbepoetin alfa, polyethylene glycol-epoetin beta, or RBC transfusion.

And of those treated, more than half received RBC transfusion as their first anemia treatment1,‡

51.5 percent RBC transfucion, 38.4 percent IV iron, 5.3 percent DPO, and 4.8 percent EPO

Patients treated (n = 7140)

‡Of the 14,922 adults with eGFR results > 10 and < 60 mL/min/1.73 m2, 7140 were treated; average follow-up was 1.96 years; anemia defined as Hb ≤ 10 g/dL.

NOD = not on dialysis; DPO = darbepoetin alfa; EPO = epoetin alfa.

CKDopps revealed low ESA prescribing in the United States

In a multi-country analysis, nephrologists in the United States prescribed ESAs to fewer patients with CKD-NOD and Hb < 10 g/dL.4,*

28% United States, 57% Germany, 52% France, 39% Brazil
28% United States, 57% Germany, 52% France, 39% Brazil

*N = 6766 patients with stage 3a to 5 CKD (not on dialysis) who were sequentially or randomly selected from national samples of nephrology clinics in Brazil, France, Germany, and the United States as part of the CKDopps international prospective cohort study of non-dialysis patients (data from January 1, 2013 until April 13, 2018, which included patients entering CKDopps at different time points over a 5.3 year period); anemia defined as Hb < 10 g/dL.

CKDopps = Chronic Kidney Disease Outcomes and Practice Patterns Study.

Potential impact of RBC transfusions2

ALLOSENSITIZATION

TRANSFUSION REACTIONS

VOLUME OVERLOAD

IRON OVERLOAD

HYPERKALEMIA

TRANSMISSION OF INFECTIONS

The KDIGO® Clinical Practice Guideline for Anemia in Chronic Kidney Disease (2012) recommends avoiding, when possible, red cell transfusions to minimize the general risks related to their use.2

KDIGO® is a registered trademark of the National Kidney Foundation, Inc.


Image of ARANESP® syringe

ARANESP® can be used to reduce the need for RBC transfusion in your CKD-NOD patients with Hb < 10 g/dL.5

Important Dosing Information for ARANESP®

For adult patients with CKD not on dialysis:

  • Consider initiating ARANESP® treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply:
    • The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and,
    • Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.
  • If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of ARANESP®, and use the lowest dose of ARANESP® sufficient to reduce the need for RBC transfusions.
  • The recommended starting dose is 0.45 mcg/kg body weight intravenously or subcutaneously given once at four week intervals as appropriate.

Important Safety Information for ARANESP®

  • In controlled trials, patients with chronic kidney disease experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ARANESP® dose, or dosing strategy that does not increase these risks.
  • Use the lowest ARANESP® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

In an analysis of DOPPS® data

The majority of patients started with Hb < 10 g/dL at hemodialysis initiation6,*

53 percent of patients had anemia in the first month after hemodialysis intiation

Appropriate anemia management in the period before and during hemodialysis transition is important.6

*N = 4604 eligible patients from 21 countries in DOPPS® phases 4-5 (2009-2011) after 4 months on hemodialysis; anemia defined as Hb < 10 g/dL.

DOPPS® = Dialysis Outcomes and Practice Patterns Study.

DOPPS® is a registered trademark of Arbor Research Collaborative for Health.

Anemia at initiation was associated with increased mortality, even if it was corrected within 4 months6,*

Compared with Hb ≥ 11.0 g/dL the start of hemodialysis:

mortality was two times higher for HB less than 8g/dl
mortality was between eighteen and thirty-five percent higher for HB between 8 and 10.9 g/dl

*N = 4604 hemodialysis patients from 21 countries in DOPPS phases 4-5 (2009-2011); anemia defined as Hb < 10 g/dL.

In another analysis of DOPPS data, almost 50% of patients received RBC transfusions during the early hemodialysis period7,*

United states hemodialysis patient statistics. 47.3 percent vintage for less than 120 days and 20.1 percent vintage for greater than, or equal to, 120 days

*N=22,643 hemodialysis patients from 20 countries in DOPPS phases 5-7 (2012-2022).

ARANESP® maintained Hb levels with monthly dosing in patients with CKD-NOD7,*

Hb levels maintained over time with monthly dosing

Median Hb concentrations during the treatment period

a chart showing the tritation and fixed dose over a 97 week period
9.9% g/dL with titration, 9.4% g/dL with fixed dose

ARANESP® achieved median Hb concentrations of 9.9 g/dL in patients who received a titrated dose and 9.4 g/dL in patients who received a fixed dose.

*A double-blind, parallel-group phase 3 trial involving 756 adults with stage 3 to 5 CKD and anemia (Hb < 10.0 g/dL) randomized to receive ARANESP® given as a fixed dose (N = 379) versus administered according to a hemoglobin-based, titration-dose algorithm (N = 377), for up to 2 years. In the hemoglobin-based, titration-dose group, ARANESP® doses were titrated to maintain Hb ≥ 10.0 g/dL, with dose reduction if Hb exceeded 10.5 g/dL or if the Hb rise exceeded 1.0 g/dL over 4 weeks. In the fixed dose group, patients received a fixed dose of ARANESP® (0.45 mg/kg). All patients received ARANESP® as a subcutaneous injection once every 4 weeks. Patients received transfusions as deemed necessary by the treating physician.

ARANESP® dosing options give you the opportunity to control administration and provide individualized anemia management5

Dosing information for adult patients with anemia due to CKD NOT ON DIALYSIS*

*Refer to ARANESP® full Prescribing Information for additional detail on dosing in patients with CKD, including those on dialysis and pediatric patients (less than 18 years).

INITIATION

Consider initiating ARANESP® treatment only when the Hb level is < 10 g/dL and the following considerations apply:

  • The rate of Hb decline indicates the likelihood of requiring a RBC transfusion, and
  • Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal

Q4W recommended starting dose: 0.45 mcg/kg body weight as an IV or SC injection once at 4-week intervals as appropriate.

MONITORING

Following initiation of therapy and after each dose adjustment, monitor Hb at least weekly until the Hb is stable and sufficient to minimize the need for RBC transfusion.

  • Thereafter, Hb should be monitored at least monthly, provided that Hb levels remain stable

DOSE ADJUSTMENTS

When adjusting therapy, consider Hb rate of rise, rate of decline, ESA responsiveness, and Hb variability:

  • A single Hb excursion may not require a dosing change
  • Do not increase the dose more frequently than once every 4 weeks
  • Decreases in dose can occur more frequently
  • Avoid frequent dose adjustments

REDUCE OR INTERRUPT DOSE

If Hb rises rapidly (eg, more than 1 g/dL in any 2-week period), reduce the dose by 25% or more, as needed, to reduce rapid responses.

If the Hb level exceeds 10 g/dL, reduce or interrupt the dose of ARANESP®, and use the lowest dose of ARANESP® sufficient to reduce the need for RBC transfusions.

INCREASE DOSE

If the Hb has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25% when appropriate.

ARANESP® for anemia due to CKD

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a Hb level of greater than 11 g/dL
  • No trial has identified a Hb target level, ARANESP® dose, or dosing strategy that does not increase these risks
  • Individualize dosing and use the lowest dose of ARANESP® sufficient to reduce the need for RBC transfusions
  • Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events

Considerations

  • Correct or exclude other causes of anemia before initiating ARANESP®
  • Evaluate the iron status in all patients before and during treatment
  • Administer supplemental iron therapy if serum ferritin is < 100 mcg/L or serum transferrin saturation is < 20%
  • The majority of patients with CKD will require supplemental iron during the course of ESA therapy
  • Appropriately control hypertension prior to initiation of and during treatment with ARANESP®
    • Reduce or withhold ARANESP® if blood pressure becomes difficult to control

Patients who do not respond adequately to ARANESP®

  • For patients who do not respond adequately over a 12-week escalation period, increasing the ARANESP® dose further is unlikely to improve response and may increase risks
  • Use the lowest dose that will maintain a Hb level sufficient to reduce the need for RBC transfusions
  • Evaluate other causes of anemia
  • If typical causes of lack or loss of Hb response are excluded, evaluate for pure red cell aplasia (PRCA)
  • Discontinue ARANESP® if responsiveness does not improve

Patients with CKD and an insufficient Hb response to ESA therapy or a rate of Hb rise of > 1 g/dL over 2 weeks may be at an even greater risk for cardiovascular reactions and mortality than other patients.

Q4W = every 4 weeks; SC = subcutaneous.

ARANESP® is available in multiple dose strengths, so you can choose the dose that’s right for your patients

dosing-image-mob

Available as a prefilled syringe.

Extended dosing* with proven hemoglobin control

*Due to the longer serum half-life, ARANESP® should be administered less frequently than epoetin alfa. ARANESP® should be administered once a week (QW) if a patient was receiving epoetin alfa 2 to 3 times weekly.
ARANESP® should be administered once every 2 weeks (Q2W) if a patient was receiving epoetin alfa once per week.

LEARN MORE ABOUT AMGEN ESAs

References:

  1. Ma J, Saleem M, Moore C, et al. Contemporary treatment patterns of clinically meaningful anemia among non-dialysis dependent CKD patients in the US.
    Kidney Week 2023; November 1-5, Philadelphia, PA.
  2. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease.
    Kidney Inter. 2012;(suppl 2):279–335.
  3. Lamerato L, James G, van Haalen H, et al. BMC Nephrology. 2022;23:166.
  4. Wong MMY, Tu C, Li Y, et al. Clin Kidney J. 2020;13:613-624.
  5. ARANESP® (darbepoetin alfa) prescribing information, Amgen.
  6. Karaboyas A, Tu C, Richards A, et al. Red blood cell transfusion rates in the early dialysis period: comparing HD (DOPPS®) and PD (PDOPPS) in an international setting. American Society of Nephrology. 2023; November 2-5, Philadelphia, PA.
  7. Toto R, Petersen J, Berns JS, et al. JASN. 2021. doi: https://doi.org/10.1681/ASN.2020050556

ARANESP® (darbepoetin alfa) Important Safety Information, including Boxed WARNINGS

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE

Chronic Kidney Disease:

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ARANESP® dose, or dosing strategy that does not increase these risks.
  • Use the lowest ARANESP® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

Cancer:

  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
  • To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions.
  • Use ESAs only for anemia from myelosuppressive chemotherapy.
  • ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
  • Discontinue following the completion of a chemotherapy course.
  • ARANESP® is contraindicated in patients with:
    • Uncontrolled hypertension
    • Pure red cell aplasia (PRCA) that begins after treatment with ARANESP® or other erythropoietin protein drugs
    • Serious allergic reactions to ARANESP®
  • Use caution in patients with coexistent cardiovascular disease and stroke.
  • Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.
  • In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
  • Control hypertension prior to initiating and during treatment with ARANESP®.
  • ARANESP® increases the risk of seizures in patients with CKD. Monitor patients closely for new-onset seizures, premonitory symptoms, or change in seizure frequency.
  • For lack or loss of hemoglobin response to ARANESP®, initiate a search for causative factors. If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA.
  • Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with ARANESP®.
    • This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration.
    • PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which ARANESP® is not approved).
    • If severe anemia and low reticulocyte count develop during treatment with ARANESP®, withhold ARANESP® and evaluate patients for neutralizing antibodies to erythropoietin.
    • Permanently discontinue ARANESP® in patients who develop PRCA following treatment with ARANESP®, or other erythropoietin protein drugs. Do not switch patients to other ESAs.
  • Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with ARANESP®. Immediately and permanently discontinue ARANESP® if a serious allergic reaction occurs.
  • Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including ARANESP®) in the postmarketing setting. Discontinue ARANESP® therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected.
  • Adverse reactions (≥ 10%) in ARANESP® clinical studies in patients with CKD were hypertension, dyspnea, peripheral edema, cough, and procedural hypotension.

Please see ARANESP® full Prescribing Information, including Boxed WARNINGS and Medication Guide.

See More

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE Chronic Kidney Disease: • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. • No trial has identified a hemoglobin target level, Aranesp® dose, or dosing strategy that does not increase these risks. • Use the lowest ARANESP® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

ARANESP® (darbepoetin alfa) Important Safety Information, including Boxed WARNINGS

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE

Chronic Kidney Disease:

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ARANESP® dose, or dosing strategy that does not increase these risks.
  • Use the lowest ARANESP® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

Cancer:

  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
  • To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions.
  • Use ESAs only for anemia from myelosuppressive chemotherapy.
  • ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
  • Discontinue following the completion of a chemotherapy course.
  • ARANESP® is contraindicated in patients with:
    • Uncontrolled hypertension
    • Pure red cell aplasia (PRCA) that begins after treatment with ARANESP® or other erythropoietin protein drugs
    • Serious allergic reactions to ARANESP®
  • Use caution in patients with coexistent cardiovascular disease and stroke.
  • Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.
  • In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
  • Control hypertension prior to initiating and during treatment with ARANESP®.
  • ARANESP® increases the risk of seizures in patients with CKD. Monitor patients closely for new-onset seizures, premonitory symptoms, or change in seizure frequency.
  • For lack or loss of hemoglobin response to ARANESP®, initiate a search for causative factors. If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA.
  • Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with ARANESP®.
    • This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration.
    • PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which ARANESP® is not approved).
    • If severe anemia and low reticulocyte count develop during treatment with ARANESP®, withhold ARANESP® and evaluate patients for neutralizing antibodies to erythropoietin.
    • Permanently discontinue ARANESP® in patients who develop PRCA following treatment with ARANESP®, or other erythropoietin protein drugs. Do not switch patients to other ESAs.
  • Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with ARANESP®.Immediately and permanently discontinue ARANESP® if a serious allergic reaction occurs.
  • Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including ARANESP®) in the postmarketing setting. Discontinue ARANESP® therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected.
  • Adverse reactions (≥ 10%) in ARANESP® clinical studies in patients with CKD were hypertension, dyspnea, peripheral edema, cough, and procedural hypotension.

Please see ARANESP® full Prescribing Information, including Boxed WARNINGS and Medication Guide.