Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study

Background Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs. Aim This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy. Methods A retrospective cohort study was conducted during the years 2009-2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (ΔHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ΔHb≤0 g/dl), responders (0Delta;Hb≤2 g/dl), and highly responders (ΔHb>2 g/ dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID. Results Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in ΔHb as well as in frequency of non-responders, responders and highly responders among different types of ESAs were observed in both indications of use. Overall, around 15-20% of ESA users were non-responders. Strength of treatment, but no type of dispensed ESAs was found to be predictor of responsiveness to treatment. Conclusions No difference on the effects on hemoglobinemia among users of either biosimilars or reference product or ESAs covered by patent was observed in a general population from Northern Italy, despite a comparable dispensed dose of the different ESAs during the first three months of treatment

Epoetin Biosimilars in the Treatment of Chemotherapy-Induced Anemia: 10 Years' Experience Gained.

High-quality, safe, and effective biosimilars have the potential to increase access to biological therapies worldwide and to reduce cancer care costs. The European Medicines Agency (EMA) was the first regulatory authority to establish legislative procedures for the approval of biosimilars when they published their guidelines on similar biological medicinal products in 2005. Biosimilar epoetins were first approved in 2007, and a wealth of data has been collected over the last decade. Two biosimilar epoetins (under five commercial names) have been approved by the EMA so far. The availability of epoetin biosimilars generated discussion among the oncology community regarding prescribing these products, their efficacy, and their safety. These agents are approved only if they are shown in extensive analytical and clinical testing to have comparable quality, safety, and efficacy to the reference medicine, and real-world studies provide further data that biosimilar epoetins are an effective and well-tolerated option for the treatment of chemotherapy-induced anemia in patients with cancer. Other countries have adopted similar regulatory pathways to those in Europe and have approved epoetin biosimilars. The now extensive European experience with biosimilar epoetins should reassure regulators from other territories

Clinical Comparison of Renogen, a Biosimilar Epoetin-a, with the Originator, Eprex, in Chronic Kidney Disease Anemia in Indonesia: A Preliminary Study

Background: treatment of erythropoietin (EPO) is essential in chronic kidney disease (CKD) patients to maintain optimal hemoglobin (Hb) level. Renogen is a biosimilar epoetin-α, and Eprex is the originator epoetin-α. This study aimed to compare the efficacy and tolerance of Renogen with Eprex in CKD anemia. Methods: Renogen and Eprex were compared in a randomized (2:1), open-label study for 8 weeks, proceeded by 4 weeks adjustment (maintenance) phase, in anemic CKD patients undergoing HD in Cipto Mangunkusumo General Hospital, Jakarta, from June 2017 to October 2018. Results: a total of 45 patients (31 received biosimilar EPO and 14 received originator EPO) were included in the study.  At baseline, mean (SD) Hb levels were 10.9 (0.74) g/dL and 10.9 (0.61) g/dL in biosimilar and originator EPO groups, respectively. At end of study (8 weeks), mean (SD) Hb levels were 10.5 (1.28) g/dL and 11.0 (1.13) g/dL in biosimilar EPO and originator EPO groups, respectively.  The proportion of patients with Hb levels maintained within the target range (>10 g/dL) during 8 weeks randomization phase were 58.1% and 71.4% in biosimilar EPO and originator EPO, respectively (p=0.60; NS). There were no significant difference in epoetin dose between the 2 groups, and there was no drug-related adverse event in either group. Conclusion: Hb level at >10 g/dL could be maintained for 8 weeks of treatment with both originator and biosimilar EPO (more consistent with originator EPO and more fluctuations with biosimilar EPO), with similar epoetin dose and no drug-related adverse event

Effectiveness of pegylated erythropoietin in renal anaemia patients on dialysis-a multicentre, cross-sectional, observational outcome study

Background: Low dose of pegylated erythropoietin (PegEPO) is better than conventional erythropoietin stimulating agents (ESAs) in improving hyporesponsiveness and maintaining stable haemoglobin (Hb) levels in renal anaemic patients undergoing hemodialysis. This real-world study aimed to assess effectiveness and safety of low-dose PegEPO (30 µg/0.3 mL), administered at different time-points in renal anaemia patients on dialysis. Methods: HEMEPEG (HEMoglobin outcomE with PegEPO) was a multicentre, retrospective, cross-sectional, observational study of renal anaemia patients receiving PegEPO up to 3 months. The study assessed an increase in Hb, patients achieving Hb 10-12 g/dl, and Hb increase by ≥1 and ≥2 g/dl. Results: Data from 223 out of 273 patients from 19 Indian centers were analyzed. PegEPO was administered weekly to 132 patients (59.19%), with 38.64% being diabetic and 77.27% previously treated with ESAs. Ten day dosing was given to 91 patients (40.81%), including 46.15% diabetic patients and 72.53% previously treated with ESAs. A Significant (p<0.0001) increase in mean Hb levels from baseline to day 30, 60 and 90 were observed for both studied groups, with a target Hb of 10-12 g/dl achieved in 51.08% and 52.85% of patients in the respective groups after 3 months. An increase in Hb by ≥1 and ≥2 g/dl were observed in weekly (68.67% and 45.78%) and 10-day group (77.14% and 50.00%) patients, respectively. Conclusions: PegEPO (30 µg/0.3 mL) was effective treatment of renal anaemia and diabetic chronic kidney disease (CKD) patients on dialysis when administered weekly or every 10 days over a 3-month treatment period