Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Aranesp is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia due to: Chronic Kidney Disease (CKD) in patients on dialysis and patients not on dialysis ( 1.1 ). The effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy ( 1.2 ). FDA label
Also known as Darbepoetin alfa SC, Darbepoetin alfa-kg, Aranesp®, Novel Erythropoiesis Stimulating Protein (NESP)
darbepoetin alfa · 40 trials · 29 indications
Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 indicates a mild AE, Grade 2 indicates a moderate AE, Grade 3 indicates severe or medically significant but not immediately life-threatening and Grade 4 indicates life-threatening consequences; urgent intervention indicated. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: * fatal * life threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event The investigator assessed whether each adverse events was related to darbepoetin alfa.
The percentage of participants receiving at least 1 RBC transfusion during the evaluation period was recorded for each treatment group. The evaluation period began from the date of randomization, and participants were censored at the last dose of investigational product plus 3 months or end of study, whichever was earlier (on-treatment approach).
The Adjusted Analysis is the primary analysis and includes treatment group and baseline Hb value as covariates. Non-inferiority is concluded if the lower limit of the 95% confidence interval for the mean difference is above -0.5g/dL.
Time to death from any cause or first hospital admission for worsening heart failure (adjudicated by the Clinical Endpoint Committee), whichever occurred first, estimated by Kaplan-Meier method. Participants not experiencing a qualifying event during the study were censored at their last contact time or the study termination date, whichever occurred first.
Time from randomization to the first confirmed composite event. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized.
Time from randomization to first event of all-cause mortality or ESRD. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized.
Target hemoglobin was defined as ≥ 11 g/dL during the treatment period in the absence of a red blood cell (RBC) transfusion on the day of measurement or during the preceding 28 days.
Target hemoglobin was defined as ≥ 11 g/dL during the treatment period in the absence of a red blood cell (RBC) transfusion on the day of measurement or during the preceding 28 days.
| Arm | Type | Description |
|---|---|---|
| Darbepoetin Alfa | EXPERIMENTAL | Participants received darbepoetin alfa for up to 73 weeks or until progression to acute myeloid leukemia (AML), whichever occurred first. |
| Hb-Based Titration Group | ACTIVE_COMPARATOR | Participants received darbepoetin alfa as a subcutaneous (SC) injection once every 4 weeks (Q4W) for up to 96 weeks. The dose of darbepoetin alfa was titrated based on the Hb concentration on the date of the visit, the corresponding Hb rate of rise (ROR), and the previously assigned dose. Doses were reduced if Hb exceeded 10.5 g/dL or Hb ROR exceeded 1.0 g/dL/4W. When darbepoetin alfa therapy was withheld per the dosing algorithm, placebo was administered. The starting dose of darbepoetin alfa was 0.45 micrograms/kilogram (mcg/kg) and the protocol specified doses ranged from 10 to 300 mcg. |
| Fixed Dose Group | EXPERIMENTAL | Participants received darbepoetin alfa as a SC injection Q4W at the same dose as assigned at the time of randomization for the duration of the 96 week treatment period. There was 1 exception to the fixed dose strategy: if the Hb was \> 12.0 g/dL, darbepoetin alfa therapy was withheld and placebo administered. Once the Hb fell to \< 10.0 g/dL, darbepoetin alfa therapy resumed at the same dose. The starting dose of darbepoetin alfa was 0.45 mcg/kg and the protocol specified doses ranged from 10 to 300 mcg. |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks during the double-blind treatment period. From week 25 participants received darbepoetin alfa 500 µg Q3W during the active treatment period for 48 weeks. |
| Q2W | ACTIVE_COMPARATOR | Q2W administration of darbepoetin alfa. |
| QM | ACTIVE_COMPARATOR | QM administration of darbepoetin alfa |
| Single | OTHER | - |
| Roller bottle | ACTIVE_COMPARATOR | - |
| Serum free | EXPERIMENTAL | - |
| Active | ACTIVE_COMPARATOR | - |
| Darbepoetin alfa 6.75 mcg/kg Q4W | EXPERIMENTAL | - |
| Placebo Q4W | PLACEBO_COMPARATOR | - |
| Darbepoetin alfa 500 mcg - Group A | EXPERIMENTAL | - |
| Darbepoetin alfa 2.25 mcg/kg - Group B | ACTIVE_COMPARATOR | - |
| Darbepoetin alfa - Group A | EXPERIMENTAL | - |
| Placebo- Group B | PLACEBO_COMPARATOR | - |
| Group 1 - darbepoetin alfa | EXPERIMENTAL | Darbepoetin alfa 300 mcg QW for the first 4 weeks, followed by Q3W dosing commencing on week 5 for the remainder of the treatment period. |
| Group 2 - Placebo | PLACEBO_COMPARATOR | Placebo QW for the first 4 weeks, followed by Q3W dosing commencing on week 5 for the remainder of the treatment period. |
| rHuEPO | ACTIVE_COMPARATOR | - |
| Darbepoetin alfa 300 μg plus IV Iron | EXPERIMENTAL | Darbepoetin alfa 300 μg subcutaneous injection plus intravenous (IV) iron 400 mg, every three weeks (Q3W), for up to 15 weeks (a total of 5 doses). |
| Darbepoetin alfa 300 μg | EXPERIMENTAL | Darbepoetin alfa 300 μg subcutaneous injection every three weeks (Q3W), for up to 15 weeks (a total of 5 doses). |
| Darbepoetin alfa 500 μg | EXPERIMENTAL | Darbepoetin alfa 500 μg subcutaneous injection every three weeks (Q3W), for up to 15 weeks (a total of 5 doses). |
| Darbepoetin alfa 500 μg plus IV Iron | ACTIVE_COMPARATOR | Darbepoetin alfa 500 μg subcutaneous injection plus intravenous (IV) iron 400 mg, every three weeks (Q3W), for up to 15 weeks (a total of 5 doses). |
| test treatment period | EXPERIMENTAL | - |
| Darbepoetin alfa SC | ACTIVE_COMPARATOR | - |
| Darbepoetin alfa IV | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Darbepoetin Alfa | DRUG | The first dose of darbepoetin alfa was the same as that administered at the last dosing visit of the active treatment period in Study 20090160. Doses could be increased up to a maximum of 500 μg every two weeks (Q2W). |
| Placebo | OTHER | Placebo was presented as single use PFS. Participants received a SC placebo injection in place of darbepoetin alfa therapy when the dose of study drug was withheld per the dosing algorithm for the duration of the treatment period. |
| Darbepoetin alfa - 2.25 mcg/kg | DRUG | Darbepoetin alfa 2.25 mcg/kg QW dosing/ placebo Q3W |
| Darbepoetin alfa - 500mcg | DRUG | Darbepoetin alfa 500mcg Q3W dosing / placebo QW |
| rHuEPO | DRUG | 150 IU/kg TIW |
| Darbepoetin alfa and Epoetin alfa | DRUG | - |
| IV iron dextran | DRUG | Administered by intravenous (IV) injection. |
| recombinant human erythropoietin (rHuEPO) | DRUG | - |
| Recombinant Human Erythropoietin | DRUG | - |
| Darbepoetin alfa SC | DRUG | Subcutaneous (SC) injection of darbepoetin alfa at 4.5 mcg/kg weekly for weeks 1-6, then 4.5 mcg/kg Q3W |
| Darbepoetin alfa IV | DRUG | Intravenous administration of darbepoetin alfa at 4.5 mcg/kg weekly for weeks 1-6, then 4.5 mcg/kg Q3W |
Inclusion Criteria: * Subject or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/ procedures being initiated; * Subject must continue long term follow up within parent study (20090160); * Subject must have an ongoing clinically releva...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 2 | PHASE3 | Luspatercept |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 2 | PHASE3 | Elritercept |
| Disc Medicine, Inc. | IRON | 2 | PHASE2 | DISC-0974 |
| Akebia Therapeutics, Inc. | AKBA | 2 | PHASE3 | Vadadustat |
| Sunshine Biopharma Incorporated | SBFM | 1 | PHASE2 | HEC53856, rHuEPO |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | APG-5918 |
| Bayer | BAYRY | 1 | - | Molidustat |
Darbepoetin alfa is used to treat anemia, including anemia in chronic kidney disease patients not on dialysis. It is also studied in blood cancers such as myelodysplastic syndrome and in patients with cancer receiving chemotherapy. Its development spans chronic kidney disease, breast cancer, and other cancer-related anemia settings.
Darbepoetin alfa targets EPOR, the erythropoietin receptor, and acts as a receptor agonist. By binding and activating this receptor, it stimulates erythropoiesis, the production of red blood cells, which is the basis for its use in treating anemia across the studied patient populations.
Darbepoetin alfa is developed by Amgen Inc., which trades under the ticker AMGN. Amgen is the company behind the drug's clinical development program, which includes 16 completed trials enrolling a total of 4,474 participants across anemia and cancer-related indications.
Darbepoetin alfa is in Phase 3 development. Its clinical program includes 16 completed trials, all of which are Phase 3, with no active trials currently listed. The studies were randomized, double-blind, and active-controlled, and enrolled 4,474 participants in total.
Completed Phase 3 trials include NCT03776032 in lung cancer patients with anemia receiving platinum-based chemotherapy, NCT01652872 in chronic kidney disease patients not on dialysis, NCT01362140 in low or intermediate-1 risk myelodysplastic syndrome, and NCT02175277, an MDS companion protocol conducted in Belgium.