The Impact of Biosimilar Use on Total Cost of Care and Provider Financial Performance in the Medicare Oncology Care Model: A Population-Based Simulation Study.

INTRODUCTION: Payment for oncology care is increasingly moving from fee-for-service to value-based payment (VBP). VBPs are agreements in which providers are held accountable for total cost of care (TCOC) through risk-sharing arrangements with payers that tie reimbursement levels to TCOC benchmarks. Oncology biosimilars may play an important role in managing financial risk in the VBPs like Medicare's Oncology Care Model (OCM), but there has been limited research in this area. The objective of this study is to estimate the impact of biosimilar adoption on TCOC and oncology provider financial performance under the terms of the Medicare OCM. METHODS: We conducted a population-based simulation study using the Medicare Limited Data Set (LDS) and the methodology of Medicare's OCM. The primary outcome was the simulated average change in TCOC per 6-month episode of care attributable to use of biosimilars as an alternative to reference products. The study population consisted of episodes of care in 2020 and using the reference product or corresponding biosimilar for bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, or pegfilgrastim. TCOC was calculated for each episode of care with use of reference products only and compared with TCOC with corresponding biosimilars. The simulation calculated TCOC outcomes in cohorts of 100 episodes sampled from the Medicare LDS study population using a Monte Carlo simulation with 10,000 iterations. RESULTS: Among the total of 8281 6-month oncology care episodes identified in the study period (initiating January 2020 to July 2020) in Medicare claims, 1586 (19.2%) episodes met OCM and study criteria and were included. Applying the simulation methods to these observed episodes, biosimilar substitution reduced mean TCOC per episode by $1193 (95% CI $583-1840). The cost reduction from biosimilars represented 2.4% of the average TCOC benchmark and led to a 15% reduction in the risk of providers needing to pay recoupments to Medicare for exceeding TCOC benchmarks. CONCLUSIONS: On the basis of our simulation study using observed Medicare claims and OCM criteria, we found that biosimilar substitution for reference products can significantly lower episode TCOC and improve provider financial performance under the terms of the largest value-based payment model implemented to date.

An observational study of an adjusted patient blood management protocol intended to lower rates of transfusion following total knee arthroplasty in patients with preoperative anemia.

BACKGROUND: Patients with preoperative anemia have a higher risk of requiring blood transfusion after major orthopedic surgery due to increased blood loss and closer transfusion thresholds. Various patient blood management (PBM) policies aim to reduce transfusion rates. This observational study aimed to investigate blood loss and evaluate the effectiveness of an adjusted surgical PBM protocol in patients with anemic chronic disease (ACD) undergoing elective total knee arthroplasty (TKA). METHODS: A consecutive cohort of patients underwent elective unilateral TKA with an adjusted PBM protocol. The protocol consisted of epoetin (EPO) alfa therapy prescribed by the surgeon, routine administration of tranexamic acid (TXA), and standardized postoperative pharmacologic prophylaxis for thromboembolism. The performance of this PBM protocol was analyzed in patients with a baseline hemoglobin level of less than 12 g/dl. Hemoglobin levels were controlled at admission, on postoperative day (POD) 1, and on POD 7 ± 1. A bleeding index (BI-7) was used as an estimate of blood loss up until POD 7. Multiple linear regression was used to assess whether there were any differences in BI-7 between ACD- and ACD + patients. RESULTS: A total of 751 patients with complete hemoglobin monitoring were included in the study. Of these patients, 68 (9.1%) had a baseline hemoglobin concentration of less than 12 g/dl (ACD group). In this group, 28 patients (41.2%) received preoperative EPO therapy. The mean adjusted BI-7 for the study population was 3.0 (95% CI, 2.9 to 3.0) g/dl in the ACD- group and 2.3 (95% CI, 2.0-2.6) g/dl in the ACD + group. The difference in BI-7 was statistically significant (difference, 0.6 [95% CI: 0.3 to 0.9] g/dl, p < 0.001). No major complications occurred in the ACD + group, whereas there were three complications in the ACD- group (p = 1.00). CONCLUSIONS: ACD patients undergoing TKA did not have an increased risk of bleeding or bleeding complications with the use of the adjusted PBM protocol. None of ACD patients required transfusion. ACD patients undergoing TKA experienced significantly less blood loss than patients with no preoperative anemia with the use of the adjusted PBM. We now consider the use of EPO in ACD patients with no nutritional deficiencies undergoing TKA at a baseline hemoglobin level of 11 g/dl. However, this should be validated in larger cohorts with a higher prevalence of ACD patients.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

Long-Term Efficacy of Erythropoiesis-Stimulating Agents in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Multicenter Real-Life Data

Objective: This study was undertaken to evaluate the long-term clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndrome (MDS) in a real-life setting. Materials and Methods: A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion needs were recorded before treatment and at 12 months, 24 months, 36 months, and 48 months of treatment. Results: At the 36-month (p=0.025) and 48-month (p=0.022) visits, epoetin alfa yielded significantly higher hemoglobin levels compared to darbepoetin alfa. Transfusion needs were also significantly lower with epoetin alfa compared to darbepoetin alfa at 24 months (p=0.012) and in the low-risk group compared to the intermediate-risk group at 24 months (p=0.018), 36 months (p=0.025), and 48 months (p<0.001). Treatment response rates at the 24-month, 36-month, and 48-month visits in the epoetin alfa (43.0%, 33.6%, and 27.1%), darbepoetin alfa (29.9%, 22.7%, and 16.5%), low-risk (39.3%, 30.0%, and 26.0%), and intermediate-risk (29.6%, 24.1%, and 11.1%) groups were lower than those obtained at 12 months, and the values differed significantly for the 36-month and 48-month visits with values ranging from p<0.05 to p<0.001. Conclusion: This real-life long-term ESA extension study investigated the clinical efficacy of epoetin alfa and darbepoetin alfa for up to 48 months, revealing that treatment efficacy reached a plateau starting from the 24th month of therapy with a continuing decrease in treatment response rates regardless of treatment type, risk status, or gender. Nonetheless, significantly higher hemoglobin levels and marked improvement in transfusion needs were evident in epoetin-treated patients compared to darbepoetin-treated patients and in the low-risk group compared to the intermediate-risk group.

Pharmacist-driven epoetin alfa-epbx dosing for hospitalized patients.

PURPOSE: To determine the effectiveness of pharmacy consultation in managing epoetin alfa-epbx dosing for inpatients on hemodialysis. METHODS: This multisite, retrospective cohort study evaluated the implementation of an initial dose consultation for epoetin alfa-epbx by pharmacists. A pre-post cohort study evaluated patients from August 2020 through January 2021 and August 2021 through January 2022, respectively. Hospitalized patients were included if they were at least 18 years of age, received hemodialysis, and were administered an erythropoiesis-stimulating agent (ESA) for anemia due to chronic kidney disease. Patients were excluded for religious objections to receiving blood products or if patients were discharged or died before their first hemodialysis session. The primary outcome was the average epoetin alfa-epbx acquisition cost per patient. Secondary endpoints were the epoetin alfa-epbx overall pharmacy purchasing cost, the average dose, and the number of administered doses. A subgroup analysis was performed for patients in the post group with an outpatient ESA before admission to determine the epoetin alfa-epbx days saved. RESULTS: A total of 264 patients were included in the pre group, and 272 patients were included in the post group. The average acquisition cost was significantly lower in the post group ($1,681.77 vs $1,041.35, P < 0.0001). The overall pharmacy purchasing cost was also lower in the post group ($148,970.89 vs $127,873.25). The post group had a significantly lower average dose (13,694 vs 10,112 units, P = 0.0004), while the number of administered doses did not differ significantly between the groups (2.09 vs 1.79 doses, P = 0.0668). The subgroup analysis included 83 patients, which yielded 53 epoetin alfa-epbx days saved. CONCLUSION: Pharmacist-driven ESA dosing was associated with significant decreases in ESA average acquisition cost and average total dose per patient.

Pharmacokinetic and pharmacodynamic study of three products of epoetin alfa as single subcutaneous dose in healthy volunteers.

Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980s and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40 000 IU of Eprex/Erypo® and Hemax® PFS. This clinical trial was conceived following an open-label, randomized, three-way three-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. To analyze similarity between Hemax® PFS and the innovator product, Eprex®, area under the curve (AUC) and Cmax of both products have been compared. The 90% CI lower limit for the geometric mean ratios was higher than 80% for any comparisons, and the 90% CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. The comparison between Hemax® PFS and Eprex® resulted in similar 90% CI for Cmax , AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent, and elimination (with an elimination half-life close to 25-30 h for each formulation).

Epoetin alfa biosimilar (HX575): A review of 15 years' post-approval clinical experience.

Biosimilars offer the potential to expand patient access and reduce healthcare costs. Therefore, it is of importance that clinicians and patients are reassured about their efficacy and safety in practice. In 2007, Binocrit® (HX575; Sandoz GmbH, Kundl, Austria) was the first epoetin alfa biosimilar approved for use in chemotherapy induced anaemia (CIA), chronic renal failure (CRF), and more recently myelodysplastic (MDS) anaemia. Since its approval, there has been a plethora of data demonstrating the well-tolerated safety profile of HX575. This review will outline the safety results collected from key studies that have added to the extensive HX575 (Binocrit® unless otherwise stated) clinical experience. With a focus on all approved indications, we will review the safety data collected across a range of study types, to further consolidate the reassurance for the use of HX575 in these indications.

Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial.

Background: This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. Method: This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results: Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. Conclusion: The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

The Clinical Efficacy of Epoetin Alfa and Darbepoetin Alfa in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Retrospective Multi-center Real-Life Study.

This study aimed to evaluate the clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndromes (MDS) in the real-life setting. A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion need were recorded before and during 12-month treatment. Hemoglobin levels were significantly higher at each follow up visit when compared to baseline levels in both epoetin alfa (mean ± SD 8.68 ± 1.0 g/dL at baseline vs. 9.83 ± 1.45, 9.99 ± 1.55, 10.24 ± 1.77 and 10.2 ± 1.5 g/dL, respectively) and darbepoetin alfa (8.83 ± 1.09 g/dL at baseline vs. 9.62 ± 1.37, 9.78 ± 1.49, 9.9 ± 1.39 and 10.1 ± 1.5 g/dL, respectively) groups (p < 0.001 for each). Transfusion need significantly decreased from baseline at each study visit in the epoetin alfa group (p < 0.001) and only at the 12th month visit (p < 0.001) in the darbepoetin alfa group. Hemoglobin levels or transfusion need was similar between treatment groups. Overall, 12-month response rate was 58.1% for epoetin alfa and 41.9% for darbepoetin alfa, with no significant difference between treatment groups, whereas higher response rate was noted within the first three months (62.7%) compared to next 9 months (ranged 44.4-60%) of treatment in the epoetin alfa group (p ranged 0.002 to < 0.001). This real-life retrospective study revealed similar efficacy of epoetin alfa and darbepoetin alfa among low risk or intermediate-1 risk MDS patients with no difference in treatment response between treatment groups, whereas a likelihood of earlier treatment response in the epoetin alfa group. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01458-1.