https://orcid.org/0000-0002-9430-4675
Abstract
Aims
Therapeutic guidelines recommend prophylaxis against chemotherapy-induced (febrile) neutropenia (CIN/FN). Pegfilgrastim (Neulasta), biosimilar pegfilgrastim-jmdb (Fulphila), and pegfilgrastim with on-body injector (OBI; Neulasta Onpro) are options for CIN/FN prophylaxis. We aimed to simulate the cost-savings and budget-neutral expanded access to CIN/FN prophylaxis or anticancer treatment achieved through conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and to evaluate the economic impact of FN-related hospitalization costs due to pegfilgrastim-OBI failure.
Methods
Cost-savings from conversion from pegfilgrastim-OBI to biosimilar pegfilgrastim-jmdb were simulated in a panel of 15,000 patients with cancer from the US payer perspective. The primary analyses included conversion rates of 10% to 100%. Adjusted analyses also considered OBI device failure rates of 1% to 7% and associated costs of FN-related hospitalization. Simulations of budget-neutral expanded access to prophylaxis with pegfilgrastim-jmdb or to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for diffuse large B-cell lymphoma (DLBCL) were also performed.
Results
In a 15,000-patient panel, conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb resulted in cost-savings ranging from $481,259 (10% conversion) to $4,812,585 (100% conversion) in a single cycle. Over 6 cycles at 100% conversion, savings were $28,857,510 and could provide 9,191 additional doses of pegfilgrastim-jmdb or 4,463 cycles of R-CHOP to patients with DLBCL. Adjusted for OBI failure, cost-savings over 6 cycles ranged from $2,935,565 (10% conversion; pegfilgrastim-OBI failure rate of 1%) to $32,236,499 (100% conversion; 7% failure). These cost-savings could provide 943 doses of pegfilgrastim-jmdb or 454 doses of R-CHOP (10% conversion; 1% pegfilgrastim-OBI failure) or provide 10,261 doses of pegfilgrastim-jmdb or 4,982 cycles of R-CHOP (100% conversion; 7% failure).
Conclusion
Conversion from pegfilgrastim to pegfilgrastim-jmdb is associated with significant cost-savings which increase markedly when also accounting for pegfilgrastim-OBI failure and associated FN-related hospitalizations. These general and failure-related cost-savings could be allocated on a budget-neutral basis to provide more patients with additional CIN/FN prophylaxis or antineoplastic treatment.
Introduction
Chemotherapy-induced neutropenia and febrile neutropenia (CIN/FN) are potentially life-threatening complications of myelosuppressive therapyCitation1,Citation2. FN is a major dose-limiting toxicity of chemotherapy and is associated with increased hospitalizations and mortality riskCitation3–5. Many studies have demonstrated that the prophylactic use of granulocyte colony-stimulating factor (G-CSF) reduces the risk, duration, and severity of FN and subsequently reduces infections and related hospitalizations by stimulating the production and maturation of neutrophils in bone marrowCitation3–5. Recent evidence from real-world studies confirmed the benefit of G-CSF prophylaxis in reducing FN-related treatment disruption and the length of FN-related hospitalization. For instance, in patients with indolent non-Hodgkin lymphoma, primary prophylaxis with pegfilgrastim in an outpatient setting reduced treatment disruption to 1.6% compared with 11.4% in the control groupCitation6,Citation7. Moreover, FN related hospitalization was significantly shorter among patients who received pegfilgrastim. Furthermore, prophylactic pegfilgrastim was confirmed to be equally effective to filgrastimCitation8.
According to the National Comprehensive Cancer Network (NCCN) and the European Organization for Research and Treatment of Cancer guidelines, G-CSF use is recommended as primary prophylaxis of CIN when the overall risk for FN for the treatment regimen is ≥20%. Prophylaxis with G-CSF should begin with the first cycle of treatment, the need for prophylaxis should be assessed at the start of each subsequent cycle, and, as necessary, continue throughout all cyclesCitation2,Citation9. Patients treated with myelotoxic chemotherapy regimens with an FN risk between 10% and 20% and with such risk factors as age ≥65 years, advanced disease condition, prior FN incidence, and renal and/or cardiovascular disease are also recommended to receive prophylactic G-CSF. CIN/FN prophylaxis is not recommended for chemotherapy regimens with an FN risk <10%. During the COVID-19 pandemic, the NCCN issued a short-term recommendation to use G-CSF regimens for high-risk (>20%) or intermediate-risk patients with FN risk of 10% to 20%, even in the absence of risk factorsCitation10. In addition, to reduce the risk for contracting COVID-19 by making frequent trips to the outpatient treatment center, the NCCN recommends patients may consider self-administration of daily filgrastim or the use of long-term pegfilgrastim prophylaxisCitation10.
CIN/FN prophylaxis with pegfilgrastim is recommended to be administered between 24 and 72 h after receiving the chemotherapy treatment, which requires patients to return to the oncology clinic the day after chemotherapyCitation2. However, real-world data indicate that same-day administration of short-term and long-term G-CSF prophylaxis is becoming increasingly commonCitation11,Citation12. In 2015, an on-body injector (OBI) device (Neulasta Onpro; Amgen, Thousand Oaks, CA, USA) was approved by the US Food and Drug Administration (FDA)Citation13. This device is applied on the same day of chemotherapy treatment and delivers pegfilgrastim approximately 27 h laterCitation11. Several studies have demonstrated that the pegfilgrastim-OBI device is subject to failure at a rate of 1% to 6.9%Citation14–17. Because pegfilgrastim-OBI is a single-administration formulation, a missed or partial dose resulting from device failure may significantly increase the risk for FN and FN-related hospitalizations.
Biosimilars are comparable but nonidentical versions of approved biological agents with similar physicochemical properties, efficacy, and safety profiles to an approved reference product. Several pegfilgrastim biosimilars have been developed. The biosimilar pegfilgrastim-jmdb (Fulphila; Viatris, Canonsburg, PA, USA) was approved by the FDA in 2018 as the first biosimilar to pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA, USA)Citation18. In a randomized, double-blind, parallel-group phase 3 trial, pegfilgrastim-jmdb was found to have equivalent efficacy and a comparable safety profile to reference pegfilgrastim in patients with breast cancer eligible to receive chemotherapy treatmentCitation19. The duration of severe neutropenia among patients who received pegfilgrastim-jmdb and reference pegfilgrastim was within the prespecified equivalence range of ±1 day. Moreover, post hoc analysis demonstrated that pegfilgrastim-jmdb is noninferior to reference pegfilgrastim in terms of FN incidence, assuming a noninferiority margin of 9%. In addition, a total of 806 treatment-emergent adverse events (TEAEs) were reported in 114 (90%) patients who received pegfilgrastim-jmdb, and 414 TEAEs were reported in 58 (87%) patients receiving reference pegfilgrastim, which confirmed that biosimilar pegfilgrastim-jmdb has a comparable safety profile to reference pegfilgrastimCitation19.
Previous pharmacoeconomic studies in Europe and the United States have demonstrated that the use of biosimilar G-CSF provides significant cost-savings that can be used to expand access to additional CIN/FN prophylaxis or expensive anticancer treatments on a budget-neutral basisCitation20–26. Three studies are particularly relevant to the results reported herein, because they either estimated savings and expanded access from conversion from reference to biosimilar pegfilgrastim, or they considered the savings and access from conversion from pegfilgrastim-OBI to the biosimilar standard filgrastim under consideration of OBI device failure rates, the ensuing loss of prophylaxis, the increased risk for FN, and the incremental costs of FN-related hospitalizationCitation20,Citation21,Citation25. An ex ante simulation of conversion from reference pegfilgrastim to pegfilgrastim-bmez utilizing average sale price (ASP) and a post facto simulation utilizing wholesale acquisition cost (WAC) demonstrated the budget-neutral value of biosimilar conversion in a hypothetical panel of 20,000 patientsCitation25. Similarly, a simulation using ASP, WAC, and an age-proportionate blended ASP/WAC documented how savings accrued from conversion from reference pegfilgrastim (prefilled syringe or OBI) to pegfilgrastim-cbqv in a panel of 20,000 patients would allow the purchase of 9,709 to 58,253 additional doses of pegfilgrastim-cbqv—enough to provide prophylaxis to 1,618 to 9,708 patients for 6 cycles of myelotoxic chemotherapy on a budget-neutral basisCitation21. A third study, focused on conversion from prophylaxis with the pegfilgrastim-OBI device to biosimilar standard filgrastim-sndz, also considered the incremental costs associated with 1% to 10% failure rates of the OBI device, the associated loss of prophylaxis, and the increased risk for FN and FN-related hospitalizationCitation20. Despite the need for daily injections, conversion to biosimilar filgrastim provided marked cost-savings and afforded significant expanded access.
Building upon our prior simulation studies and extending into conversion to biosimilar pegfilgrastim-jmdb, the first objective of this present simulation was to evaluate the cost-savings that could be generated in a panel of 15,000 patients at risk for CIN/FN because of myelosuppressive therapy, by converting from pegfilgrastim-OBI to prophylaxis with biosimilar pegfilgrastim-jmdb without considering pegfilgrastim-OBI device failure. Based on these cost-savings, we simulated the budget-neutral expanded access to additional prophylaxis with pegfilgrastim-jmdb or additional anticancer treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the setting of diffuse large B-cell lymphoma. The second objective was to evaluate, in similar-sized panels, the cost-savings from biosimilar conversion to pegfilgrastim-jmdb under consideration of OBI device failure rates and the associated FN-related hospitalization costs, as well as the expanded access to additional prophylaxis or R-CHOP treatment.
Methods
Model
For this economic analysis, a simulation model was developed from the US payer perspective for a hypothetical panel of 15,000 patients at risk for CIN/FN. The model examined several scenarios, including the administration of 1 to 6 cycles of prophylaxis; conversion rates from pegfilgrastim-OBI to biosimilar pegfilgrastim-jmdb ranging from 10% to 100%; and pegfilgrastim-OBI failure rates of 1% to 7%.
Assumptions
The following assumptions were considered in the cost-simulation analyses:
The cost simulation and expanded access models are for the United States, and are expressed in 2020 US dollars.
The efficacy and safety of all G-CSF treatments were considered to be equal. Studies have demonstrated that pegfilgrastim-jmdb has an equivalent clinical efficacy and safety profile when compared with reference pegfilgrastimCitation19.
Pegfilgrastim-OBI device failure was considered equivalent to lack of prophylaxis.
The cost simulation is from the payer’s perspective.
The models considered only the costs of medications and administration (facility/hospital outpatient), as well as the cost of FN-related hospitalizations. Considering the payer’s perspective, excluded from the models were patient-related direct and indirect costs, such as co-pays, travel, meals, and time, among others, as well as any residual patient-related costs associated with the management of FN and/or chemotherapy dose reductions, delays, or cancelations. Excluded also were any clinic visit costs, as these visits were assumed to be part of routine care. In addition, drug discounts or rebates above and beyond those considered in the ASP were not considered.
This analysis did not account for cost of visit or patient’s copays, other patient-related costs, such as travel, meals, time, or other costs associated with the management of FN and/or chemotherapy dose reductions, delays, or cancelations. In addition, drug discounts or rebates above and beyond those included in the ASP were not considered.
The R-CHOP regimen was modeled based on a body surface area of 1.8 m2.
Differential base rate of FN hospitalization (FN-HOSP) in non-Hodgkin lymphoma (NHL; rate of FN-HOSP without colony-stimulating factor [CSF] minus rate with CSF) was 10.03% over a 6-cycle regimen (13.25% with CSF, 23.28% without CSF) with 56% occurring in Cycle 1Citation27.
Cost inputs
Cost inputs used in this analysis included medication costs, costs for medication administration, and FN-related hospitalization costs.
Cost of medications were based on second-quarter 2020 ASP for pegfilgrastim-OBI, pegfilgrastim-jmdb, and R-CHOP drugs extrapolated from the Centers for Medicare & Medicaid Services (CMS) October 2020 Medicare Part B Drug Payment LimitsCitation28 as follows:
Reference drug’s ASP = payment limit of reference drug – 6% add-on of reference (adjusted for sequestration)
Biosimilar’s ASP = payment limit of biosimilar – 6% add-on of reference (adjusted for sequestration)
Pegfilgrastim-jmdb (6 mg) cost: $3,081.24
Pegfilgrastim-OBI (6 mg) cost: $3,424.43
R-CHOP regimen (1 cycle) cost: $6,470.66.
The costs for medication administration of pegfilgrastim-OBI and pegfilgrastim-jmdb administration were based on the 2020 CMS Outpatient Prospective Payment SystemCitation29:
The cost of therapeutic, prophylactic, or diagnostic injection, subcutaneous or intramuscular (Healthcare Common Procedure Coding System [HCPCS; code 96372]: $60.46
The cost of application on-body injector (HCPCS code 96377): $38.11.
FN-related hospitalization costs in the United States in 2012 of $25,676 per episode for patients with NHLCitation30 were adjusted per the Consumer Price Index for Medical Care to $31,913.68 for 2020Citation31.
Analyses for the 15,000-patient panel
Cost-savings were simulated for assured prophylaxis with biosimilar pegfilgrastim-jmdb over pegfilgrastim-OBI by first taking the per-patient difference in treatment cost over 1 to 6 cycles and then extrapolating to a 15,000-patient panel across conversion rates ranging from 10% to 100% (“unadjusted savings”). Panel savings were then adjusted for device failure rates ranging from 1% to 7% based upon the estimated rate of FN-related hospitalization associated with device failure and FN-related hospitalization costs (“adjusted savings”). Based on both the adjusted and unadjusted cost-savings, the number-needed-to-convert (NNC) to purchase 1 additional dose of biosimilar pegfilgrastim-jmdb or R-CHOP was then estimated. The NNC was calculated as the ratio of the cost of treatment (1 cycle of either biosimilar pegfilgrastim-jmdb or R-CHOP) to the potential cost-savings generated by converting from reference pegfilgrastim to biosimilar pegfilgrastim-jmdb. Finally, expanded access to pegfilgrastim-jmdb and R-CHOP was modeled using both adjusted and unadjusted cost-savings to determine the number of single doses that could be purchased or the number of regimens that could be provided on a budget-neutral basis.
Results
Medication and administration costs and cost-savings per patient from conversion to pegfilgrastim-jmdb
The per-patient cost of pegfilgrastim-jmdb ranged from $3,141.70 (1 cycle of prophylaxis) to $18,850.21 (6 cycles of prophylaxis). The per-patient cost of pegfilgrastim-OBI ranged from $3,462.54 (1 cycle of prophylaxis) to $20,775.24 (6 cycles of prophylaxis). Conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb resulted in cost-savings per patient that ranged from $320.84 (1 cycle of prophylaxis) to $1,925.03 (6 cycles of prophylaxis; )
Table 1. Medication and administration costs and cost-savings per patient from conversion to pegfilgrastim-jmdb.
Unadjusted cost-savings and expanded access to prophylaxis with pegfilgrastim-jmdb and treatment with R-CHOP
In a panel of 15,000 patients, total savings ranged between $481,259 for a 10% conversion rate in 1 treatment cycle and $28,875,510 for a 100% conversion rate across 6 cycles (). In 1 cycle of chemotherapy, the number of additional patients who could receive assured prophylaxis with pegfilgrastim-jmdb on a budget-neutral basis by reallocating savings ranged from 153 patients at a 10% conversion rate to 1,532 patients at a 100% conversion rate (). Over 6 treatment cycles, a 10% conversion rate provides the opportunity to purchase 919 additional doses of pegfilgrastim-jmdb. At a 100% conversion rate over 6 cycles, a total of 9,191 additional doses of pegfilgrastim-jmdb can be purchased and used to treat 1,532 additional patients for 6 cycles. The NNC to purchase 1 additional dose of pegfilgrastim-jmdb was 9.79 patients converted for 1 cycle of prophylaxis and 1.63 converted for 6 cycles of prophylaxis.
Table 2. Cost-savings and expanded access to prophylaxis with pegfilgrastim-jmdb and treatment with R-CHOP from conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb in a panel of 15,000 cancer patients at risk for CIN/FN.
If the cost-savings were reallocated to provide additional doses of the agents in the R-CHOP regimen, 74 additional cycles of R-CHOP could be purchased if 10% of patients were converted for 1 treatment cycle, increasing to 446 cycles with conversion over 6 cycles (). At a 100% conversion rate over 6 cycles, 4,463 additional cycles of R-CHOP could be purchased. This translates to 74 additional patients who could be provided with a 6-cycle regimen of R-CHOP at 10% conversion and 744 patients at 100% conversion on a budget-neutral basis. The NNC to purchase 1 additional dose of R-CHOP was 20.17 patients converted for 1 cycle of treatment and 3.36 converted for 6 cycles.
Pegfilgrastim-OBI failure and FN-related hospitalizations in a panel of 15,000 patients with cancer at risk for CIN/FN
Based on pegfilgrastim-OBI failure rates of 1% to 7%, the number of patients with pegfilgrastim-OBI failure in the 15,000-patient panel ranged from 150 to 1,050 (). Over 6 cyles of R-CHOP, the estimated number with FN-related hospitalizations ranged from 15.05 to 105.32, respectively. The FN-related hospitalization costs in a panel of 15,000 patients ranged from $480,141 (at 1% failure rate) to $3,360,989 (at 7% failure rate).
Table 3. Pegfilgrastim-OBI failure in a panel of 15,000 patients with cancer treated with 6 cycles of R-CHOP and at risk for CIN/FN.
Cost-savings and expanded access adjusted for OBI device failure and FN hospitalization
Adjusted cost-savings for 1 cycle of chemotherapy
Adjusting for pegfilgrastim-OBI failure and the risk for FN and FN-related hospitalization, cost-savings in the first cycle of prophylaxis from conversion to pegfilgrastim-jmdb in a panel of 15,000 patients ranged from $508,146 (at 10% conversion and pegfilgrastim-OBI failure rate of 1%) to $6,694,739 (at 100% conversion and 7% failure rate; ).
Table 4. Cost-savings of prophylaxis for 1 treatment cycle from conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and expanded access to prophylaxis with pegfilgrastim-jmdb or treatment with R-CHOP in a panel of 15,000 patients with cancer at risk for CIN/FN adjusted for pegfilgrastim-OBI failure.
Adjusting for FN-HOSP costs associated with pegfilgrastim-OBI failure, the cost-savings from conversion to pegfilgrastim-jmdb could provide a total of 162 additional doses of biosimilar pegfilgrastim-jmdb or 79 additional doses of R-CHOP at 10% conversion and 1% pegfilgrastim-OBI failure rate. At a 100% conversion and 7% device failure rate, the cost-savings could provide 2,131 additional doses of pegfilgrastim-jmdb or 1,035 additional doses of R-CHOP ().
The NNC to purchase 1 additional dose of pegfilgrastim-jmdb when converting from pegfilgrastim-OBI to pegfilgrastim-jmdb was 9.27 at a device failure rate of 1% and declined to 7.04 at a device failure rate of 7% (). The NNC to purchase 1 additional dose of R-CHOP ranged from 19.10 at a failure rate of 1% to 14.50 at a failure rate of 7% ().
Adjusted cost-savings for 6 cycles of chemotherapy
Adjusting for FN-HOSP costs associated with pegfilgrastim-OBI failure, cost-savings over 6 cycles of prophylaxis from conversion to pegfilgrastim-jmdb in a panel of 15,000 patients ranged from $2,935,565 (at 10% conversion and pegfilgrastim-OBI failure rate of 1%) to $32,236,499 (at 100% conversion and 7% failure rate; ).
Table 5. Cost-savings over 6 cycles from conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and expanded access to prophylaxis with pegfilgrastim-jmdb or treatment with R-CHOP in a panel of 15,000 patients with cancer at risk for CIN/FN adjusted for pegfilgrastim-OBI failure.
Adjusting for FN-HOSP costs associated with pegfilgrastim-OBI failure, the cost-savings from conversion to pegfilgrastim-jmdb could provide a total of 934 additional doses of biosimilar pegfilgrastim-jmdb or 454 additional doses of R-CHOP at 10% conversion and 1% PEG-OBI failure rate. At a 100% conversion and 7% device failure rate, the cost-savings could provide 10,261 additional doses of pegfilgrastim-jmdb or 4,982 additional doses of R-CHOP ().
The NNC to purchase 1 additional dose of pegfilgrastim-jmdb was 1.61 at a device failure rate of 1% and declined to 1.46 when at a failure rate of 7% (). The NNC to purchase 1 additional dose of R-CHOP ranged from 3.31 at a failure rate of 1% to 3.01 at a rate of 7% ().
Discussion
In this study, economic simulation modeling was performed to estimate the cost-efficiency of biosimilar pegfilgrastim-jmdb relative to reference pegfilgrastim-OBI with and without taking into consideration the impact of FN-related hospitalization costs resulting from OBI device failure. Our findings demonstrate that the cost-savings (unadjusted for OBI device failure) from conversion to pegfilgrastim-jmdb in a panel of 15,000 patients at risk for CIN/FN risk ranged from ∼$481,000 at 10% conversion rate for 1 cycle of prophylaxis to ∼$29 million at 100% conversion rate for 6 cycles of prophylaxis. When pegfilgrastim-OBI device failure rate was taken into consideration, the estimated cost-savings over 6 cycles ranged from ∼$3 million at 10% conversion rate and 1% OBI failure rate to more than ∼$32 million at 100% conversion and 7% OBI failure rate.
Further, our results show that when these cost-savings were allocated to purchase additional doses of biosimilar pegfilgrastim-jmdb or R-CHOP anticancer treatment, significant numbers of patients could be provided with prophylaxis or treated on a budget-neutral basis. Without taking pegfilgrastim-OBI device failure into consideration, conversion of 10% of the panel for 1 cycle could provide approximately 150 additional patients with pegfilgrastim-jmdb, whereas more than 9,000 additional patients could be treated at 100% conversion rate over 6 treatment cycles. Moreover, between 74 (10% conversion rate, 1 cycle of treatment) and ∼4,500 additional patients (100% conversion rate, 6 cycles of prophylaxis) could receive R-CHOP treatment on a budget-neutral basis.
Additionally, by accounting for pegfilgrastim-OBI device failure, the number of patients who could gain access to additional prophylaxis with biosimilar pegfilgrastim-jmdb or additional treatment with R-CHOP on a budget-neutral basis could increase by up to 14% and 7%, respectively, depending on device failure rates of 1% to 7% (100% conversion rate over 1 cycle of treatment). Through conversion of a 15,000-patient panel over 6 cycles of treatment, the number of patients who could receive an entire 6-cycle regimen of prophylaxis or anticancer treatment with R-CHOP on a budget-neutral bases could increase by 11% and 5%, respectively (100% conversion and 7% device failure rate). Thus, our economic simulation further confirms the findings of previous reports regarding the cost-efficiency of biosimilar pegfilgrastim products compared with reference standard and pegylated filgrastimCitation20–24.
Because the OBI device delivers a single dose of prophylactic pegfilgrastim, device failure could lead to missed or partial doses of pegfilgrastim, which could compromise CIN/FN prophylaxis. By modeling the cost of FN-related hospitalization resulting from device failure in a panel of 15,000 patients with cancer at risk for CIN/FN, the additional hospitalization costs ranged from approximately $500,000 at 1% failure rate to more than $3 million at 7% failure rate. The number of patients who could be negatively affected by the device failure could exceed 1,000, leading to more than 100 patients with FN-related hospitalizations.
These findings demonstrate that biosimilar pegfilgrastim-jmdb is a clinically relevant, cost-efficient, and safe alternative to reference pegfilgrastim-OBI for CIN/FN prophylaxis. The NCCN guidelines recommend that patients receiving myelosuppressive anticancer therapy with FN risk of more than 20% should receive prophylactic G-CSF within 24 to 72 h of the chemotherapy treatmentCitation2. However, real-world evidence increasingly suggests that G-CSF could be safely administered on the same day of receiving chemotherapy, eliminating the need to return to the clinical facility the next dayCitation11,Citation12. Moreover, due to the COVID-19 pandemic, the NCCN recommends that patients self-administer G-CSF to reduce the frequency of their visits to the clinic and the possibility of contracting COVID-19.
Our economic analyses have several strengths. The study considers various scenarios, including prophylaxis over 1 to 6 cycles of treatment and a range of pegfilgrastim-OBI device failure rates of 1% to 7%, which aligns with real-world evidence. The study is based on up-to-date CMS ASP prices. The methodology of cost-efficiency and budget-neutral expanded access allocation has been validated across a series of peer-reviewed publications, most of which are referenced herein. A limitation of this study is that it utilizes simulation modeling and needs to be validated with real-world data, including actual treatment costs and conversion rates, as well as OBI device-failure rates, consequences of failure (e.g. hospitalization and mortality), and failure-associated costs. Moreover, studies are needed that consider the intangible clinical or patient-related direct and indirect costs associated with receiving assured and uncompromised prophylaxis, as well as studies that consider the cost-to-clinical-benefit relationship to those patients receiving expanded access to prophylaxis or treatment, who under set budgets may not have been provided with prophylaxis or treatment.
Conclusion
This economic simulation in a panel of 15,000 patients with cancer at risk for CIN/FN demonstrates that pegfilgrastim-jmdb is cost-efficient compared with reference pegfilgrastim-OBI, with and without accounting for pegfilgrastim device failure. The cost-savings afforded by conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb could provide additional patients with prophylaxis or anticancer treatment on a budget-neutral basis. Biosimilars are a cost-responsible alternative to reference biologics.
Transparency
Declaration of funding
This study was funded by Viatris, Inc.
Declaration of financial/other interests
Ali McBride has been a speaker and consultant for Pfizer, Coherus, and Mylan.
Karen MacDonald and Ivo Abraham are equity shareholders of Matrix45, LLC, and, by company policy, are prohibited from owning equity in client organizations (except through mutual funds or other independently administered collective investment instruments) or contracting independently with client organizations. Matrix45 provides similar services to those described in this article to other biopharmaceutical companies on a non-exclusive basis.
Adolfo Fuentes-Alburo is an employee of Viatris.
Ivo Abraham is the Deputy Editor-in-Chief of the Journal of Medical Economics and was not involved in the editorial processing or decisions related to this manuscript.
JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
The authors involved in the conception and design or analysis/interpretation and review of the manuscript are Ali McBride, Karen MacDonald, Adolfo Fuentes-Alburo, and Ivo Abraham.
Previous presentations
The study was presented at the 2020 American Society of Hematology Annual Meeting: McBride A, MacDonald K, Abraham I. Conversion to biosimilar pegfilgrastim-jmdb from pegfilgrastim with on-body injector device in diffuse large B-cell lymphoma: Simulation modeling of cost-savings and budget-neutral expanded access to prophylaxis and anti-neoplastic therapy considering device failure rate. Blood. 2020;136(Suppl 1):22.
Acknowledgements
Technical, editorial, and medical writing assistance were provided under the direction of the authors by Yasser Heakal, PhD, and Strategix, an affiliate of The Lynx Group LLC under funding by Viatris, Inc.
References
- Averin A, Silvia A, Lamerato L, et al. Risk of chemotherapy-induced febrile neutropenia in patients with metastatic cancer not receiving granulocyte colony-stimulating factor prophylaxis in US clinical practice. Support Care Cancer. 2021;29(4):2179–2186.
- National Comprehensive Cancer Network [Internet]. NCCN clinical practice guidelines in oncology. Hematopoietic growth factors. Plymouth (PA): NCCN; 2020; [cited 2020 Dec 28]. Available from: www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf
- Lyman GH, Dale DC, Culakova E, et al. The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2013;24(10):2475–2484.
- Lyman GH, Reiner M, Morrow PK, et al. The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy. Ann Oncol. 2015;26(7):1452–1458.
- Lyman GH, Yau L, Nakov R, et al. Overall survival and risk of second malignancies with cancer chemotherapy and G-CSF support. Ann Oncol. 2018;29(9):1903–1910.
- Cerchione C, De Renzo A, Di Perna M, et al. Pegfilgrastim in primary prophylaxis of febrile neutropenia following frontline bendamustine plus rituximab treatment in patients with indolent non-Hodgkin lymphoma: a single center, real-life experience. Support Care Cancer. 2017;25(3):839–845.
- Cerchione C, De Renzo A, Nappi D, et al. Pegfilgrastim in primary prophylaxis of febrile neutropenia in elderly patients with hematological malignancies-bendamustine and G-CSF support. Support Care Cancer. 2019;27(5):1587–1588.
- Kubo K, Miyazaki Y, Murayama T, et al. A randomized, double-blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma. Br J Haematol. 2016;174(4):563–570.
- Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8–32.
- National Comprehensive Cancer Network [Internet]. NCCN clinical practice guidelines in oncology. Hematopoietic growth factors short-term recommendations specific to issues with COVID-19 (SARS-CoV-2). Plymouth (PA): NCCN; 2020; [cited 2020 Dec 28]. Available from: www.nccn.org/covid-19/pdf/HGF_COVID-19.pdf.
- Gascón P, Aapro M, Ludwig H, et al. Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study). Support Care Cancer. 2016;24(2):911–925.
- Ludwig H, Gascón P, Bokemeyer C, et al. Outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (Zarzio®) initiated “same-day” (< 24 h), “per-guidelines” (24–72 h), and “late” (> 72 h): findings from the MONITOR-GCSF study. Support Care Cancer. 2019;27(6):2301–2312.
- US Food and Drug Administration supplemental approval letter of Neulasta® Onpro®; [cited 2021 January 14]. Available from: www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/125031Orig1s170,s179,s181ltr.pdf.
- Mahler LJ, DiBlasi R, Perez A, et al. On-body injector: an administration device for pegfilgrastim. Clin J Oncol Nurs. 2017;21(1):121–122.
- Joshi RS, Egbuna OI, Cairns AS, et al. Performance of the pegfilgrastim on-body injector as studied with placebo buffer in healthy volunteers. Curr Med Res Opin. 2017;33(2):379–384.
- Stuessy P, Sanchez FA, Schober M. Retrospective review of pegfilgrastim on-body injector delivery rates in a large health system [abstract e18273. J Clin Oncol. 2017;35(15_suppl):e18273–e18273.
- Townley C, Porter C, McMullen N. Comparing grade 4 neutropenia associated with pegfilgrastim administered via the Onpro device versus manual injection with a prefilled syringe. J Hematol Oncol Pharm. 2018;8(3):3397.
- US Food and Drug Administration [Internet]. 2018. FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment; [cited 2020 December 6]. Available from: www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-neulasta-help-reduce-risk-infection-during-cancer-treatment.
- Waller CF, Ranganna GM, Pennella EJ, et al. Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia. Ann Hematol. 2019;98(5):1217–1224.
- McBride A, Krendyukov A, Mathieson N, et al. Febrile neutropenia hospitalization due to pegfilgrastim on-body injector failure compared to single-injection pegfilgrastim and daily injections with reference and biosimilar filgrastim: US cost simulation for lung cancer and non-Hodgkin lymphoma. J Med Econ. 2020;23(1):28–36.
- MacDonald K, McBride A, Alrawashdh N, et al. Cost-efficiency and expanded access of prophylaxis for chemotherapy-induced (febrile) neutropenia: economic simulation analysis for the US of conversion from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv. J Med Econ. 2020;23(12):1466–1476.
- McBride A, Balu S, Campbell K, et al. Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz. Future Oncol. 2017;13(25):2285–2295.
- McBride A, Campbell K, Bikkina M, et al. Cost-efficiency analyses for the US of biosimilar filgrastim-sndz, reference filgrastim, pegfilgrastim, and pegfilgrastim with on-body injector in the prophylaxis of chemotherapy-induced (febrile) neutropenia. J Med Econ. 2017;20(10):1083–1093.
- Sun D, Andayani TM, Altyar A, et al. Potential cost-savings from chemotherapy-induced febrile neutropenia with biosimilar filgrastim and expanded access to targeted antineoplastic treatment across the European Union G5 countries: a simulation study. Clin Ther. 2015;37(4):842–857.
- McBride A, Wang W, Campbell K, et al. Economic modeling for the US of the cost-efficiency and associated expanded treatment access of conversion to biosimilar pegfilgrastim-bmez from reference pegfilgrastim. J Med Econ. 2020;23(8):856–863.
- Aapro M, Cornes P, Abraham I. Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia. J Oncol Pharm Pract. 2012;18(2):171–179.
- Chrischilles E, Delgado DJ, Stolshek BS, et al. Impact of age and colony-stimulating factor use on hospital length of stay for febrile neutropenia in CHOP-treated non-Hodgkin’s lymphoma. Cancer Control. 2002;9(3):203–211.
- Centers for Medicare and Medicaid Services [Internet]. 2020 ASP drug pricing files: ASP drug pricing files July 2020. Woodlawn (MD): CMMS; 2020; [cited 2020 June 3]. Available from: www.cms.gov/medicare/medicare-part-b-drug-average-sales-price/2020-asp-drug-pricing-files.
- Centers for Medicare and Medicaid Services [Internet]. CMS-1717-FC Medicare Program: Changes to Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs, Addendum B.-Final OPPS Payment by HCPCS Code for CY. Woodlawn (MD): CMMS; 2020; [cited 2020 June 3]. Available from: www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/Hospital-Outpatient-Regulations-and-Notices-Items/CMS-1717-FC.
- Tai E, Guy GP, Dunbar A, et al. Cost of cancer-related neutropenia or fever hospitalizations, United States, 2012. J Oncol Pract. 2017;13(6):e552–e561.
- Official Data Foundation. Medical Care Inflation Calculator; [cited 2020 June 3]. Available from: www.officialdata.org/Medical-care/price-inflation/2012-to-2020?amount=25676.