Validation of the BIACORE 3000 platform for detection of antibodies against erythropoietic agents in human serum samples

OBJECTIVE: To develop a validated BIACORE immunoassay for the detection and characterization of serum antibodies with specificity for erythropoietic molecules (e.g. darbepoetin alfa). METHODS: New Zealand White rabbits (n = 8) were immunized by an intramuscular injection of darbepoetin alfa/adjuvant at 0, 4, 6, and 8 weeks. Serum was collected for 6 weeks after final injection and pooled for affinity purification. Antibody immunoassay measurements were performed using a BIACORE 3000 with darbepoetin alfa immobilized to the biosensor surface. Human serum samples were spiked with the affinity-purified rabbit antibody to develop and validate the BIACORE immunoassay. RESULTS: The assay was shown to be stable through 180 sample/regeneration cycles and had a threshold of 45.8 response units. The validated limit of detection was 0.40 microg/ml in 100% human serum. The method was robust, with variability not exceeding a 20% coefficient of variation, well within acceptable limits for typical immunoassays. CONCLUSION: All protein-based therapeutics have a potential for immunogenicity, and antibodies raised against these molecules may have important clinical sequelae. The biotechnology and pharmaceutical industries are challenged to address this potential by developing robust analytical platforms to detect and characterize antibodies directed against therapeutic proteins in clinical specimens. Traditionally, radioimmune precipitation assays and/or enzyme-linked immunoassays (ELISAs) are used for primary detection of host immune response; however, the BIACORE platform may be better suited for this purpose in many instances. This platform represents a robust tool that should be considered for the detection and characterization of antibodies directed against protein-based therapeutics.     

The development and validation of a sensitive,dual-flow cell,SPR-based biosensor immunoassay for the detection,semi-quantitation,and characterization of antibodies to darbepoetin alfa and epoetin alfa in human serum

A surface plasmon resonance (SPR)-based biosensor immunoassay was developed and validated using the Biacore 3000 instrument to detect, semi-quantitate, and characterize serum antibodies against darbepoetin alfa (Aranesp^®) and epoetin alfa (EPOGEN^®). In this sensitive, dual-flow cell assay, epoetin alfa and darbepoetin alfa are covalently immobilized onto consecutive flow cells of a carboxymethyl dextran-coated sensor chip. Diluted human serum samples are injected sequentially over both surfaces. The binding of serum antibodies to the immobilized proteins are detected and recorded in real time based on the principles of SPR. Furthermore, antibody binding is confirmed with a secondary anti-human immunoglobulin antibody. Positive samples are further characterized to determine the relative concentration of the antibodies using an affinity-purified, rabbit anti-epoetin alfa antibody as a reference control.     

The relative dosing of epoetin alfa and darbepoetin alfa in chronic kidney disease

ABSTRACT

Objective: The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa: darbepoetin alfa dose ratios across studies.

Methods: A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000–2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated.

Results: A total of 21 studies involving 16?378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:µg of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1.

Conclusions: Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11–18% cheaper than treatment with darbepoetin alfa in Canada.     

A randomised,cross-over study comparing injection site pain with subcutaneous epoetin beta and subcutaneous darbepoetin alfa in patients with chronic kidney disease*

ABSTRACT

Objective: To compare injection site pain of subcutaneous (sc) epoetin beta and darbepoetin alfa in adult patients with chronic kidney disease.

Research design and methods: This was a multi-centre, randomised, two-arm, single-blind, cross-over study. Patients were randomised to receive weekly sc darbepoetin alfa 30?μg or weekly sc epoetin beta 6000?IU for 2 weeks and were then crossed over to the alternative treatment for 2 weeks. Injection site pain was assessed using a 10?cm ungraduated visual analogue scale (0?=?no pain, 10?=?worst pain) and a six-point verbal rating scale. Patient preference for treatment was also assessed.

Trial registration: http://clinicaltrials.gov/(NCT00377481).

Results: All randomised patients (N?=?48) completed the study. The sample comprised 29 chronic kidney disease patients (Stage 3 or Stage 4), 11 peritoneal dialysis patients and 8 renal transplant patients. Patients perceived significantly less pain with epoetin beta than darbepoetin alfa, using the visual analogue scale (relative pain score?=?2.75, darbepoetin alfa:epoetin beta, 95% CI: 1.85, 4.07; p?<?0.0001) and the verbal rating scale (median: 0.5, 95% CI: 0.5, 1.0 vs. median: 1.5, 95% CI: 1.0, 2.0; p?<?0.0001). Epoetin beta was preferred by significantly more patients (65%) than darbepoetin alfa (10%) (p?<?0.001); 25% of patients reported no preference.

Conclusions: Limitations included lack of an epoetin alfa comparator and limited blinding (patients were blinded to treatment, however, an unblinded nurse administered treatment). We show that sc injection of epoetin beta is significantly less painful than darbepoetin alfa and patient preference for epoetin beta confirms that the difference is clinically meaningful.     

Improved Haemoglobin Concentrations with IV Darbepoetin alfa - Case Studies of Haemodialysis Patients

Summary

This paper presents two case histories of patients receiving intravenous (IV) darbepoetin alfa for the treatment of anaemia in chronic renal

failure. The paper sets these cases against the general clinical picture of patients receiving intravenous darbepoetin alfa in our renal unit.     

Anemia treatment with Q2W darbepoetin alfa in patients with chronic kidney disease naïve to erythropoiesis-stimulating agents*

ABSTRACT

Objective: To evaluate the efficacy and safety of darbepoetin alfa dosed every-other-week (Q2W) to treat anemia in subjects with chronic kidney disease (CKD), not receiving dialysis, who were naïve to erythropoiesis-stimulating agent (ESA) therapy.

Research design and methods: This was an open-label, multicenter, single-arm study enrolling ESA-naïve CKD subjects with baseline hemoglobin (Hb)?<?11.0?g/dL. Q2W darbepoetin alfa treatment was initiated at a dose of 0.75?µg/kg and titrated to achieve and maintain Hb levels at 11.0–13.0?g/dL. Treatment was administered from week 1 to week 19.

Main outcome measures: The primary endpoint was the proportion of subjects who achieved Hb?≥?11?g/dL at any study visit, except in week 1. Hb levels, darbepoetin alfa dose, and safety were also assessed.

Results: Of the 128 subjects who received at least one dose of darbepoetin alfa and of the subjects who completed the study, 118 (92%) and 112 (97%), respectively, achieved a Hb?≥?11?g/dL in a median time of 5 weeks. Median darbepoetin alfa dose at week 1 and at the time of achieving a Hb?≥?11?g/dL were 60 and 80?µg, respectively. Darbepoetin alfa was well-tolerated, and short-term adverse events were consistent with those expected in CKD subjects.

Conclusions: This study demonstrates that de novo Q2W darbepoetin alfa was effective in correcting and maintaining Hb levels in ESA-naïve subjects with CKD who were not receiving dialysis. Study limitations, including lack of a control arm for the study and multiple race information for subjects, must be considered in interpreting the results.

Trial registration: ClinicalTrials.gov identifier: NCT00112008.     

Subcutaneous injection pain with C.E.R.A., a continuous erythropoietin receptor activator,compared with darbepoetin alfa

ABSTRACT

Objective: This study assessed injection site pain following subcutaneous (SC) administration with a continuous erythropoietin receptor activator (C.E.R.A.), compared with darbepoetin alfa in healthy adults.

Methods: In a randomized, placebo-controlled, single-centre, single-blind, three-way crossover study, subjects received one of six treatment sequences (ABC/ACB/BAC/BCA/CBA/CAB) involving SC injection of (A) C.E.R.A. 50?μg, (B) darbepoetin alfa 50?μg, or (C) placebo on days 1, 29, and 57. An initial pilot phase (n = 12) was used to determine the sample size for the confirmatory phase (n = 72), and data were combined for the final analysis (n = 84).

Main outcome measures: The primary endpoint was pain on the 100?mm visual analog scale (VAS) immediately after dosing. Secondary endpoints included VAS at 1 hour after dosing and pain on the six-point verbal rating scale (VRS) immediately and at 1 hour after dosing.

Results: C.E.R.A. was associated with significantly less pain immediately after SC injection compared with darbepoetin alfa: least squares mean VAS 21.5 (95% confidence interval [CI]: 17.5, 25.5) versus 33.4 (95% CI: 28.4, 38.4) (?p < 0.0001). Incidence of pain on the VRS was lower with C.E.R.A. compared with darbepoetin alfa immediately after dosing (?p < 0.0001). One hour after administration, most subjects had no VRS pain. A study limitation is the small sample size and the findings need to be confirmed in a large trial of chronic kidney disease patients.

Conclusions: SC injection with C.E.R.A. is significantly less painful than SC darbepoetin alfa in healthy adults. Treatment of anemia in chronic kidney disease with SC injection of C.E.R.A. may provide a lower pain burden compared with darbepoetin alfa.     

Randomized,double-blind,placebo-controlled trial of every-3-week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia

ABSTRACT

Objective: Darbepoetin alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA.

Research design and methods: Patients aged?≥?18 years with anemia (hemoglobin <11?g/dL) being treated for nonmyeloid malignancy were randomized 1:1 to receive darbepoetin alfa 300?μg (n?=?193) or placebo (n?=?193) subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules.

Main outcome measures: The primary endpoint was the proportion of patients who received ≥1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the proportions of patients achieving a hemoglobin concentration ≥11?g/dL and subsequently maintaining hemoglobin levels above 11?g/dL, and the change in hemoglobin concentration over time.

Results: The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of patients, a 16.3% difference, p?<?0.001). There were no differences between the two treatment arms in quality-of-life measures. Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels. Study limitations suggest caution in the interpretation of these results: transfusions, the primary endpoint, were recommended but not required if hemoglobin concentrations were ≤8.0?g/dL, and protocol deviations (primarily dosing errors) occurred in approximately one-half of the patients in both treatment groups.

Conclusions: In this study, fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA.

Trial registration: ClinicalTrials.gov identifier: NCT00110955.     

The association of darbepoetin alfa with hemoglobin and health-related quality of life in patients with chronic kidney disease not receiving dialysis

ABSTRACT

Objective: Anemia of chronic kidney disease (CKD) decreases patients’ health-related quality of life (HRQoL). The objective of this subanalysis was to determine the effect of every-other-week (Q2W) darbepoetin alfa on hemoglobin (Hb) levels and HRQoL measures in subjects with CKD who are naïve to erythropoiesis-stimulating agents (ESAs).

Methods: STAAR was a 52-week, multicenter, single-arm study. Subject inclusion criteria included: ≥?18?years of age and creatinine clearance ≤?70?mL/min or estimated glomerular filtration rate ≤?60?mL/min/1.73 m² but not receiving dialysis. Subjects included in this subanalysis were previously naïve to ESAs, had Hb <?11?g/dL, were initiated on subcutaneous Q2W darbepoetin alfa to achieve a Hb level not to exceed 12?g/dL, and had responses to at least one question on the KDQOL-CRI forms administered at baseline, week 12, and week 52.

Results: Of 911 ESA-naïve subjects enrolled in the study, 277 (30.4%) were included in this subanalysis. The majority of subanalysis subjects were Caucasian (63.2%) and/or women (54.5%). Mean Hb concentrations and all KDQOL-CRI scores improved significantly between baseline and week 12 (?p < 0.0001), and were maintained until week 52. Darbepoetin alfa was well tolerated.

Conclusions: Darbepoetin alfa initiated Q2W achieved and maintained Hb targets, and significantly improved and maintained HRQoL in study subjects with CKD. Limitations of the study must be considered when extrapolating these results to assess the benefits of treatment on HRQoL in the general CKD population.     

Preference for monthly darbepoetin alfa dosing in patients with chronic kidney disease not receiving dialysis

ABSTRACT

Objective: To determine patient preference for once-weekly Epoetin alfa versus once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD) not receiving dialysis.

Methods: AMPS (Aranesp Monthly Preference Study) consisted of two studies of similar design, each with a 2-week screening/baseline period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up period. Patients aged ≥18 years had a nephrologist-reported diagnosis of CKD but were not receiving dialysis, and were required to have at least two hemoglobin levels within 10–12?g/dL and to have been receiving a stable dose (< 25% change) of once-weekly or once- every-other-weekly Epoetin alfa for at least 8 weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back to their previous Epoetin alfa regimen. The primary analysis assessed patient preference at week 21 for QM darbepoetin alfa versus previous onceweekly Epoetin alfa.

Results: AMPS enrolled 442 patients: 54% were female, 67% were Caucasian, and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161) preferred darbepoetin alfa QM, and of all patients who expressed a preference, regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to mean hemoglobin at baseline (for those who completed the study and were receiving QM darbepoetin alfa at week 29: 11.2 [1.1]?g/dL at week 29 versus 11.4 [0.7]?g/dL at baseline). QM darbepoetin alfa was well tolerated.

Conclusion: These data show that the majority of study patients preferred QM darbepoetin alfa to more frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels at week 29 and was well tolerated over the study period. The single-item questionnaire could be a potential limitation of this study and further investigation with a multi-question instrument may be helpful in confirming these results.     

Use and cost of erythropoiesis-stimulating agents in patients with cancer

ABSTRACT

Objective: To compare the baseline characteristics, episodes of care, and cost of erythropoiesis-stimulating agents among cancer patients in a US managed-care population.

Research design and methods: Retrospective analysis of administrative claims data. Episodes of care for patients with cancer receiving erythropoiesis-stimulating agents between January 1, 2004 and January 17, 2006 included all claims for erythropoiesis-stimulating agents with ≤42 days’ gap between claims, plus the duration of therapeutic benefit based on median days between consecutive doses.

Main outcome measures: Main outcome measures were average weekly dose of erythropoiesis-stimulating agents and costs of therapy.

Results: A total of 15?007 eligible episodes of care (darbepoetin alfa, 7769 episodes [5587 patients]; epoetin alfa 7238 episodes [5157 patients]) were identified. Fewer claims were observed per episode of care for darbepoetin alfa than for epoetin alfa (mean [SD] 3.7 [4.1] vs. 5.3 [6.4]). The median time between consecutive claims was 15 days (darbepoetin alfa) and 8 days (epoetin alfa). The mean (SD) weekly doses were 105 (56)?μg (darbepoetin alfa) and 34?242 (28173) U (epoetin alfa), a dose-comparison ratio of 326?:?1.

Dose-comparison ratios were sensitive to assumptions about duration of clinical benefit.

The mean (95% CI) weekly costs were significantly lower for darbepoetin alfa ($560 [553–567]) than for epoetin alfa ($645 [630–659], p < 0.0001) when duration of clinical benefit was considered.

Conclusions: Significant differences characterize patterns of use of erythropoiesis-stimulating agents. Duration of therapeutic benefit is an important variable in comparing darbepoetin alfa with epoetin alfa; incorporation of this variable in analyses of costs of therapy may have notable effects on calculated treatment costs. Limitations of the study include the potential for database errors or omissions, lack of detailed disease data, and lack of adjustment for differences in the ages and comorbidities of patients.     

The advantages of intravenous renal anaemia treatment in an undernourished patient with chronic kidney disease

SUMMARY

The subcutaneous (SC) treatment of renal anaemia in undernourished patients has potential limitations. In this case report we demonstrate the value of intravenous (IV) darbepoetin alfa in such a patient who experienced difficulty tolerating SC recombinant human erythropoietin (rHuEPO) therapy due to severe malnutrition. Intravenous treatment of renal anaemia in a malnourished patient is preferred because the absence of SC fat makes SC administration difficult. In such patients, darbepoetin alfa is the treatment of choice as it is administered less frequently than other erythropoietic therapies and yis more effective at maintaining target haemoglobin (Hb) concentrations. In contrast to rHuEPO, darbepoetin alfa also has the additional advantage of bioequivalent IV and SC dose requirements.     

Dosing patterns,hematologic outcomes,and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia

ABSTRACT

Objective: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting.

Methods: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for ≥ 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24‐week study period.

Results: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (≥ Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (≥ 11?g/dL) (?p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24‐week cumulative doses were EPO 279?336 ± 68?302 units and DARB 1084 ± 246?µg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = $3400, DARB = $4726; FSS: EPO = $1528, DARB = $2379).

Conclusions: Extended dosing (≥ Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39–56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.     

A randomized,controlled trial comparing darbepoetin alfa correction/maintenance dosing with weekly dosing for treating chemotherapy-induced anemia

ABSTRACT

Objective: To evaluate if a darbepoetin alfa correction/maintenance dosing regimen is non-inferior to a weekly regimen with respect to red blood cell trans­fusion requirements in patients with chemotherapy-induced anemia (CIA).

Research design and methods: In this randomized, active-controlled, double-blind phase 3 trial, CIA patients were randomized 1?:?1 to receive darbepoetin alfa in either a correction/maintenance schedule (4.5?μg/kg weekly for 4 weeks followed by 4.5?μg/kg every 3 weeks (Q3W)) or a weekly schedule (2.25?μg/kg weekly). The primary endpoint was the transfusion incidence during weeks 1–16. Non-inferiority was to be concluded if the upper limit of the 95% confidence interval (CI) of the difference in transfusion incidence between treatment groups was below 12.5%. Hematologic responses and safety profiles were also compared.

Results: Transfusion incidence (95% CI) during weeks 1–16 was 37% (32–42) and 38% (32–43) in the weekly and correction/maintenance groups, respectively. The difference (95% CI) in transfusions was 0.4% (–7.0 to 7.8), demonstrating non-inferiority between treatment groups. Similar percentages in both groups achieved and maintained hemoglobin in a target range of 11–13?g/dL and had clinically meaningful FACT?F score improvements. The median (range) time to hemoglobin response was 10 (1–17) weeks and 12 (2–17) weeks in the weekly and correction/maintenance groups, respectively. Both groups had similar safety profiles.

Conclusions: A correction/maintenance schedule with its initial two-fold higher weekly dosing and subsequent Q3W dosing yielded outcomes similar to those observed with a weekly schedule. Although correction/maintenance dosing provided no incremental clinical benefit, Q3W dosing could provide benefits of convenience and facilitate patient compliance.     

A prospective,observational study describing the haematological response in patients undergoing chemotherapy treated by tri-weekly darbepoetin alfa for anaemia

Abstract

Objective:

This prospective, observational study investigated the haematological response to darbepoetin alfa (DA) administered every three weeks for the treatment of anaemia. Response was also assessed according to baseline characteristics including iron, folate and vitamin B12 status.     

Dosing patterns,drug costs,and hematologic outcome in anemic patients with chronic kidney disease switching from darbepoetin alfa to epoetin alfa

ABSTRACT

Objective: To compare real-world dosing patterns, drug costs, and hematologic outcome in anemic chronic kidney disease (CKD) patients, not receiving dialysis, who switched from darbepoetin alfa (DARB) to epoetin alfa (EPO) in a community practice setting.

Research design and methods: This retrospective observational chart review from a US nephrology clinic included 153 anemic CKD patients ≥ 18 years of age who did not receive dialysis during the study period, switched from DARB to EPO between 8/2003 and 8/2005, and received ≥ 2 doses of both agents. Paired t-test and McNemar's chi-square were performed comparing pre-switch and post-switch outcomes.

Results: Mean interval between doses increased from 24.3 ± 11.1 days with DARB to 28.8 ± 19.8 days with EPO (?p = 0.001). Weighted mean pre-switch weekly dose for DARB was 25?µg, while weighted mean post-switch weekly dose for EPO was 7090 Units, resulting in a dose ratio (Units EPO:µg DARB) of 287:1. These doses resulted in mean weekly costs of $110 (DARB) and $86 (EPO). Mean hemoglobin (Hb) levels increased over time from 10.8?g/dL at 6 months pre-switch to 11.1?g/dL 6 months after EPO initiation (?p = 0.0132). Mean Hb levels were > 11?g/dL, but below 12?g/dL, while patients received EPO.

Conclusions: Patients switching from DARB to EPO had a greater mean interval between doses, lower drug costs, and consistently maintained recommended Hb levels over time.

Limitations: The reverse direction (EPO to DARB) was not investigated. Although treatment outcomes were not assessed in a randomized, controlled setting, the study's observational nature provided actual evidence in a real-world setting.     

Clinical and economic comparison of epoetin alfa and darbepoetin alfa

SUMMARY

Background: The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy.

Methodology: Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted.

Results:To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy.

Conclusion: These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.     

Current and future options for the treatment of chemotherapy-induced anaemia

Chemotherapy-induced anaemia (CIA) is a significant source of morbidity in patients receiving treatment for cancer. There are three products currently available for the treatment of CIA: epoetin alfa, epoetin beta and darbepoetin alfa. Several organisations have published recommendations for the use of these agents. Several randomised, controlled trials have been conducted comparing the most popular dosing regimens of epoetin alfa and darbepoetin alfa, with conflicting results. Information regarding survival and adverse event data related to these agents continues to create debate. This review considers four new agents that are under development for the treatment of CIA.     

Chemotherapy-induced anemia: the story of darbepoetin alfa

Abstract

Background:

Prior to the approval of the first erythropoiesis-stimulating agent (ESA) in the early 1990s, red blood cell transfusions were the primary means of treating severe chemotherapy-induced anemia (CIA), with little recourse for those with more mild forms of the condition. The introduction of the ESAs allowed treatment of mild-to-moderate CIA in patients with cancer. It has been a decade since darbepoetin alfa (DA), a second-generation ESA with a longer half-life, became available to patients with CIA.