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

Abstract

Aims

In this pharmacoeconomic simulation, we: (1) modeled the cost-efficiency of converting patients from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv for prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) from the US payer perspective, (2) simulated how savings enable, on a budget-neutral basis, expanded access to pegfilgrastim-cbqv, and (3) estimated the number-needed-to-convert (NNC) to purchase one additional dose of pegfilgrastim-cbqv.

Methods

In a hypothetical panel of 20,000 patients, we modeled cost-savings utilizing: two reference formulations (pre-filled syringe [PFS] and on-body injector [OBI]), three medication cost inputs (average sales price [ASP], wholesale acquisition cost [WAC], and an age-proportionate blended ASP/WAC rate), administration cost for injection (PFS) and device application (OBI), conversion rates of 10–100%, and 1–6 cycles of prophylaxis. Cost-savings were used to estimate additional doses of pegfilgrastim-cbqv that could be purchased and the NNC to purchase one additional dose.

Results

Using ASP and 10% conversion from reference OBI to pegfilgrastim-cbqv, savings range from $326,744 (1 cycle) to $2.0M (6 cycles) which could provide 93–556 additional doses of pegfilgrastim-cbqv, respectively; the NNC to purchase one additional dose of pegfilgrastim-cbqv ranges from 21.6 (1 cycle) down to 3.6 patients (6 cycles). The WAC model saves $41.1M per cycle and $246.7M over 6 cycles at 100% conversion from reference PFS which could provide 9,709–58,253 additional pegfilgrastim-cbqv doses; the NNC ranges from 2.1 (1 cycle) to 0.3 (6 cycles). Using the blended ASP/WAC rate, converting 50% from reference OBI to pegfilgrastim-cbqv would save $10.2M per cycle and $60.9M over 6 cycles providing 2,638–15,829 additional doses of pegfilgrastim-cbqv; NNCs are 3.8 (1 cycle) and 0.6 patients (6 cycles).

Conclusions

Converting 20,000 patients from reference to pegfilgrastim-cbqv over 6 cycles can generate savings up to $246.7M, enough to purchase up to 58,253 additional doses of pegfilgrastim-cbqv. This simulation provides economic justification for prophylaxis with biosimilar pegfilgrastim-cbqv.

Keywords:

• Pegfilgrastim
• biosimilars
• GCSF
• neutropenia
• febrile neutropenia
• cost-efficiency
• expanded access

JEL CLASSIFICATION CODES:

• I10
• I19

Introduction

Chemotherapy regimens vary in the degree of myelotoxicity and thus the extent to which they suppress the production of neutrophils and cause chemotherapy-induced neutropenia (CIN). Definitions of neutropenia vary, however in oncology the most recent definition of the US National Comprehensive Cancer Network prevails¹: an absolute neutrophil count (ANC) of <500 neutrophils/µL or an ANC of less than 1,000 neutrophils/µL with a predicted decline to ≤500 neutrophils/µL over the next 48 h. If neutropenia is observed in the presence of a single temperature of ≥38.3 °C orally or ≥38.0 °C over 1 h, it is classified as febrile neutropenia (FN). Major dose-limiting toxicity, CIN/FN may require chemotherapy dose reductions, delays, and cancellations and thus impair tumor control and other clinical outcomes, especially in cancers where chemotherapy is curative². Using the 2012 National Inpatient Sample and Kids’ Inpatient Database, a study by the US Centers for Disease Control and Prevention³ estimated that 91,560 adults and 16,859 children were hospitalized for CIN/FN that year at costs of $24,770 and $26,000 per stay, respectively (or, after adjusting for medical inflation, $31,472 and $33,034 in today’s terms).

Nearly three decades of research have demonstrated the efficacy of granulocyte colony-stimulating factors (GCSF) for the prophylaxis of CIN/FN. Primary prophylaxis with GCSF has been shown to significantly decrease the risk of FN in patients receiving myelotoxic regimens including both solid tumors^4–6 and hematological malignancies^7,8 as well as reduce the severity and duration of neutropenia⁹, infection-related hospitalizations¹⁰, the number of chemotherapy disturbances^10,11, and mortality¹².

Chemotherapy regimens are classified according to their FN risk. Regimens with an FN risk ≥20% are classified as “high”. Both the NCCN guidelines¹ and those from the European Organization for Research and Treatment of Cancer (EORTC)¹³ advise to provide primary prophylaxis with GCSF to patients treated with high-toxicity regimens and to assess the need for such agents at the start of each cycle of chemotherapy. For patients scheduled to be treated with regimens with an FN risk between 10 and 20%, these guidelines recommend prophylaxis with GCSF for those patients presenting with such factors as age ≥65 years, advanced cancer, a history of prior FN, poor performance, and/or nutritional status, and liver, renal, and/or cardiovascular disease, among others. No GCSF support is recommended for patients treated with chemotherapy regimens with <10% FN risk.

Biosimilars are non-identical but highly similar versions of approved and marketed biological agents with demonstrated similarity in physicochemical characteristics, efficacy, and safety (including immunogenicity) and no clinically meaningful differences from an existing approved reference product^14–18. Pegfilgrastim-cbqv (Udenycaⁱ) is a biosimilar version of the granulocyte colony-stimulating factor (GCSF) pegfilgrastim (Neulastaⁱⁱ). Like reference pegfilgrastim, pegfilgrastim-cbqv is an injectable solution administered subcutaneously in a single-dose prefilled syringe (PFS). Note that reference pegfilgrastim is also available as an on-body injector (Neulasta Onpro; OBIⁱⁱⁱ) that is applied at the end of chemotherapy administration and is programmed to deliver the medication approximately 27 h later.

Comparative analytics demonstrated that pegfilgrastim-cbqv has a high degree of similarity in structure, pegylation, strength, potency, receptor binding, purity, and stability to its reference, pegfilgrastim^19–21. In the clinical development phase, all pharmacodynamic and pharmacokinetic endpoints were met^19,22. Immunogenicity was assessed in all studies but was the primary focus of one study that found no clinically meaningful treatment-emergent neutralizing antibodies^19,20. Safety outcomes across all studies were similar to those for pegfilgrastim, with bone pain and pain in the extremities being the most common adverse reactions^22,23. Pegfilgrastim-cbqv was approved by the Food and Drug Administration in November 2018 via the Biologics License Application pathway²³.

We report here on a pharmacoeconomic simulation analysis for the US that compares the cost-efficiency of converting patients from CIN/FN prophylaxis with reference pegfilgrastim to prophylaxis with biosimilar pegfilgrastim-cbqv for a hypothetical panel of 20,000 cancer patients treated with myelotoxic chemotherapy regimens. In this analysis, we also simulate how the savings generated from converting patients from reference pegfilgrastim PFS or pegfilgrastim OBI to biosimilar pegfilgrastim-cbqv enable, on a budget-neutral basis, the purchase of additional doses of pegfilgrastim-cbqv for prophylaxis of additional patients above and beyond the 20,000 patients in the panel. We do so across different costing bases (Average Sales Price, Wholesale Acquisition Cost, and an age-proportional blended rate), a number of cycles in which prophylaxis is required, and whether patients are converted from reference pegfilgrastim PFS or pegfilgrastim OBI. For these various scenarios, we also estimate how many of the 20,000 patients need to be converted to GCSF support with pegfilgrastim-cbqv (number-needed-to-convert, NNC) to purchase one additional dose of pegfilgrastim-cbqv.

Methods

Model

The simulation model applied a sequential set of analyses to ascertain the cost-efficiency and expanded access to GCSF prophylaxis with biosimilar pegfilgrastim-cbqv relative to its reference, pegfilgrastim, for a panel of 20,000 covered cancer patients undergoing myelotoxic chemotherapy. In order, we (1) determined the per-patient savings and total savings for a panel of 20,000 patients generated from conversion to pegfilgrastim-cbqv as a function of pricing base, conversion rates, number of cycles of GCSF report, and reference pegfilgrastim formulation; (2) estimated the number of additional patients who could be prophylacted with pegfilgrastim-cbqv on a budget-neutral basis from the various savings scenarios enabled by biosimilar conversion; and (3) calculated the number of patients needed to be converted from prefilled-syringe (PFS) and on-body injector (OBI) formulations of reference pegfilgrastim to purchase 1 additional dose of pegfilgrastim-cbqv.

Using publicly available cost data for medication and administration (see Inputs below for details), we first calculated the cumulative costs of GCSF support with pegfilgrastim-cbqv, pegfilgrastim PFS and pegfilgrastim OBI for one patient for up to six cycles of myelotoxic chemotherapy. From these, we calculated the savings generated by prophylacting one patient with pegfilgrastim-cbqv instead of pegfilgrastim PFS or pegfilgrastim OBI; using biosimilar conversion rates descending from 100 to 10% in decrements of 10%.

These calculations were performed for three costing bases: the Average Sales Price (ASP) as applied to all patients; the Wholesale Acquisition Cost (WAC) as applied to all patients; and an age-proportional blended ASP/WAC (BLEND) price. Specific to the latter, we assumed that patients age 65 and older would be publicly covered by Medicare and, therefore, that the ASP costing base would apply; but that patients under the age of 65 would be privately (i.e. commercially) insured and that the WAC costing base would apply.

Next, the per-patient savings estimates from biosimilar conversion were escalated to a panel of 20,000 patients. We determined the total savings stratified by costing base (ASP, WAC, BLEND), conversion rates (100% down to 10%), number of cycles of GCSF support (1–6), and reference pegfilgrastim formulation (PFS vs. OBI). This yielded a total of 360 savings estimates.

In a third step, we divided each of these estimates by the cost of pegfilgrastim-cbqv to determine the incremental number of additional doses of pegfilgrastim-cbqv that could be purchased on a budget-neutral basis. Importantly, each of the ensuing 360 expanded access results refers to additional doses of pegfilgrastim-cbqv that could be used for prophylaxis above and beyond the prophylaxis already assured for the 20,000 patients in the panel.

Lastly, and looking at the cost-efficiency and expanded access issue from a different angle, we estimated the number of patients needed to be converted (NNC) from pegfilgrastim PFS or pegfilgrastim OBI by costing base and by a number of cycles of GCSF support. More generally, the NNC is defined as the number of patients to be converted from a reference biological to its biosimilar to purchase budget-neutrally one unit of expanded access to a target treatment²⁴. NNC was calculated as follows: Cost of one dose of pegfilgrastim-cbqv/(cost of one dose of pegfilgrastim (PFS or OBI) − cost of one dose of pegfilgrastim-cbqv).

Assumptions

The following assumptions apply.

• Biosimilar pegfilgrastim-cbqv is equivalent in pharmacodynamics, pharmacokinetics, immunogenicity, and safety to pegfilgrastim. This was demonstrated in a study²² in which all pharmacodynamic and pharmacokinetic endpoints were met. Immunogenicity was evaluated in all studies^19,20, and no treatment-emergent neutralizing antibodies and no clinically meaningful differences in emergent anti-drug antibodies were found. Safety outcomes across all studies were similar to those for pegfilgrastim^22,23.

• Following Aapro et al.²⁵ and McBride et al.^26,27, this study is a cost-efficiency analysis that considers only medications and how they are administered. Therefore, it does not include: visit costs, patient co-pays, other patient-related costs (time, travel, meals, lodging, …); indirect, opportunity, or intangible costs; costs associated with the management of chemotherapy-induced (febrile) neutropenia; costs associated with chemotherapy dose reductions, delays, or cancellations; and drug discounts, rebates, or other incentives.

• All patients in the cohort have an overall FN risk of 20% or more. Therefore, patient-, disease- and chemotherapy-related factors are considered equivalent in the model.

• Analyses are from the US payer perspective.

• Costs refer to the sum of medication cost and administration cost.

• Cost input and outputs are expressed in 2020 US dollars.

• One to six cycles of chemotherapy are included.

• Medication costs utilize the most recently available ASP and WAC estimates as publicly available. Administration costs are per the Centers for Medicare and Medicaid Services (CMS) Healthcare Common Procedure Coding System (HCPCS) codes.

• The age-proportional blended ASP/WAC rate assumes that patients age 65 and older are publicly covered by Medicare and, therefore, that the ASP costing base applies; but that patients under the age of 65 are privately (i.e. commercially) insured and that the WAC costing base applies.

• All patients are administered reference or biosimilar pegfilgrastim per label and are assumed to be prophylacted adequately. Failure rates of the pegfilgrastim on-body injector²⁸ are not considered and cost estimates are not adjusted for failure.

Inputs

The ASP for pegfilgrastim PFS and pegfilgrastim OBI is the 1Q2020 reference product ASP, which is the CMS 3Q2020 Medicare Part B Drug payment limit²⁹ minus the 4.3% add-on, to which the applicable administration costs are added (see below). The ASP for pegfilgrastim-cbqv is the 1Q2020 biosimilar ASP, which is the reimbursement limit minus the 4.3% add-on of the reference product, to which the applicable administration cost is added (see below). The WAC inputs are the current 2020 costs as published on the IBM Micromedex RED Book website³⁰, to which applicable administration costs are added. To set the blended ASP/WAC (BLEND) rate, we applied the most recently available (2013–2017) epidemiological estimates from the Surveillance, Epidemiology, and End Results (SEER) Program³¹. Of all newly diagnosed cancer patients, 45.5% were younger than 65 years of age and 54.4% were aged 65 years or older. Thus, we determined the blended rates for pegfilgrastim-cbqv, pegfilgrastim PFS and pegfilgrastim OBI as [(0.4555 × WAC) + (0.5445 × ASP)], to which applicable administration costs are added.

Administration costs were obtained from the CMS Healthcare Common Procedure Coding System (HCPCS) codes³². For pegfilgrastim and pegfilgrastim-cbqv, HCPCS 96372 was applied for administration, while for pegfilgrastim OBI, HCPCS code 96377 (hospital outpatient variant) was used.

Results

Costs of medication and administration

Administration costs were $60.46 for an injection of pegfilgrastim and pegfilgrastim-cbqv compared to $38.11 for applying the pegfilgrastim OBI device (Table 1). Medication costs were the same for pegfilgrastim and pegfilgrastim OBI, ranging from $3,650.33 under the ASP costing base to $6,231.06 under the WAC costing base. The corresponding costs of pegfilgrastim-cbqv ranged from $3,464.61 (ASP) to $4,175.00 (WAC). The age-proportional blended costs were $4,825.86 for pegfilgrastim and pegfilgrastim OBI compared to $3,788.19 for pegfilgrastim-cbqv.

Table 1. Costs of medications and administration.

	Administration^a	ASP^b	ASP + Administration	WAC^c	WAC + Administration	Blended^d	Blended + Administration
Pegfilgrastim-cbqv	$60.46	$3,464.61	$3,525.07	$4,175.00	$4,235.46	$3,788.19	$3,848.65
Pegfilgrastim PFS	$60.46	$3,650.33	$3,710.79	$6,231.06	$6,291.52	$4,825.86	$4,886.32
Pegfilgrastim OBI	$38.11	$3,650.33	$3,688.44	$6,231.06	$6,269.17	$4,825.86	$4,863.97

Abbreviations. OBI, on-body injector; PFS, pre-filled syringe.

^aCMS 2020 Hospital Outpatient Prospective Payment System payment per Healthcare Common Procedure Coding System (HCPCS) code. For pegfilgrastim-cbqv and pegfilgrastim PFS: HCPCS 96372; for pegfilgrastim OBI: HCPCS 96377.

Source: 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 2020. (https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/Hospital-Outpatient-Regulations-and-Notices-Items/CMS-1717-FC).

^bAverage Sales Price. For pegfilgrastim-cbqv: 1Q2020 biosimilar ASP (reimbursement limit minus 4.3 add-on of reference). For pegfilgrastim and pegfilgrastim OBI: 1Q2020 reference ASP (payment limit minus 4.3% add-on).

Source: 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 2020. (https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/Hospital-Outpatient-Regulations-and-Notices-Items/CMS-1717-FC).

^cWholesale Acquisition Cost: 2020 IBM Micromedex RED BOOK.

^dAge-proportional blended ASP and WAC rate, assuming that cancer patients <65 years old (45.55%) have commercial insurance (represented by WAC) and those age 65 and older (54.45%) will have Medicare (represented by ASP). Age proportions are per the most recently reported Surveillance, Epidemiology, and End Results (SEER) Program (2013–2017, all races, both sexes) (https://seer.cancer.gov/statfacts/html/all.html).

Average sales price (ASP): savings, expanded access, and number-needed-to-convert

In this simulation study, due to its slightly lower ASP price but similar administration cost, per-patient savings from prophylaxis with pegfilgrastim-cbqv instead of pegfilgrastim were $186 per cycle for a potential total of $1,114 for a patient requiring prophylaxis for 6 cycles (Table 2). As the administration cost for applying the pegfilgrastim OBI device was $22.35 lower than for a PFS injection, the cost savings from prophylacting a patient with pegfilgrastim-cbqv were $163 per cycle and $980 over 6 cycles of chemotherapy.

Table 2. Per-patient savings from biosimilar conversion to pegfilgrastim-cbqv by number of cycles of GCSF support.

Cycles of GCSF support	1	2	3	4	5	6
Average sales price (ASP) + administration
Cumulative cost of GCSF support across cycles
Pegfilgrastim-cbqv	$3,525	$7,050	$10,575	$14,100	$17,625	$21,150
Pegfilgrastim PFS	$3,711	$7,422	$11,132	$14,843	$18,554	$22,265
Pegfilgrastim OBI	$3,688	$7,377	$11,065	$14,754	$18,442	$22,131
Savings from conversion to pegfilgrastim-cbqv
From Pegfilgrastim PFS	$186	$371	$557	$743	$929	$1,114
From Pegfilgrastim OBI	$163	$327	$490	$653	$817	$980
Wholesale acquisition cost (WAC) + administration
Cumulative cost of GCSF support across cycles
Pegfilgrastim-cbqv	$4,235	$8,471	$12,706	$16,942	$21,177	$25,413
Pegfilgrastim PFS	$6,292	$12,583	$18,875	$25,166	$31,458	$37,749
Pegfilgrastim OBI	$6,269	$12,538	$18,808	$25,077	$31,346	$37,615
Savings from conversion to pegfilgrastim-cbqv
From Pegfilgrastim PFS	$2,056	$4,112	$6,168	$8,224	$10,280	$12,336
From Pegfilgrastim OBI	$2,034	$4,067	$6,101	$8,135	$10,169	$12,202
Age-proportional blended ASP and WAC + administration
Cumulative cost of GCSF support across cycles
Pegfilgrastim-cbqv	$3,849	$7,697	$11,546	$15,395	$19,243	$23,092
Pegfilgrastim PFS	$4,886	$9,773	$14,659	$19,545	$24,432	$29,318
Pegfilgrastim OBI	$4,864	$9,728	$14,592	$19,456	$24,320	$29,184
Savings from conversion to pegfilgrastim-cbqv
From Pegfilgrastim PFS	$1,038	$2,075	$3,113	$4,151	$5,188	$6,226
From Pegfilgrastim OBI	$1,015	$2,031	$3,046	$4,061	$5,077	$6,092

Abbreviations. PFS, pre-filled syringe; OBI, on-body injector.

All estimates are rounded to the nearest dollar.

If all patients in a panel of 20,000 were prophylacted with PFS pegfilgrastim-cbqv instead of PFS pegfilgrastim, total savings were estimated to $3,714,440 per cycle, increasing to $22,286,640 if all patients required 6 cycles of prophylaxis (Table 3). These savings decreased to $371,444 per cycle and $2,228,664 for 6 cycles if only 10% of patients were converted from pegfilgrastim to pegfilgrastim-cbqv. At the 50% conversion mid-point, the corresponding total savings on medication and administration ranged from $1,857,220 (1 cycle) to $11,143,320 (6 cycles).

Table 3. Total savings from biosimilar conversion to pegfilgrastim-cbqv stratified by costing base, conversion rates, and number of cycles of GCSF support in a panel of 20,000 patients.

Cycles of GCSF support		1	2	3	4	5	6
Conversion rate (%)	Patients	Average sales price (ASP) + administration
		Savings from conversion from pegfilgrastim PFS to pegfilgrastim-cbqv
100	20,000	$3,714,440	$7,428,880	$11,143,320	$14,857,760	$18,572,200	$22,286,640
90	18,000	$3,342,996	$6,685,992	$10,028,988	$13,371,984	$16,714,980	$20,057,976
80	16,000	$2,971,552	$5,943,104	$8,914,656	$11,886,208	$14,857,760	$17,829,312
70	14,000	$2,600,108	$5,200,216	$7,800,324	$10,400,432	$13,000,540	$15,600,648
60	12,000	$2,228,664	$4,457,328	$6,685,992	$8,914,656	$11,143,320	$13,371,984
50	10,000	$1,857,220	$3,714,440	$5,571,660	$7,428,880	$9,286,100	$11,143,320
40	8,000	$1,485,776	$2,971,552	$4,457,328	$5,943,104	$7,428,880	$8,914,656
30	6,000	$1,114,332	$2,228,664	$3,342,996	$4,457,328	$5,571,660	$6,685,992
20	4,000	$742,888	$1,485,776	$2,228,664	$2,971,552	$3,714,440	$4,457,328
10	2,000	$371,444	$742,888	$1,114,332	$1,485,776	$1,857,220	$2,228,664
		Savings from conversion from pegfilgrastim OBI to pegfilgrastim-cbqv
100	20,000	$3,267,440	$6,534,880	$9,802,320	$13,069,760	$16,337,200	$19,604,640
90	18,000	$2,940,696	$5,881,392	$8,822,088	$11,762,784	$14,703,480	$17,644,176
80	16,000	$2,613,952	$5,227,904	$7,841,856	$10,455,808	$13,069,760	$15,683,712
70	14,000	$2,287,208	$4,574,416	$6,861,624	$9,148,832	$11,436,040	$13,723,248
60	12,000	$1,960,464	$3,920,928	$5,881,392	$7,841,856	$9,802,320	$11,762,784
50	10,000	$1,633,720	$3,267,440	$4,901,160	$6,534,880	$8,168,600	$9,802,320
40	8,000	$1,306,976	$2,613,952	$3,920,928	$5,227,904	$6,534,880	$7,841,856
30	6,000	$980,232	$1,960,464	$2,940,696	$3,920,928	$4,901,160	$5,881,392
20	4,000	$653,488	$1,306,976	$1,960,464	$2,613,952	$3,267,440	$3,920,928
10	2,000	$326,744	$653,488	$980,232	$1,306,976	$1,633,720	$1,960,464
		Wholesale Acquisition Cost (WAC) + Administration
		Savings from conversion from pegfilgrastim PFS to pegfilgrastim-cbqv
100	20,000	$41,121,200	$82,242,400	$123,363,600	$164,484,800	$205,606,000	$246,727,200
90	18,000	$37,009,080	$74,018,160	$111,027,240	$148,036,320	$185,045,400	$222,054,480
80	16,000	$32,896,960	$65,793,920	$98,690,880	$131,587,840	$164,484,800	$197,381,760
70	14,000	$28,784,840	$57,569,680	$86,354,520	$115,139,360	$143,924,200	$172,709,040
60	12,000	$24,672,720	$49,345,440	$74,018,160	$98,690,880	$123,363,600	$148,036,320
50	10,000	$20,560,600	$41,121,200	$61,681,800	$82,242,400	$102,803,000	$123,363,600
40	8,000	$16,448,480	$32,896,960	$49,345,440	$65,793,920	$82,242,400	$98,690,880
30	6,000	$12,336,360	$24,672,720	$37,009,080	$49,345,440	$61,681,800	$74,018,160
20	4,000	$8,224,240	$16,448,480	$24,672,720	$32,896,960	$41,121,200	$49,345,440
10	2,000	$4,112,120	$8,224,240	$12,336,360	$16,448,480	$20,560,600	$24,672,720
		Savings from conversion from pegfilgrastim OBI to pegfilgrastim-cbqv
100	20,000	$40,674,200	$81,348,400	$122,022,600	$162,696,800	$203,371,000	$244,045,200
90	18,000	$36,606,780	$73,213,560	$109,820,340	$146,427,120	$183,033,900	$219,640,680
80	16,000	$32,539,360	$65,078,720	$97,618,080	$130,157,440	$162,696,800	$195,236,160
70	14,000	$28,471,940	$56,943,880	$85,415,820	$113,887,760	$142,359,700	$170,831,640
60	12,000	$24,404,520	$48,809,040	$73,213,560	$97,618,080	$122,022,600	$146,427,120
50	10,000	$20,337,100	$40,674,200	$61,011,300	$81,348,400	$101,685,500	$122,022,600
40	8,000	$16,269,680	$32,539,360	$48,809,040	$65,078,720	$81,348,400	$97,618,080
30	6,000	$12,202,260	$24,404,520	$36,606,780	$48,809,040	$61,011,300	$73,213,560
20	4,000	$8,134,840	$16,269,680	$24,404,520	$32,539,360	$40,674,200	$48,809,040
10	2,000	$4,067,420	$8,134,840	$12,202,260	$16,269,680	$20,337,100	$24,404,520
		Age-proportional blended ASP and WAC + administration
		Savings from conversion from pegfilgrastim PFS to pegfilgrastim-cbqv
100	20,000	$20,753,219	$41,506,438	$62,259,658	$83,012,877	$103,766,096	$124,519,315
90	18,000	$18,677,897	$37,355,795	$56,033,692	$74,711,589	$93,389,486	$112,067,384
80	16,000	$16,602,575	$33,205,151	$49,807,726	$66,410,301	$83,012,877	$99,615,452
70	14,000	$14,527,253	$29,054,507	$43,581,760	$58,109,014	$72,636,267	$87,163,521
60	12,000	$12,451,932	$24,903,863	$37,355,795	$49,807,726	$62,259,658	$74,711,589
50	10,000	$10,376,610	$20,753,219	$31,129,829	$41,506,438	$51,883,048	$62,259,658
40	8,000	$8,301,288	$16,602,575	$24,903,863	$33,205,151	$41,506,438	$49,807,726
30	6,000	$6,225,966	$12,451,932	$18,677,897	$24,903,863	$31,129,829	$37,355,795
20	4,000	$4,150,644	$8,301,288	$12,451,932	$16,602,575	$20,753,219	$24,903,863
10	2,000	$2,075,322	$4,150,644	$6,225,966	$8,301,288	$10,376,610	$12,451,932
		Savings from conversion from pegfilgrastim OBI to pegfilgrastim-cbqv
100	20,000	$20,306,219	$40,612,438	$60,918,658	$81,224,877	$101,531,096	$121,837,315
90	18,000	$18,275,597	$36,551,195	$54,826,792	$73,102,389	$91,377,986	$109,653,584
80	16,000	$16,244,975	$32,489,951	$48,734,926	$64,979,901	$81,224,877	$97,469,852
70	14,000	$14,214,353	$28,428,707	$42,643,060	$56,857,414	$71,071,767	$85,286,121
60	12,000	$12,183,732	$24,367,463	$36,551,195	$48,734,926	$60,918,658	$73,102,389
50	10,000	$10,153,110	$20,306,219	$30,459,329	$40,612,438	$50,765,548	$60,918,658
40	8,000	$8,122,488	$16,244,975	$24,367,463	$32,489,951	$40,612,438	$48,734,926
30	6,000	$6,091,866	$12,183,732	$18,275,597	$24,367,463	$30,459,329	$36,551,195
20	4,000	$4,061,244	$8,122,488	$12,183,732	$16,244,975	$20,306,219	$24,367,463
10	2,000	$2,030,622	$4,061,244	$6,091,866	$8,122,488	$10,153,110	$12,183,732

Abbreviations. PFS, pre-filled syringe; OBI, on-body injector.

All estimates are rounded to the nearest dollar.

If these same 20,000 patients were converted from the pegfilgrastim on-body injector to injection with pegfilgrastim-cbqv, savings were estimated at $3,267,440 if patients were prophylacted only in cycle 1, rising to $19,604,640 if prophylaxis was given across all 6 cycles. At a 10% conversion rate, total savings declined to $326,744 for 1 cycle and $1,960,464 for 6 cycles of prophylaxis. Converting half of the patients to pegfilgrastim-cbqv was associated with savings of $1,633,720 for 1 cycle of prophylaxis, increasing to $9,802,320 across 6 cycles.

These savings enable budget-neutral expanded access to additional pegfilgrastim-cbqv doses to prophylact additional patients beyond the 20,000 in the panel (Table 4). The savings from converting 20,000 patients from pegfilgrastim to pegfilgrastim-cbqv permit purchasing an additional 1,054 doses of pegfilgrastim-cbqv if all patients are prophylacted for 1 cycle, increasing to 6,322 if all patients are prophylacted for 6 cycles. The corresponding incremental dose counts at 10% conversion are 105 and 632; 527 and 3,161 at 50% conversion.

Table 4. Expanded access to additional pegfilgrastim-cbqv doses that be purchased on a budget neutral basis from conversion to pegfilgrastim-cbqv in a panel of 20,000 patients.

Cycles of GCSF support	Patients	1	2	3	4	5	6
Conversion rate (%)		Average sales price (ASP) + administration
		Additional pegfilgrastim-cbqv doses that can be purchased from conversion from pegfilgrastim PFS
100	20,000	1,054	2,107	3,161	4,215	5,269	6,322
90	18,000	948	1,897	2,845	3,793	4,742	5,690
80	16,000	843	1,686	2,529	3,372	4,215	5,058
70	14,000	738	1,475	2,213	2,950	3,688	4,426
60	12,000	632	1,264	1,897	2,529	3,161	3,793
50	10,000	527	1,054	1,581	2,107	2,634	3,161
40	8,000	421	843	1,264	1,686	2,107	2,529
30	6,000	316	632	948	1,264	1,581	1,897
20	4,000	211	421	632	843	1,054	1,264
10	2,000	105	211	316	421	527	632
		Additional pegfilgrastim-cbqv doses that can be purchased from conversion from pegfilgrastim OBI
100	20,000	927	1,854	2,781	3,708	4,635	5,561
90	18,000	834	1,668	2,503	3,337	4,171	5,005
80	16,000	742	1,483	2,225	2,966	3,708	4,449
70	14,000	649	1,298	1,947	2,595	3,244	3,893
60	12,000	556	1,112	1,668	2,225	2,781	3,337
50	10,000	463	927	1,390	1,854	2,317	2,781
40	8,000	371	742	1,112	1,483	1,854	2,225
30	6,000	278	556	834	1,112	1,390	1,668
20	4,000	185	371	556	742	927	1,112
10	2,000	93	185	278	371	463	556
		Wholesale acquisition cost (WAC) + administration
		Additional pegfilgrastim-cbqv doses that can be purchased from conversion from pegfilgrastim PFS
100	20,000	9,709	19,418	29,126	38,835	48,544	58,253
90	18,000	8,738	17,476	26,214	34,952	43,690	52,427
80	16,000	7,767	15,534	23,301	31,068	38,835	46,602
70	14,000	6,796	13,592	20,388	27,185	33,981	40,777
60	12,000	5,825	11,651	17,476	23,301	29,126	34,952
50	10,000	4,854	9,709	14,563	19,418	24,272	29,126
40	8,000	3,884	7,767	11,651	15,534	19,418	23,301
30	6,000	2,913	5,825	8,738	11,651	14,563	17,476
20	4,000	1,942	3,884	5,825	7,767	9,709	11,651
10	2,000	971	1,942	2,913	3,884	4,854	5,825
		Additional pegfilgrastim-cbqv doses that can be purchased from conversion from pegfilgrastim OBI
100	20,000	9,603	19,207	28,810	38,413	48,016	57,620
90	18,000	8,643	17,286	25,929	34,572	43,215	51,858
80	16,000	7,683	15,365	23,048	30,730	38,413	46,096
70	14,000	6,722	13,445	20,167	26,889	33,611	40,334
60	12,000	5,762	11,524	17,286	23,048	28,810	34,572
50	10,000	4,802	9,603	14,405	19,207	24,008	28,810
40	8,000	3,841	7,683	11,524	15,365	19,207	23,048
30	6,000	2,881	5,762	8,643	11,524	14,405	17,286
20	4,000	1,921	3,841	5,762	7,683	9,603	11,524
10	2,000	960	1,921	2,881	3,841	4,802	5,762
		Age-proportional Blended ASP and WAC + Administration
		Additional pegfilgrastim-cbqv doses that can be purchased from conversion from pegfilgrastim PFS
100	20,000	5,392	10,785	16,177	21,569	26,962	32,354
90	18,000	4,853	9,706	14,559	19,412	24,265	29,119
80	16,000	4,314	8,628	12,942	17,255	21,569	25,883
70	14,000	3,775	7,549	11,324	15,099	18,873	22,648
60	12,000	3,235	6,471	9,706	12,942	16,177	19,412
50	10,000	2,696	5,392	8,088	10,785	13,481	16,177
40	8,000	2,157	4,314	6,471	8,628	10,785	12,942
30	6,000	1,618	3,235	4,853	6,471	8,088	9,706
20	4,000	1,078	2,157	3,235	4,314	5,392	6,471
10	2,000	539	1,078	1,618	2,157	2,696	3,235
		Additional pegfilgrastim-cbqv doses that can be purchased from conversion from pegfilgrastim OBI
100	20,000	5,276	10,552	15,829	21,105	26,381	31,657
90	18,000	4,749	9,497	14,246	18,994	23,743	28,491
80	16,000	4,221	8,442	12,663	16,884	21,105	25,326
70	14,000	3,693	7,387	11,080	14,773	18,467	22,160
60	12,000	3,166	6,331	9,497	12,663	15,829	18,994
50	10,000	2,638	5,276	7,914	10,552	13,190	15,829
40	8,000	2,110	4,221	6,331	8,442	10,552	12,663
30	6,000	1,583	3,166	4,749	6,331	7,914	9,497
20	4,000	1,055	2,110	3,166	4,221	5,276	6,331
10	2,000	528	1,055	1,583	2,110	2,638	3,166

Abbreviations. PFS, pre-filled syringe; OBI, on-body injector.

All estimates are rounded to the nearest integer.

Because of the lower administration costs for pegfilgrastim OBI, 927 additional doses of pegfilgrastim-cbqv can be purchased if 20,000 were converted to pegfilgrastim-cbqv for 1 cycle, rising to 5,561 for 6 cycles. The corresponding yields at 10% conversing range from 93 (1 cycle) to 556 (6 cycles) doses; and from 463 to 2,781 doses at a 50% conversion rate.

The NNC to purchase 1 additional dose of pegfilgrastim-cbqv when converted from pegfilgrastim to pegfilgrastim-cbqv is estimated to be 18.98 if patients are treated for 1 cycle, declining to 3.16 patients if patients are prophylacted for 6 cycles (Table 5). When converting from pegfilgrastim OBI to pegfilgrastim-cbqv, the corresponding NNCs are estimated to be 21.58 (1 cycle of prophylaxis) and 3.60 patients (6 cycles of prophylaxis).

Table 5. Number of patients needed to convert (NNC) to purchase 1 additional dose of pegfilgrastim-cbqv on a budget-neutral basis.

	Number of cycles of GCSF support for a given patient
	1	2	3	4	5	6
	NNC to purchase 1 additional dose of pegfilgrastim-cbqv
Average sales price (ASP) + administration
From pegfilgrastim PFS to pegfilgrastim-cbqv	18.98	9.49	6.33	4.75	3.80	3.16
From pegfilgrastim OBI to pegfilgrastim-cbqv	21.58	10.79	7.19	5.39	4.32	3.60
Wholesale acquisition cost (WAC) + administration
From pegfilgrastim PFS to pegfilgrastim-cbqv	2.06	1.03	0.69	0.51	0.41	0.34
From pegfilgrastim OBI to pegfilgrastim-cbqv	2.08	1.04	0.69	0.52	0.42	0.35
Age-proportional blended ASP and WAC + administration
From pegfilgrastim PFS to pegfilgrastim-cbqv	3.71	1.85	1.24	0.93	0.74	0.62
From pegfilgrastim OBI to pegfilgrastim-cbqv	3.79	1.90	1.26	0.95	0.76	0.63

Abbreviations. PFS, pre-filled syringe; OBI, on-body injector.

Wholesale acquisition cost (WAC): savings, expanded access, and number-needed-to-convert

Simulation analyses using the WAC as costing base revealed potential per-patient savings from prophylaxis with pegfilgrastim-cbqv versus pegfilgrastim of $2,056 per cycle, increasing to $12,336 for a patient being prophylacted for 6 cycles (Table 2). Considering the lower administration cost for the pegfilgrastim OBI, the per-patient cost savings from prophylacting a patient with pegfilgrastim-cbqv are estimated to be $2,034 per cycle and $12,202 over 6 chemotherapy cycles.

Prophylacting all 20,000 patients in the panel with pegfilgrastim-cbqv versus pegfilgrastim generates total savings of $41,121,200 per cycle and $246,727,200 if all patients are prophylacted for 6 cycles (Table 3). These savings decline to $4,112,120 per cycle and $24,672,720 for 6 cycles at a 10% conversion rate. At 50% conversion, the corresponding total savings range from $20,560,600 (1 cycle) to $123,363,600 (6 cycles).

Converting the entire panel of 20,000 from pegfilgrastim OBI to pegfilgrastim-cbqv yields savings of $40,674,200 if prophylacted for one cycle to $244,045,200 if prophylacted for 6 cycles. At a 10% conversion rate, total savings are $4,067,420 for 1 cycle and $24,404,520 for 6 cycles of prophylaxis. Converting 50% of patients to pegfilgrastim-cbqv generates savings of $20,337,100 for 1 cycle and $122,022,600 across 6 cycles.

From these savings, budget-neutral expanded access to additional pegfilgrastim-cbqv doses from converting 20,000 patients from pegfilgrastim to pegfilgrastim-cbqv enables purchasing an additional 9,709 doses of pegfilgrastim-cbqv if patients are prophylacted for 1 cycle, rising to 58,253 if prophylacted for 6 cycles (Table 4). The corresponding incremental pegfilgrastim-cbqv dose counts at 10% conversion are estimated to be 971 and 5,825 doses; and 4,854 and 29,126 doses at 50% conversion.

Due to lower administration costs for pegfilgrastim OBI, expanded access to an additional 9,603 doses of pegfilgrastim-cbqv is possible if all 20,000 patients in the panel received prophylaxis with pegfilgrastim-cbqv for 1 cycle, increasing to 57,620 additional doses for 6 cycles of prophylaxis. The corresponding yields at 10% conversion range from 960 (1 cycle) to 5,762 (6 cycles) additional pegfilgrastim-cbqv doses; and from 4,802 to 28,810 additional doses at 50% conversion.

The NNC to purchase 1 additional dose of pegfilgrastim-cbqv when converting from pegfilgrastim to pegfilgrastim-cbqv is estimated to be 2.06 if patients receive prophylaxis for 1 cycle, declining to 0.34 patients when prophylacted for 6 cycles (Table 5). When converting from pegfilgrastim OBI to pegfilgrastim-cbqv, the corresponding NNCs are 2.08 (1 cycle) and 0.35 patients (6 cycles).

Age-proportional ASP/WAC blended cost (BLEND): savings, expanded access, and number-needed-to-convert

Our simulations using the age-proportional blended ASP/WAC cost showed that converting prophylaxis from pegfilgrastim to pegfilgrastim-cbqv generates potential per-patient cost savings of $1,038 per cycle and $6,226 for 6 cycles (Table 2). The cost savings from prophylacting a patient with pegfilgrastim-cbqv instead of pegfilgrastim OBI are estimated at $1,015 per cycle and $6,092 over 6 cycles.

Converting all 20,000 patients in the panel from pegfilgrastim to pegfilgrastim-cbqv generates total savings of $20,753,219 per cycle and $124,519,315 over 6 cycles (Table 3). Total savings decline to $2,075,322 per cycle and $12,451,932 over 6 cycles at a 10% conversion rate. A 50% conversion to pegfilgrastim-cbqv is associated with potential total savings between $10,376,610 (1 cycle) and $62,259,658 (6 cycles).

Converting all 20,000 patients from pegfilgrastim OBI to pegfilgrastim-cbqv, savings total $20,306,219 if prophylacted for 1 cycle, rising to $121,837,315 over 6 cycles. Converting 10% of the panel results in savings of $2,030,622 for 1 cycle and $12,183,732 for 6 cycles of prophylaxis. Converting 50% of the panel to pegfilgrastim-cbqv saves $10,153,110 for 1 cycle and $60,918,658 for 6 cycles.

In terms of budget-neutral expanded access to additional pegfilgrastim-cbqv doses, prophylacting 20,000 patients with pegfilgrastim-cbqv instead of pegfilgrastim would enable buying an additional 5,392 doses of pegfilgrastim-cbqv if patients are prophylacted in 1 cycle and 32,354 additional doses if they are prophylacted for 6 cycles (Table 4). At 10% conversion, the corresponding incremental dose counts are 539 (1 cycle) and 3,235 (6 cycles). At 50% conversion, between 2,696 (1 cycle) and 16,177 (6 cycles) additional doses of pegfilgrastim-cbqv can be bought.

As the reimbursement rate for administering the pegfilgrastim OBI device is lower, expanded access to 5,276 additional doses of pegfilgrastim-cbqv can be purchased at a 100% conversion rate if the 20,000 patients in the panel received 1 cycle of prophylaxis with pegfilgrastim-cbqv, rising to 31,657 additional doses over 6 cycles. At 10% conversion, the corresponding additional dose counts extend from 528 (1 cycle) to 3,166 (6 cycles); and from 2,638 to 15,829 doses at 50% conversion.

The NNC to purchase 1 additional dose of pegfilgrastim-cbqv when converting from pegfilgrastim to pegfilgrastim-cbqv is 3.71 if patients receive prophylaxis for 1 cycle, declining to 0.62 patients when prophylacted for 6 cycles (Table 5). When converting from pegfilgrastim OBI to pegfilgrastim-cbqv, the corresponding NNCs are 3.79 (1 cycle) and 0.63 patients (6 cycles).

Discussion

Our economic simulation analyses demonstrate that, across scenarios combining three costing bases, ten reference-to-biosimilar conversion rates, and one to six cycles of GCSF support, pegfilgrastim-cbqv consistently generates cost-efficiencies over pegfilgrastim and pegfilgrastim OBI that can be applied to purchase additional doses of pegfilgrastim-cbqv and thus provide expanded access to CIN/FN prophylaxis to patients undergoing myelotoxic chemotherapy on a budget-neutral basis. Across all three costing bases (ASP, WAC, and age-proportional ASP/WAC BLEND) and regardless of the number of cycles requiring GCSF support, the per-patient savings from prophylaxis with pegfilgrastim-cbqv was between $163 (1 cycle of pegfilgrastim OBI prophylaxis at ASP) and $12,336 (6 cycles of pegfilgrastim at WAC). Escalated to a hypothetical panel of 20,000 patients in which patients are converted to biosimilar pegfilgrastim-cbqv, this translates into associated total savings ranging from, respectively, a low of $326,744 (at 10% conversion) to a high of $246,727,200 (at 100% conversion). In turn, these savings enable purchasing, respectively, between 93 and 58,253 additional doses of pegfilgrastim-cbqv to prophylact additional patients on a budget-neutral basis. The findings confirm those of previous (independent and sponsored) simulations of the economics of daily biosimilar filgrastim in Europe^25,33 and the US^26,27 at actual market rates; as well as European simulation analyses for biosimilar epoetin alfa^34,35.

A novel approach over prior simulations of biosimilar GCSF conversion for the US is that we applied the ASP used by CMS for the age 65+ population of Medicare patients, the WAC to reflect pricing and cost dynamics in the commercial health insurance markets, and an age-proportional blended rate based on the distribution of the age of cancer diagnosis as reported by SEER Program. This enhanced the clinical validity of our simulations and offers a tool for provider organizations to assess the likely reimbursement rates for medications and their administration based on their case-mix. Note in this regard that, more generally, the ASPs for reference and biosimilar pegfilgrastim formulations are quite close together and that the Medicare reimbursement of biosimilar pegfilgrastim is pegged to reimbursement for the reference agent. Consequently, the price difference between the ASP of the reference and that of the biosimilar is smaller than that of the WAC, as was evident in our simulation. Nonetheless, Medicare spending for CIN/FN prophylaxis could be reduced in a 20,000-patient panel by $3,650,334 at the lower reimbursement rate for biosimilar pegfilgrastim-cbqv.

Despite its price being the same as pegfilgrastim PFS and differing only in the lower administration costs, including pegfilgrastim OBI adds to the clinical validity of our simulations as well. Although off-label and not advocated here, there has been a trend in recent years to administer the growth factor on the same day as chemotherapy. In its 2015 recommendations for white blood cell growth factors, the American Society of Clinical Oncology advised that “clinicians should not be prohibited from using same-day pegfilgrastim if it provides the only feasible means of CSF administration for certain patients” (p. 3208)³⁶. The 2020 NCCN guidelines for hematopoietic growth factors¹ state “that some institutions have administered pegfilgrastim on the same day as chemotherapy for logistical reasons and to minimize travel burdens on long-distance patients”. The current SARS-CoV-2 pandemic and the associated exposure risk may further discourage patients from returning to the clinic the following day and recently published guidance on the management of vulnerable cancer patients during the SARS-CoV-2 pandemic includes minimizing the number of outpatient visits to mitigate exposure risk³⁷. Yet even before the SARS-CoV-2 pandemic, real-world evidence suggests that same-day administration of short- and long-acting GCSF is increasingly common practice. For instance, the European MONITOR-GCSF study³⁸ (2010–2013) reported that 13.4% of patients received biosimilar filgrastim on the day of chemotherapy compared to 56.4% within the guideline-recommended 24–72 h post-chemotherapy and 30.1% after this time window. A recent study by IBM Watson Health and Amgen found that, in the period from January 2017 to May 2018, 58.4% of reference pegfilgrastim administrations were “early” or same-day as chemotherapy³⁹. While the pegfilgrastim OBI device enables clinicians to administer reference pegfilgrastim per label in the 24–72 h post-chemotherapy time window, failure and malfunction rates between 1.7 and 6.9%^40–43 have been reported. Extrapolated to a panel of 20,000 patients, this implies that between 340 and 1,380 patients, respectively, would not be prophylacted.

The additional doses of pegfilgrastim-cbqv that can be purchased on a budget-neutral basis from the savings from biosimilar conversion of 20,000 patients provide expanded access to many additional patients – from those requiring GCSF prophylaxis in only 1 cycle up to, in our simulation, patients who need to be prophylacted in six cycles. Consider, for instance, the expanded access estimates for the scenario in which 50% of the 20,000 patient panel are prophylacted with pegfilgrastim-cbqv instead of pegfilgrastim OBI using the blended ASP/WAC cost base. If these 10,000 patients need only 1 cycle of prophylaxis, the savings of about $10.1 million enable purchasing and administering an additional 2,638 doses for an additional 2,638 patients with 1 cycle of GCSF support; as well as 1,319 patients for 2 cycles, 879 patients for 3 cycles, 659 patients for 4 cycles, 527 patients for 5 cycles, and 439 patients for 6 cycles. If all 10,000 patients needed 6 cycles of growth factor support, the $60.9 million of savings permit administering an additional 15,829 doses to support patients needing 1 cycle of prophylaxis; as well as 7,914 patients for 2 cycles, 5,276 for 3 cycles, 3,957 for 4 cycles, 3,165 for 5 cycles, and 2,638 patients for 6 cycles. The mere order of magnitude of this expanded access underscores the clinical benefit that can be realized from biosimilar conversion to pegfilgrastim-cbqv.

In fact, the NNC results emphasize the relative feasibility of providing expanded access to CIN/FN prophylaxis. Focusing still on the blended ASP/WAC results from pegfilgrastim OBI, here too the number of cycles in which patients need to be prophylacted is an important volume factor. If patients need only 1 cycle of GCSF support, purchasing one additional dose of pegfilgrastim-cbqv is possible for every 3.79 patients converted to pegfilgrastim-cbqv. However, in patients requiring pegfilgrastim-cbqv support for 6 cycles, the NNC drops to 0.63; that is, each patient converted would enable an additional (1/0.63=) 1.59 patients to receive one cycle of pegfilgrastim-cbqv.

This simulation study lends further support to the evolving principle that biosimilars offer a clinical alternative with demonstrable cost savings to their reference products, especially in the commercial health insurance markets. A study by the RAND Corporation estimates that biosimilars will reduce direct spending on biologic drugs between $24 and $150 billion in the 10-year period from 2017 to 2026 – depending on market dynamics, industry commitments, regulatory decisions, and policy changes⁴⁴. As our simulation shows, a major dynamic is whether payers and policymakers will align on what to do with the savings generated. Another important dynamic is whether clinicians, patients, and patient advocacy organizations will overcome their (largely unfounded but nonetheless still fueled) concerns about the efficacy and safety of biosimilars – a situation reminiscent of the era of generics a few decades ago and the Waxman–Hatch Act of 1984. Finally, our simulation presents the price differential to which the manufacturer of the reference drug could respond in terms of price reductions resulting from biosimilar competition. Such reductions in price should, in turn, lead to prescriber response in terms of price elasticity. Noteworthy is an observed ASP reduction of reference pegfilgrastim since the launch of pegfilgrastim-jmdb in 2018 that continued with the launch of pegfilgrastim-cbqv later that year (more recently approved biosimilars pegfilgrastim-bmez and pegfilgrastim-apgf do not yet have sufficient ASP trend data). This reduction in reference ASP has exerted a downward trend in biosimilar ASP and may signal price erosion across the class. A convergence in the price of all pegfilgrastim products (i.e. a narrowing in price differentials) is a possibility. Yet, the realization of savings for biosimilar GCSF use in the US, through competition-driven changes in price and market share, lags behind other countries including Japan and those in the European Union, which may be attributable to a number of barriers, including the inability of a pharmacist to substitute a biosimilar for a reference biologic; absence of financial incentives for prescribers to use biosimilars; biosimilar launch delays and patent infringement litigation; and lack of transparency related to rebates of branded products⁴⁵.

Our analysis has limitations. It is a simulation and therefore based on assumptions, some of which may require further specification or validation. It is focused on budget impact and did not consider clinical or patient-related indirect costs. It concerns one biosimilar pegfilgrastim. While within an ASP pricing context, the findings may be indicative for other biosimilar pegfilgrastim, on the commercial side there may be significant variation in pricing and contracting. We used the SEER estimates for the age distribution of all incident cancer patients to compute the blended rate of drug costs; an unknown proportion of these patients might not receive GCSF prophylaxis due to tumor type, chemotherapy toxicity, and/or individual patient risk factors. We applied publicly available cost inputs and therefore did not have access to rebates, discounts, and other incentives except to the extent that they are integrated into the quarterly ASP adjustments. We assumed all patients received treatment on schedule and did not consider disruption in chemotherapy due to side effects or treatment failure or switching to another type of long-acting or daily GCSF. Future economic research should recalibrate our estimates based on actual conversion rates from real-world evidence using, in the first place, clinical data from retrospective chart reviews or prospective cohort studies and, secondarily, indirect clinical sources such as claims databases. Future studies should also focus on such determinants as payer and provider adoption of biosimilars; failure rates of the pegfilgrastim OBI device; efficacy and safety of same-day administration; and cost consequences of breakthrough FN episodes despite adequate prophylaxis. The present study should be followed by an assessment of the expanded access to therapeutic cancer care, and novel expensive cancer treatments, in particular, that can be achieved from converting prophylaxis to pegfilgrastim-cbqv.

Conclusion

Using a hypothetical panel of 20,000 patients, three costing bases, ten reference-to-biosimilar conversion rates, and one to six cycles of GCSF prophylaxis, converting patients from pegfilgrastim PFS or pegfilgrastim OBI to pegfilgrastim-cbqv PFS can generate savings enough to purchase up to 58,253 additional doses pegfilgrastim-cbqv. This simulation extends prior economic evaluations on the cost savings that can be realized by providing patients with CIN/FN prophylaxis with biosimilar growth factors rather than the reference product and the expanded access to prophylaxis that can be provided to cancer patients on a budget-neutral basis. With pegfilgrastim-cbqv being pharmacotherapeutically similar to the reference product, our simulation provides economic justification for CIN/FN prophylaxis with pegfilgrastim-cbqv in at-risk cancer patients and across insurance models. Future research utilizing real-world data is required to confirm the exact cost-savings that can be achieved in the U.S health care system.

Transparency

Declaration of funding

This Investigator-Initiated Study was sponsored by Coherus BioSciences, Inc., Redwood City, CA, USA.

Declaration of financial/other interests

• AM serves on a Speakers Bureau for Coherus BioSciences, Inc., the study sponsor, and Merck.

• NA has no conflicts to declare.

• KM and IA are owners of Matrix45, which was funded by Coherus BioSciences, Inc. to conduct this Investigator Initiated Study. Matrix45 has received consultancy fees from Sandoz, Mylan, Novartis, Janssen, Rockwell Medical, Terumo, Celgene and MorphoSys. By company policy, owners and employees are prohibited from owning equity in sponsor organizations (except through mutual funds or other independently administered collective investment instruments) or contracting independently with client organizations. Matrix45 provides similar services to other biopharmaceutical companies on a non-exclusivity basis.

• IA serves on a Speakers Bureau for Coherus BioSciences, Inc., the study sponsor.

• IA Deputy Editor-in-Chief of the Journal of Medical Economics. He was not involved in any editorial decisions regarding this manuscript.

• JME peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.

Author contributions

All authors met ICMJE and COPE criteria and contributed substantively to the study as follows:

• Study concept: KM, AM, IA

• Study design: KM, AM, IA

• Model development and simulations: KM, IA

• Review and interpretation of results: KM, AM, NA, IA

• Development of manuscript: KM, IA, NA

• Review of the manuscript for intellectual content: KM, AM, NA, IA

Acknowledgements

None reported.

Notes

i Udenyca is a registered trademark of Coherus Biosciences, Redwood City, CA, USA.

ii Neulasta is a registered trademark of Amgen, Thousand Oaks, CA, USA.

III Neulasta Onpro is a registered trademark of Amgen, Thousand Oaks, CA, USA.