Biosimilar Epoetin Alfa Research Articles

Retacrit®, Biosimilar of Epoetin Alfa, in Chemotherapy-Induced Anemia in Routine Practice: Impact of Iron Supplementation.

The aim of the study was to evaluate in real-life conditions the effectiveness and safety of a biosimilar of epoetin alfa (Retacrit®) in chemotherapy-induced anemia and the impact of iron supplementation. This was a longitudinal, observational, prospective study of 12-16 weeks conducted in 195 French centers. The primary endpoint was the achievement of target Hb (with an increase of Hb ≥1 g/dL) or an increase of Hb ≥2 g/dL, in the absence of transfusion in the previous 3 weeks. 2,076 patients (women, 50.6%; mean age, 67.0 years) with malignant diseases (solid tumors, 79.8%; lymphomas, 12.7%; multiple myeloma, 6.6%) were analyzed. A total of 655 patients received oral iron (40.5%), intravenous iron (58.9%), or both (0.6%). At inclusion, 10.0% and 18.2% of patients without and with iron supplementation had serum ferritin <100 μg/L, respectively. Transferrin saturation (TSAT) ≤20% was more frequent in patients with supplementation (76.6%) than without supplementation (33.9%). The mean weekly doses of epoetin alfa biosimilar and planned duration of treatment were comparable regardless of iron supplementation. The primary endpoint was achieved in 70.5% and 70.2% of patients without and with iron supplementation, respectively. Three (0.1%) serious thromboembolic events related to treatment with epoetin alfa biosimilar were reported. Epoetin alfa biosimilar was effective and well tolerated for treating chemotherapy-induced anemia. Patients in subgroup with iron supplementation had lower TSAT at inclusion compared to subgroup without supplementation. Comparable mean Hb levels were achieved in both subgroups. The rate of patients with iron supplementation through the intravenous route was however insufficient.

Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta-Analysis

Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar). The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology. We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence. We identified 28 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 9 cohort studies (total N = 23,043) of G-CSF biosimilars [corrected]. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses. Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.

1790P - Correlation between fatigue evaluated with a visual analog scale (VAS) and quality of life (QoL) in cancer patients treated with biosimilar epoetin alfa for chemotherapy-induced anemia (CIA): The CIROCO study

Background: Anemia often occurs in cancer patients receiving chemotherapy. QoL can be affected by symptoms of anemia, fatigue being the most common. Evaluation of QoL with validated tools (eg EORTC QLQ C30) is time-consuming. Correlation between fatigue assessed with a VAS and QoL is unclear. Aim: To determine the correlation between fatigue assessed by a VAS and QoL in cancer patients treated with biosimilar epoetin alfa (Sandoz) for CIA. Methods: CIROCO is a non-interventional, prospective, multicenter study of adult patients (Full Analysis Set [FAS] population, n = 538) with ≥2 cycles of chemotherapy planned after study inclusion, with CIA and receiving biosimilar epoetin alfa. Data were collected on day of inclusion (T0), and after 2–3 (follow-up; T1) and 4–6 chemotherapy cycles (end of follow-up; T2). Patients and physicians separately assessed fatigue using a VAS (range 0–10); patients assessed QoL with the EORTC QLQ C30 questionnaire. Results: Data are reported for a subgroup of patients with solid tumors (FAS population, n = 434). Mean (SD) hemoglobin (Hb) at baseline was 9.7 (±0.8) g/dL. Mean (SD) increase in Hb was 1.2 (±1.4) g/dL between T0 and T1 and 0.4 (±1.5) g/dL between T1 and T2. In the safety population (n = 464), 151 (32.5%) had adverse events (AEs; n = 320), 64 patients (13.8%) had serious AEs (n = 144) and 14 patients (3%) experienced AEs considered related to study treatment (n = 25). In the FAS population, between T0 and T2, mean (SD) change in fatigue VAS score (patient-reported) was +5.2 (±92.6) % and mean (SD) change in QoL was 29.9 (±98.0) %. The Pearson correlation coefficient for fatigue VAS score and QoL was –0.4993 (p < 0.0001) at T0, –0.5726 (p < 0.0001) at T1, and –0.5681 (p < 0.0001) at T2. Using fatigue VAS, physician assessment of fatigue was consistent with patient perceptions at T0 (5.0±2.1 vs 5.3±2.2), T1 (4.3±2.2 vs 4.8±2.3) and T2 (4.2±2.3 vs 4.7±2.3). Conclusions: Biosimilar epoetin alfa was effective in this study, with improvements observed in Hb and QoL. A correlation was observed between reduced fatigue assessed with a VAS and improved QoL. Editorial acknowledgement: Tony Reardon, Spirit Medical Communications Ltd. Legal entity responsible for the study: Sandoz SAS. Funding: Sandoz SAS. Disclosure: N. Baize: Steering Committee member: CIROCO study. All other authors have declared no conflicts of interest.

PSY111 - PHARMACOECONOMIC EVALUATION OF BIOSIMILAR RECOMBINANT ALPHA-EPOETIN IN THE TREATMENT OF ANEMIA IN HEMODIALYSIS PATIENTS

To perform an economic evaluation of biosimilar epoetin alpha (EPO α), originator darbepoietin alpha (DARB) and pegylated epoetin beta – (continuous erythropoietin receptor activator, CERA) in patients on haemodialysis (HD). administration of erythropoiesis stimulating agent (ESAs) is the standard of care for treatment of anemia in hemodialysis patients. a cost-minimization analysis was performed in adult outpatients treated with ESAs for anemia due to CKD. Direct costs of ESA treatment were calculated for one hemodialysis patients. A Decision tree model was developed to compare cost for intravenous maintenance dose (median weight - 75 kg) between the drug arms: biosimilar EPO α 33.3 ME/kg three times-weekly, DARB 0.5 mkg/kg once weekly and CERA 60 mkg every two weeks (Q2W) or 120 mkg per month. Unit costs for drugs: EPO α 2500 ME, DARB 20 and 30 mkg and CERA 50, 75 and 150 mkg vial were estimated from national published sources (exchange rate mean in 2018 - €1 = 71.8 RUB). One-way sensitivity analyses were performed to test model robustness. total annual cost for short-acting biosimilar epoetin alfa was €821, for originator DARB - from €4,559 to €5,556 (for 20 mkg and 30 mkg vial respectively) and for originator CERA treatment - from €1,846-1,999 (for patients not currently treated with an ESA) to €2,269 – €2,917 (for CERA after previous weekly short-acting epoetin alfa with dose >8000 units per week). Therefore, the use of intravenous biosimiliar epoetin alfa could be associated with a cost-saving of 56-85% with the assumption that all ESA have similar effectiveness. The sensitivity analysis showed that the results are stable under a wide range of assumptions. managing hemodialysis patients with biosimilar epoetin alfa is consistently cost saving over treatment with originator epoetin alfa and darbepoetin alfa.

Structure-Function Relationships for Recombinant Erythropoietins: A Case Study From a Proposed Manufacturing Change With Implications for Erythropoietin Biosimilar Study Designs

Comparability studies used to assess a proposed manufacturing change for a biological product include sensitive analytical studies to confirm there are no significant differences in structural or functional attributes that may contribute to clinically meaningful changes in efficacy or safety. When a proposed change is relatively complex or when clinically relevant differences between the product before and after the change cannot be ruled out based on analytical studies, nonclinical and clinical bridging studies are generally required to confirm overall comparability. In this study, we report findings from a comparability assessment of epoetin alfa before and after a proposed manufacturing process change. Although differences in glycosylation attributes were observed, these were initially believed to be irrelevant to the product's pharmacology. This assumption was initially supported via nonclinical and clinical pharmacology studies, but a clinically meaningful difference in potency was ultimately observed in a phase 3 clinical study conducted in a sensitive patient population using a sensitive study design. These results indicate that the nonclinical assessments of structure-function relationships were insufficiently sensitive to identify clinically relevant differences resulting from differences in the glycosylation profile. This case study highlights important findings that may be relevant in the development of biosimilar epoetin alfa products.

HX575: established biosimilarity in the treatment of renal anemia and 10 years of clinical experience.

Erythropoiesis-stimulating agents, such as recombinant human erythropoietin, are commonly used for the treatment of anemia in patients with chronic kidney disease (CKD). In 2007, HX575 (Binocrit®) became the first biosimilar epoetin alfa to be approved by the European Medicines Agency (EMA). The decision to approve a biosimilar is based on the totality of evidence obtained in a comprehensive comparability exercise that involves extensive analytical characterization, nonclinical studies and clinical studies. The development process for HX575 included extensive analytical characterization and comparison with the reference epoetin alfa. This was followed by a clinical development program, comprising Phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine and a confirmatory Phase III study to demonstrate therapeutic effectiveness in anemia related to CKD. In addition to the comparability exercises, extensive clinical experience over the last decade also confirms that HX575 provides an effective treatment for CKD-related anemia, with a favorable safety profile. Growing clinical experience with EMA-approved biosimilars, including HX575, should offer additional reassurance to health care professionals and patients that these agents are as effective and well tolerated as others in the therapeutic class.

A Comparison of the Safety and Efficacy of HX575 (Epoetin Alfa Proposed Biosimilar) with Epoetin Alfa in Patients with End-Stage Renal Disease

Background: HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia. Methods: This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28). Results: Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was –0.093 g/dL, with 90% CI (–0.23 to 0.04) entirely within the pre-specified equivalence limits (–0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies. Conclusions: SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety.

1594P - Biosimilar epoetin alfa (HX575) for the treatment of chemotherapy-induced anaemia: Development, approval and 10 years’ clinical experience

1594P - Biosimilar epoetin alfa (HX575) for the treatment of chemotherapy-induced anaemia: Development, approval and 10 years’ clinical experience

Biosimilars: Implications for Clinical Practice.

In 2015, the United States Food and Drug Administration (FDA) approved the first biosimilar, filgrastim-sndz, a biosimilar of the granulocyte colony-stimulating factor filgrastim. Since that time, the FDA has approved four additional biosimilar tumor necrosis factor α inhibitors, and, in May 2017, the Oncology Drug Advisory Committee voted in favor of approval of an epoetin alfa biosimilar. The patents of several widely used biologic cancer therapies (including trastuzumab, rituximab, bevacizumab, cetuximab, and pegfilgrastim) are recently expired or due to expire in the near future, so the introduction of biosimilars into the oncology treatment armamentarium is imminent. However, their arrival also will introduce challenges, including pharmacy and supply chain management and the need for education of clinicians and patients about the efficacy and safety of these agents. These considerations, along with an overview of biosimilars in the oncology pipeline, will be discussed in this review.

Biosimilar epoetin alfa increases haemoglobin levels and brings cognitive and socio-relational benefits to elderly transfusion-dependent multiple myeloma patients: results from a pilot study

Anaemia is a complication reported in up to 70% of the multiple myeloma patients (MM), with remarkable clinical, cognitive and socio-relational consequences. Anaemia relates to the course of MM, normalizing in patients during remission and reappearing in relapsing/non-responding patients. In a pilot study with 31 patients with MM and transfusion-dependent anaemia, we evaluated the effects of Binocrit (biosimilar epoetin alfa) on transfusions, haemoglobin levels, mental status (mini-mental state evaluation) and the patients' social-relational functioning and quality of life (QoL). Within a 12-week interval, patients received 40.000U Binocrit once a week. Binocrit significantly decreased the incidence of transfusion, regardless of the patients' transfusion history, and significantly increased haemoglobin levels (before-and-after-treatment median haemoglobin values = 8.20 vs. 9.40g/dl, respectively; Wilcoxon Z test, p<.001). A comparatively greater increment in haemoglobin levels among patients who responded to first vs. additional lines of chemotherapy was also observed. Importantly, we additionally found moderate-to-strong positive associations between increments in haemoglobin levels and corresponding increments both in psychological well-being and QoL (FACT-An scores) and the patients' cognitive status (mini-mental state evaluation scores). After statistically controlling for possible concurrent benefits of anti-myeloma therapy, increments in haemoglobin levels clearly predicted both increments in socio-relational FACT-An scores (Spearman's rho=0.60, p<.001) and in cognitive functioning scores (Spearman's rho=0.49, p<.006). Binocrit thus appears as an effective, well-tolerated agent for the management of myeloma anaemia, whose documented benefits include amelioration of anaemia, reduction in transfusion, and improvements in the patients' social-relational functioning and cognitive well-being.

Management of anaemia in oncohaematological patients treated with biosimilar epoetin alfa: results of an Italian observational, retrospective study.

Many patients with solid tumours or nonmyeloid haematopoietic tumours develop symptomatic anaemia, which has a major impact on quality of life (QoL). The efficacy of erythropoiesis-stimulating agents (ESAs) in improving QoL and reducing blood transfusions has been widely demonstrated. Binocrit® (biosimilar epoetin alfa) is an ESA indicated in the European Union for treating chemotherapy-induced anaemia. The aim of this study was to investigate the effect of Binocrit® on haemoglobin (Hb) levels in anaemic cancer patients in Italian clinical practice. The ANEMONE study was a national, longitudinal, retrospective, multicentre observational study. Patients had to be 18 years or older, with a solid tumour or non-Hodgkin's lymphoma, Hodgkin's disease or multiple myeloma, receiving chemotherapy, and treated with Binocrit® to manage chemotherapy-induced anaemia. The primary outcomes were the proportion of patients with a Hb increase ⩾1 g/dl during the first 4 weeks and with a Hb increase ⩾2 g/dl during the first 12 weeks. A total of 245 patients were enrolled and 215 patients were evaluable for statistical analysis. In the first 4 weeks, 49.3% of patients showed an increase in Hb of ⩾1 g/dl: 45.5% in patients with solid tumours and 52.1% in patients with haematological malignancies. In the first 12 weeks, 51.6% of patients showed an increase in Hb of ⩾2 g/dl (48.4% solid tumours, 54.2% haematological diseases). Treatment with Binocrit® was well tolerated. These results confirm the effectiveness and safety of Binocrit® for chemotherapy-induced anaemia in routine practice in patients with solid tumours, lymphoma and myeloma.

Abstract P1-10-02: Usage of epoetin alfa biosimilars in the management of chemotherapy-induced anemia in patients with breast cancer: A subanalysis of the ORHEO study

Abstract Introduction Chemotherapy-induced anemia (CIA) is a frequent complication of breast cancer patients that is associated with fatigue and impaired quality of life. Biosimilars of erythropoietin-stimulating agents have now been approved to treat CIA in Europe. The ORHEO (biOsimilaRs in the management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was an observational study conducted in France to evaluate the efficacy and safety of a biosimilar epoetin alfa in an oncology setting. The large number of patients who enrolled in the study permitted indication-specific subanalyses to be undertaken. Herein we report the results of the subanalysis that focuses on the subpopulation of breast cancer patients. Methods The ORHEO study was a prospective, observational, longitudinal, multicenter postmarketing study. Patients ≥18 years with CIA (hemoglobin [Hb] &amp;lt;11 g/dL)-associated solid tumors, lymphomas, or myelomas who were eligible for treatment with an epoetin alfa biosimilar were enrolled. The primary endpoint was Hb response (defined as Hb reaching ≥10 g/dL, an increase of Hb ≥1 g/dL since inclusion, or reaching target Hb) measured at 3 and 6 months (M3 and M6, respectively). Secondary endpoints included safety and tolerability. Only breast cancer patients with CIA were included in this subanalysis. Results The ORHEO study enrolled 2333 patients; of these, 266 patients presented with CIA associated with breast cancer and were included in this subanalysis. The mean age was 61 years, the majority had ECOG PS 1 (51.5%) and metastatic disease (56.0%), and 99.6% received an epoetin alfa biosimilar. At baseline, the mean Hb level was 9.9 g/dL. At the M3 and M6 time points, an Hb response was observed in 86.8% and 91.7% of patients, respectively; average Hb levels increased by 1.3 g/dL (M3) and 1.8 g/dL (M6). By M3, 44% of patients reached their target Hb level; this increased to 53.7% at M6. At M3 and M6, of those patients who definitively or temporarily discontinued treatment, over half did so because the target Hb had been reached (M3: 55.6% [n = 74/133]; M6: 53.2% [n = 81/152]). Clinically significant adverse events (AEs) were observed in 9.9% of patients; the most common AE was infection (7.9%), while thrombotic events were only reported in 0.8% of patients. High baseline systolic blood pressure, high hematocrit levels at M3, and clinical improvement by M3 were identified as potential indicators of a positive response to an epoetin alfa biosimilar. Conclusion This subanalysis of the large ORHEO observational study has demonstrated the utility of biosimilar epoetin alfa in a real-world setting. Biosimilar epoetin alfa was seen to be efficacious and well tolerated in patients with breast cancer who presented with CIA, and no new safety signals were identified in this subpopulation. These data support the results observed in the parent ORHEO study, and confirm that biosimilar epoetin alfa (Hospira) is a therapeutic alternative for treating CIA in patients with breast cancer. Several potential prognostic indicators were identified that may warrant further study. Citation Format: Albrand H, Luporsi E, Michallet M, Soubeyran P. Usage of epoetin alfa biosimilars in the management of chemotherapy-induced anemia in patients with breast cancer: A subanalysis of the ORHEO study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-02.

Treatment of Chemotherapy-Induced Anemia Using Epoetin Alfa Biosimilar for Patients with Lymphoma and Myeloma: The Synergy Study

Background Recommendations on erythropoiesis-stimulating agents for the management of chemotherapy-induced anemia (CIA) are well established (Schrijvers D et al. Ann Oncol 2010;21[suppl 5]:v244-7). Iron supplementation can further improve treatment response of CIA, particularly in the case of iron deficiency (Pedrazzoli P et al. J Clin Oncol 2008;26:1619-25; Auerbach M et al. J Clin Oncol 2004;22:1301-7), but is under-used. Objective To evaluate the effect of epoetin alfa biosimilar, with or without iron, on CIA in current oncology and hematology practice. Methods SYNERGY was an observational, longitudinal, prospective, multicenter study conducted in France, from a representative, random sample of oncologists and hematologists. Patients of these clinicians were aged ≥18 years with solid tumors, lymphoma and/or myeloma and CIA, eligible for treatment with epoetin alfa biosimilar and followed for 12-16 weeks. A subanalysis of patients with lymphoma or multiple myeloma is presented here. Results Overall, 2167 patients were enrolled by 195 French oncologists and hematologists during June 2012-December 2014. Of these patients, 12.7% (n=264) had lymphoma and 6.6% (n=136) had multiple myeloma and were included in the analysis population, where the disease categories were non-exclusive; 84.5% (n=223) of patients with lymphoma were diagnosed with non-Hodgkin's lymphoma. Half of the patients with lymphoma and multiple myeloma were male. The majority of patients were ≥70 years old (60.6% of patients with lymphoma and 69.1% with multiple myeloma) and had a performance status of 0 or 1 (72.9% [n=180] of patients with lymphoma and 71.8% [n=94] with multiple myeloma). Baseline mean ± standard deviation (SD) hemoglobin (Hb) levels of patients with lymphoma and multiple myeloma were 9.5±0.8 g/dL and 9.5±0.9 g/dL; 40.2% (n=106) and 39.0% (n=53) of these patients had moderate anemia (Hb 8.0-9.5 g/dL), while 2.3% (n=6) and 4.4% (n=6) had severe or very severe anemia (Hb ≤8.0 g/dL), respectively. Iron status assessment was available for 60.2% (n=159) of patients with lymphoma and for 59.6% (n=81) with multiple myeloma. Concomitant iron supplementation was not prescribed with epoetin alfa biosimilar for the majority of patients. A total of 11.4% (n=30) of patients with lymphoma and 6.6% (n=9) of patients with multiple myeloma received iron, of whom 63.3% (n=19) and 77.8% (n=7) were prescribed oral iron formulations, respectively. Patients who reached their target Hb level (increase of ≥1 g/dL since enrollment or an increase of ≥2 g/dL, with no transfusions in the three previous weeks) was 79.1% (n=201) of patients with lymphoma and 84.6% (n=104) of patients with multiple myeloma, higher than the overall analyzed population (74.2%, n=1390). The response rate to epoetin alfa biosimilar (epoetin alfa biosimilar discontinued as Hb &gt; target level, with no transfusions in the three previous weeks) was lower in patients with lymphoma given iron supplementation versus those not given iron; 66.7% (n=20) of the iron supplementation group were responders, compared with 75.4% (n=169) of patients without iron. Response to epoetin alfa biosimilar was similar in patients with multiple myeloma regardless of the iron supplementation status (85.7% [n=6] of patients with iron supplementation and 81.0% [n=94] of patients without). The response to epoetin alfa biosimilar translated into an improvement in patient perception of fatigue (66.7% [n=20] of patients with iron supplementation and 72.5% [n=161] of patients without who had lymphoma; 71.4% [n=5] of patients with iron supplementation and 81.3% [n=91] of patients without who had multiple myeloma). Conclusions These results indicate that epoetin alfa biosimilar was effective in treating patients with CIA and lymphoma/myeloma in France and agrees with previous studies (Michallet M et al. BMC Cancer 2014;14:503). Iron supplementation did not appear to increase the response to epoetin alfa treatment in this population; however, confirmatory studies in larger patient cohorts are required. Disclosures Scotté: Hospira SAS: Research Funding. Laribi:Hospira SAS: Research Funding. Gisselbrecht:Hospira SAS: Research Funding; Roche: Consultancy, Research Funding; Baxter: Research Funding; Chugai Pharmaceutical: Research Funding; Bertram Glass: Research Funding. Spaeth:Hospira SAS: Research Funding. Kasdaghli:Hospira: Employment. Albrand:Hospira: Employment. Leutenegger:GECEM: Employment; Hospira SAS: Research Funding. Ray-Coquard:Hospira SAS: Research Funding; Amgen: Consultancy, Other: Paid instructor; PharmaMar: Consultancy, Other: Paid instructor; Roche: Consultancy, Other: Paid instructor.

Overview of French Routine Clinical Practice for the Management of Chemotherapy-Induced Anemia (CIA) with Biosimilar Epoetin Alfa in 563 Patients with Lymphoid Malignancies: A National Observational Study (The OncoBOS study)

▪Background. OncoBOS is a prospective, non-interventional study conducted in France to describe modalities of treatment with Binocrit® in routine clinical practice setting, for the correction of hemoglobin (Hb) in patients with CIA receiving chemotherapy (CT) for solid tumors, lymphoma or myeloma. This analysis focuses on patients with lymphoid malignancies (LM).Patients & methods. Patient ≥18 years old with LM, CIA and eligible for treatment with Binocrit® were included. This analysis reports patients characteristics along with anemia-related data such as Hb outcomes, Binocrit® treatment characteristics and concomitant treatments received, at baseline, 3-4 weeks and 12 (± 1) weeks later. Factors associated with a Hb increase ≥2 g/dL in patients with LM were analyzed by means of univariate and multivariate analyses.Results. 563 evaluable patients (302 males (53.6%), mean age 67.9 (SD 14.0) years were recruited from 34 sites, between September 2011 and July 2014. Non-Hodgkin lymphoma (NHL) (281 patients; 49.9%) and multiple myeloma (165 patients; 29.3%) were most prevalent. Among patients with NHL, 46.0% had a diffuse large B cell lymphoma, 11.5% a follicular lymphoma and 11.1% a mantle cell lymphoma. 62.5% of patients with NHL had a stage IV disease and bone marrow was involved by NHL in 45.2% of patients. A vast majority of patients (84.3%) suffering from multiple myeloma had a Durie-Salmon stage III myeloma. Mean baseline Hb was 9.5 (SD 1.0) g/dL, which increased by an average of 0.9 (SD 1.4) g/dL and 1.9 (SD 1.7) g/dL after 1 and 3 months, respectively. A Hb increase ≥1 g/dL was achieved by 51.3% of patients after 3-4 weeks of treatment with Binocrit®. About half of patients (53.0%) achieved a Hb increase ≥2 g/dL at week 12 (± 1). Patients received a mean Binocrit® dose of 31252.4 ± (SD 5815.9; median: 30000) UI once-weekly, over an average time span of 10.8 (SD 3.2; median: 13) weeks. Iron status (serum ferritin and transferrin saturation coefficient) was assessed in 29.1% of subjects at baseline. In total, 2.8% and 1.4% of patients concomitantly received oral or intravenous iron, respectively, during the follow-up period. 12.1% and 11.6% of patients received a folate supplementation at week 3-4 and 12, respectively. Moreover, 16.2% and 15.0% of patients received red blood cells transfusion over the 3-4 first weeks, and over the next 2 months, respectively. Over the treatment period, no treatment‐related adverse reaction was recorded. Factors negatively/positively associated with a Hb increase ≥2 g/dL (p<0.05) in the multivariate analysis were: prior radiotherapy [HR 0.16 (CI95% 0.04;0.64)]; history of venous thrombotic disease [HR 1.93 (1.14;3.28)]; administration of folate during the follow-up [HR 2.43 (1.69;3.49)]; a Hb level < 8 or [8;10[ g/dL at inclusion [HR 3.04 (1.97;4.69) and HR 1.62 (1.25;2.11), respectively]; 2 units of red blood cells received over the treatment period [HR 2.82 (1.91;4.16)].Conclusions. This study indicates that in real-life clinical conditions Binocrit® increases effectively Hb, without any adverse drug reaction, in anemic patients with lymphoid malignancies, whatever chemotherapy received. The effect of treatment with Binocrit® is rapid, with mean hemoglobin increase of 0.9 (SD1.4) g/dL seen as early as 3 or 4 weeks following the start of therapy. DisclosuresKarlin:Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. Metges:Sandoz: Consultancy. Khobta:Sandoz: Membership on an entity's Board of Directors or advisory committees. Boschetti:Sandoz: Membership on an entity's Board of Directors or advisory committees. Toledano:Sandoz: Membership on an entity's Board of Directors or advisory committees. Aubron-Olivier:Sandoz: Employment. Fernet:Sandoz: Employment. Fitoussi:Sandoz: Membership on an entity's Board of Directors or advisory committees.

N29 - Biosimilar epoetin alfa in the management of chemotherapy-induced aneamia: results from ANEMONE observational study

N29 - Biosimilar epoetin alfa in the management of chemotherapy-induced aneamia: results from ANEMONE observational study

1567 Overview of French routine clinical practice for the management of chemotherapy-induced anemia (CIA) with biosimilar epoetin alfa in 1298 patients with solid tumors: A national observational study (The OncoBOS study)

1567 Overview of French routine clinical practice for the management of chemotherapy-induced anemia (CIA) with biosimilar epoetin alfa in 1298 patients with solid tumors: A national observational study (The OncoBOS study)

State-of-the-art biosimilar erythropoietins in the management of renal anemia: lessons learned from Europe and implications for US nephrologists.

The European Medicines Agency (EMA), under a strictly regulated pathway, has approved several biosimilar products since 2005, including biosimilar versions of the erythropoiesis-stimulating agent (ESA) epoetin alfa since 2007. Subsequent to these approvals, the use of biosimilar epoetin alfa in the management of renal anemia has grown steadily throughout Europe. With the enactment of the US Biologics Price Competition and Innovation Act of 2009, a US Food and Drug Administration regulatory approval process for biosimilars was legalized. Thus, biosimilar erythropoietin products are expected to be available for prescription in the USA by mid-decade, presumably at a price that is competitive with the originator brand-name reference products. In this paper, we describe the status of originator and biosimilar ESAs, review the clinical development and regulatory approval of biosimilar erythropoietins in Europe, and summarize relevant efficacy and safety information of biosimilar erythropoietins in relation to their reference products to provide a background for US nephrologists as they appraise biosimilar erythropoietins as treatment options for renal anemia. Key lessons learned from Europe are that (a) EMA-approved biosimilar erythropoietins have comparable efficacy and safety profiles to their reference product erythropoietin; (b) pharmacovigilance preapproval and postapproval are critical, especially with regard to immunogenicity and vascular thromboembolic events; (c) strict preapproval and postapproval requirements must guide the regulatory pathway for biosimilars; and (d) high-quality manufacturing and production processes must be established to ensure quality biosimilar products. The availability of biosimilar erythropoietins in the USA will provide nephrologists with alternative effective, and potentially more affordable, treatment options for patients with renal anemia.

Management of chemotherapy‐induced anemia (CIA) with biosimilar epoetin alfa (Binocrit) in patients with pancreatic cancer (PC): An interim analysis of an ongoing French national observational study (The OncoBOS study).

479 Background: OncoBOS is a prospective, non-interventional study describing Binocrit use in routine practice in France in patients receiving chemotherapy treatment (CT) for solid tumors, lymphoma or myeloma. This interim sub-analysis focuses on patients with PC. Methods: Patients ≥18 years with PC, CIA and eligible for treatment with Binocrit were included in this analysis. Patients characteristics, data on CIA and its management and predominant factors considered by the physician in prescribing Binocrit were recorded at baseline (BL), 3-4 weeks and 12 (± 1) weeks later. Hemoglobin (Hb) outcomes assessed included the proportion of patients achieving a Hb increase ≥1 and ≥2 g/dL, and the mean Hb change from BL. Results: 59 patients with PC (32 females (54.2%), mean age 68.3 years) from 22 sites were recruited from September 2011 to April 2014. Mean and median BL Hb levels were both 10 g/dL. The mean increase in Hb level was 1.1 g/dL after 1 month and 1.2 g/dL after 3 months (p&lt;0.001 vs BL) of Binocrit treatment. A Hb increase ≥1 g/dL was achieved by 48.3% of patients at week 3-4 and 54.2% at week 12; a Hb increase ≥2 g/dL was achieved by 25.9% and 35.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit once weekly. Three of the 59 patients (5.1%) required a dose increase. Transfusion rates remained stable at 11.9% and 15.1% at week 3-4 and week 12, respectively. Oral and intravenous (IV) iron supplementation rates were low: oral iron was received by 1.7% and 0% of patients at week 3-4 and week 12, respectively; 20.3% and 13.2% of patients received IV supplementation at the same time points. Of note, iron status was assessed in only 11.9% of subjects at BL. Physicians considered quality of life (37.3%), fatigue (25.4%) and avoidance of blood transfusion (10.2%) as predominant factors in the rationale for CIA management. Over the treatment period, three treatment-related adverse reactions (non-serious) were recorded. Conclusions: This sub-analysis indicates that Binocrit, used in routine practice, is effective and well tolerated for the treatment of CIA in patients with PC.

Management of chemotherapy‐induced anemia (CIA) with biosimilar epoetin alfa (Binocrit) in patients with colorectal cancer (CC): An interim analysis of an ongoing French national observational study (The OncoBOS study).

742 Background: OncoBOS is a prospective, non-interventional study describing Binocrit use in routine practice in France in patients receiving chemotherapy treatment (CT) for solid tumors, lymphoma, or myeloma. This interim sub-analysis focuses on patients with CC, receiving usual chemotherapeutic agents. Methods: Patients ≥18 years with CC, CIA, and eligible for treatment with Binocrit were included in this analysis. Patients characteristics, data on CIA and its management, and predominant factors considered by the physician in prescribing Binocrit were recorded at baseline (BL), 3-4 weeks and 12 (±1) weeks later. Hemoglobin (Hb) outcomes assessed included the proportion of patients achieving a Hb increase ≥1 and ≥2 g/dL, and the mean Hb change from BL. Results: 96 patients with CC (51 males [53.1%], mean age 68.5 years) from 28 sites were recruited from September 2011 to April 2014. Mean and median BL Hb levels were 9.9 g/dL and 10 g/dL, respectively. The mean increase in Hb level was 1.2 g/dL after 1 month and 1.7 g/dL after 3 months (p&lt;0.001 vs. BL) of Binocrit treatment. A Hb increase ≥1 g/dL was achieved by 56.8% of patients at week 3-4 and 77.6% at week 12; a Hb increase ≥2 g/dL was achieved by 17.9% and 47.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit once weekly. Four of the 96 patients (4.2%) required a dose increase. Transfusion rates remained low at 2.1% and 1.1% at week 3-4 and week 12, respectively. Oral and intravenous (IV) iron supplementation rates were low: oral iron was received by 4.2% and 4.7% of patients at week 3-4 and week 12, respectively; 15.6% and 9.3% of patients received IV supplementation at the same time points. Physicians considered quality of life (49%), fatigue (24%), and avoidance of blood transfusion (15.6%) as predominant factors in the rationale for CIA management. Over the treatment period, no treatment-related adverse reaction was recorded. Conclusions: This sub-analysis indicates that Binocrit, used in routine practice, is effective and well tolerated for the treatment of CIA in patients with CC, whatever CT received.

Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients

Anemia is a frequent complication in patients with chronic kidney disease. However, human recombinant erythropoietin (rHu-EPO) has revolutionized the management of anemia in chronically dialyzed patients. Epomax ® is a new rHu-EPO alfa manufactured in Tunisia (Medis Laboratories). The aim of this study was to evaluate the efficacy and tolerance of Epomax ® in chronic hemodialysis (HD) patients in a phase-III, multicenter, clinical trial. Fiftythree HD patients (mean age 47.7 ± 13 years) who received a stable dose of rHu-EPO (Hemax ® , a rHu-EPO alfa manufactured by Biosidus Laboratories) subcutaneously were switched to Epomax ® via the same route of administration. At baseline, the mean systolic pressure was 132 ± 18 mm Hg and the mean diastolic pressure was 79 ± 8 mm Hg. The mean blood hemoglobin was 10.2 g/dL and the median ferritin level was 667 ng/mL. After a follow-up of 43 days, the mean blood hemoglobin was 10.5 g/dL under the effect of Epomax ® . There was no significant difference in the mean hemoglobin levels between the treatments with both drugs. Few adverse events were reported during the study. We conclude that Epomax ® was effective at maintaining the hemoglobin levels at target concentrations and was well tolerated in HD patients.