With the rapid decline in average sales price of reference pegfilgrastim products due to biosimilar competition, health care institutions and payers may grapple with coverage of Neulasta Onpro.
Am J Manag Care. 2023;29(3):e69-e70. https://doi.org/10.37765/ajmc.2023.89331
Pegfilgrastim (Neulasta) prefilled syringe (PFS), approved by the FDA in 2002, is a long-acting, pegylated, granulocyte colony-stimulating factor used to reduce the incidence of febrile neutropenia (FN).1,2 FDA-approved labeling of pegfilgrastim PFS—both the reference product and its biosimilars—recommends injection between 14 days before and 24 hours after cytotoxic chemotherapy administration.1,3-6 In contrast, Neulasta Onpro, approved in 2014, is an on-body device that injects pegfilgrastim 27 hours after application, offering convenience to patients by avoiding the need for a next-day appointment.1
In April 2021, the National Comprehensive Cancer Network (NCCN) hematopoietic growth factor guidelines were updated, noting that “based on clinical trial data, pegfilgrastim can be administered the day after myelosuppressive chemotherapy (Category 1). There are data for and against same-day dosing, but the FDA-approved dosing schedule is still recommended.”7 In the only double-blind prospective trial addressing this issue, the investigators looked at same-day vs next-day administration in 4 disease groups: breast cancer, non–small cell lung cancer (NSCLC), non-Hodgkin lymphoma (NHL), and ovarian cancer.8 The ovarian cancer arm did not accrue enough patients for evaluation, the NSCLC arm did not have enough FN events for evaluation, and the NHL arm showed no difference in FN. However, the breast cancer arm had a significant difference in FN as those who received same-day administration had 3 times the FN rate.8 There was a noninferior, 1-day greater duration of severe neutropenia in those in the breast cancer and NHL arms who received same-day pegfilgrastim.8 Other retrospective reviews concluded that there was a higher incidence of FN in adult patients with NHL who received same-day pegfilgrastim.9 Conversely, several retrospective studies examining real-world data have found no difference in outcomes between same-day and next-day administration.7,10,11
Insurance companies may cover same-day pegfilgrastim administration despite FDA product labeling, but coverage decisions are regional and plan specific. Select Medicare Administrative Contractors will cover same-day pegfilgrastim or biosimilar PFS, particularly for situations in which patients are believed to be nonadherent to next-day administration.12
Considering reduced costs for pegfilgrastim biosimilars—both financial and time toxicity—health care organizations may struggle with addressing equitable care and reducing expenditures.13 Reference Neulasta PFS and Onpro are assigned the same Healthcare Common Procedure Coding System (HCPCS) code by CMS, J2506, and organizations are reimbursed at parity.14 CMS announced the decision to assign biosimilars separate HCPCS codes in calendar year (CY) 2018, and CMS reimburses biosimilars at the biosimilar average sales price (ASP) plus 8% of the reference product’s ASP.14-16 Although it was initially postulated that the reference product’s ASP would remain unaffected, that has not been observed for pegfilgrastim.14,16 Current FDA-approved biosimilar pegfilgrastim PFS products include Ziextenzo, Udenyca, Fulphila, and Nyvepria. Biosimilar pegfilgrastim entered the US market in November 2019; from January to October 2021, the ASP for J2505 declined by 27.9%, whereas the wholesale acquisition cost (WAC) for Neulasta PFS and Onpro increased by 3% from January 2018 through August 2021.17 Biosimilar pegfilgrastim PFS provides a 34.5% to 38.8% discount off WAC compared with Neulasta PFS and Onpro.17 For pegfilgrastim in the first quarter (Q1) of 2022, the reimbursement ranged from $2012 for Neulasta PFS and Onpro to $2143 to $2917 for pegfilgrastim biosimilars, and the WAC for pegfilgrastim biosimilars ranged from $3925 to $4175 compared with $6418 for Neulasta PFS and Onpro.17 Using Q1 2022 ASP, many institutions presumably experienced a loss of margin on reference Neulasta PFS or Onpro for Medicare beneficiaries, whereas reimbursement for biosimilars appeared to be better.
Per the publicly available Medicare Part B and Part D provider utilization and payment databases, for CY 2020, Medicare Part B spent $899,790,554 (67,120 beneficiaries) on Neulasta PFS and Onpro; $228,090,346 (18,132 beneficiaries) on Udenyca; $74,247,739 (6623 beneficiaries) on Fulphila; and $16,097,120 (1579 beneficiaries) on Ziextenzo.18 For CY 2020, Medicare Part D spent $32,688,655 (1406 beneficiaries) on Neulasta Onpro; $41,020,941 (1613 beneficiaries) on Neulasta PFS; $8,343,087 (542 beneficiaries) on Udenyca; $4,748,957 (318 beneficiaries) on Fulphila; and $543,666 (50 beneficiaries) on Ziextenzo.19 The mean cost to CMS per beneficiary was $23,249 for Neulasta Onpro; $25,431 for Neulasta PFS; and $13,733 for pegfilgrastim biosimilar.18,19 If Part D patients receiving Neulasta PFS were treated with a pegfilgrastim biosimilar in 2020, CMS could have saved $18,868,911. Other publications note that Medicare Part D spending was $2109 lower and estimate patient cost to be $159 lower for pegfilgrastim biosimilars compared with the reference product.20 To quantify this based on 2020 utilization for reference pegfilgrastim, Medicare Part D could have saved $6,367,071 by using biosimilars, and patients could have saved $480,021.
Although Neulasta Onpro is more convenient to patients, is the cost differential compared with biosimilars worth the convenience? It likely is too risky for institutions to move to same-day pegfilgrastim administration without endorsement from NCCN and American Society of Clinical Oncology (ASCO) guidelines, as safety and efficacy data for same-day administration are not robust enough at this time, and deviation from the FDA label and NCCN/ASCO guidelines may put reimbursement at risk. Health care data claims extraction or prospective studies evaluating the safety and efficacy of same-day pegfilgrastim should be pursued and sent to the NCCN and ASCO for guideline consideration.
Time will tell whether payers push pegfilgrastim biosimilar PFS to the pharmacy benefit for patient self-administration and how that affects out-of-pocket spending for patients. Access may be a barrier, particularly for vulnerable populations and individuals with low health literacy or disabilities, if self-administration becomes the sole coverage route.
CMS should consider separating the HCPCS codes for Neulasta PFS and Onpro if it continues to cover reference products. Furthermore, CMS should reconsider its decision to assign separate HCPCS codes to biosimilars and assign under the reference product HCPCS code, because reimbursement would naturally gravitate to the least costly biosimilar, as with generics, resulting in a rapid reduction in health care expenditures. Although the financial benefits in reducing overall health care expenditures are clear, balancing patient satisfaction without FDA and national guideline support for same-day administration of pegfilgrastim adds complexity. Considering the financial burden with Neulasta Onpro, failure rates around 6.9% adding to costs, and evidence to support same-day pegfilgrastim PFS, has Neulasta Onpro finally run its course in capturing market share in the United States?21 Is it time we rip off the Onpro on-body injector and pivot solely to pegfilgrastim biosimilar PFS in the spirit of reducing the overall cost of care?
Author Affiliations: Division of Supply Chain Management (CJJ), Division of Hematology/Oncology (CJS, AD), Division of Hematology (RSG), and Department of Pharmacy (SAS), Mayo Clinic, Rochester, MN; now with Malignant Hematology, Oklahoma Cancer Specialist and Research Institute (CJS), Tulsa, OK.
Source of Funding: None.
Author Disclosures: Dr Jensen reports receiving fees for participating in an Amgen panel on biosimilars in the US landscape at the AMCP Nexus Conference in October 2022 and for a Becker’s Hospital Review webinar in December 2022. Dr Soefje reports consulting for Pi Health and Magnolia Innovations and receiving grants from Janssen and AstraZeneca, honoraria from Pharmacy Times® and CEC Concepts, and lecture fees from ICU Medical. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (CJJ, RSG, SAS); acquisition of data (CJJ, CJS); analysis and interpretation of data (CJJ, AD, RSG); drafting of the manuscript (CJJ, CJS, RSG, AD, SAS); critical revision of the manuscript for important intellectual content (CJJ, CJS, RSG, AD, SAS).
Address Correspondence to: Chelsee J. Jensen, PharmD, BCPS, Division of Supply Chain Management, Mayo Clinic, 200 1st St SW, Rochester, MN 55905. Email: Jensen.firstname.lastname@example.org.
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