https://orcid.org/0000-0001-6386-7582
Abstract
Aims
This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient.
Materials and methods
Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment.
Results
Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio).
Conclusion
This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.
Introduction
Biologics are large molecules manufactured in genetically modified living cells or organisms and are used to diagnose, treat, or prevent disease.Citation1,Citation2 With patents of many of the biologics expiring, biosimilars – that is, biologics that are highly similar to a licensed reference product – have become available and provide an opportunity to reduce pharmaceutical spending and increase access to treatment while offering comparable efficacy and safety.Citation3,Citation4 Biosimilar approvals are based on equivalence studies relative to a reference biologic product in terms of physicochemical properties and clinical evidence.Citation5 In 2005 the European Union implemented a legal framework and regulatory approval pathway for biosimilars, and the first biosimilar, human growth hormone, was approved in 2006, followed by epoetin alfa in 2007 and filgrastim in 2008.Citation3,Citation6,Citation7 In 2012, the United States Food and Drug Administration issued guidance on biosimilar approval requirements, with the first biosimilar, filgrastim-sndz, approved in March 2015.Citation8 Although initially the uptake of biosimilars was slow, they are now commonly used in Europe and increasingly in the US. Other countries, such as the Kingdom of Saudi Arabia (KSA), have more limited experience with biosimilars. Biosimilar guidelines were developed in 2010, while the first filgrastim biosimilar (Zarzio) was approved in 2014.Citation3,Citation9
In oncology, biosimilar agents have been used increasingly as a cost-efficient alternative to reference products. This is especially the case in the supportive care setting, where, for instance, granulocyte colony-stimulating factors (G-CSF) are used to reduce the frequency of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN), which are severe adverse effects of myelosuppressive chemotherapy.Citation10 CIN and particularly FN may lead to significant morbidity and mortality and cause disturbances in chemotherapy regimens (e.g. chemotherapy disruptions, delays, termination; dose reductions).Citation11 Short-acting filgrastim (daily injections until the absolute neutrophil count reaches 10,000/mm3 for a maximum of 14 injections) and long-acting pegfilgrastim (1 injection) have reduced the incidence, severity, and duration of FN.Citation11,Citation12 Prophylaxis with G-CSF is now the standard-of-care for patients receiving myelosuppressive chemotherapy, especially those with risk factors. Per label, G-CSF prophylaxis should be administered no sooner than 24 h after the end (“next-day”) of chemotherapy administration, though real-world evidence suggests that “same-day” administration on the day of chemotherapy administration may be safe for many regimens.Citation13
There are geographic variations in the use of reference and biosimilar G-CSFs. For instance, in the US, single-dose pegfilgrastim is the prevailing regimen, especially now that the next-day administration issue has been bridged by Neulastim OnPro, an on-body injector device that is applied following the end of the chemotherapy session and delivers pegfilgrastim about 27 h after application. In Europe, daily filgrastim retains a significant market share, in part also because real-world evidence has shown that fewer injections, perhaps as few as five, are not associated with an increase in severe CIN or FN and do not increase the likelihood of disturbances to the chemotherapy regimen.Citation10,Citation14,Citation15 There is also anecdotal evidence, at least pre-COVID-19, of daily injections being preferred because of the difference in costs.
A series of cost-efficiency studies in EuropeCitation12,Citation16–18 and the USCitation19–23 demonstrated the most efficient cost structures contributing to the value equation of biological drug treatments, and in particular how cost-efficient savings from biosimilar conversion can be re-allocated to provide more patients with expanded access to drug treatments – and on a budget-neutral basis.Citation18,Citation20,Citation22,Citation24 However, no such data are available for Saudi Arabia, even though there has been a major effort to switch from reference biologics to biosimilars with savings up to 30% expected for cancer care.Citation25,Citation26 In addition, in KSA there is also a shift away from single-injection, long-acting pegfilgrastim to short durations of standard daily filgrastim. The standard of care for primary prophylaxis in oncology centers follows from the guidelines developed by the American Society of Clinical Oncology and the National Comprehensive Cancer Network.
Two filgrastim biosimilars (Nivestim, Zarzio) referencing filgrastim (Neupogen)Footnote1 are available in the KSA through the National Unified Procurement Company (NUPCO) tender. Pegfilgrastim is also available through NUPCO as single-injection Neulastim or on-body injector Neulastim Onpro, as are four biosimilar products referencing the former (Neucyte, Fulphila, Ziextenzo, Nyvepria)Footnote2. In contrast to the US and though available through NUPCO, neither reference pegfilgrastim (Neulastim nor Neulastim OnPro) nor its four biosimilars (Neucyte, Fulphila, Ziextenzo, Nyvepria) have a significant market share in KSA, and standard daily-injection filgrastim prevails (H. Alabdalkarim, personal communication, August 2022). Of note, one large institution, the Ministry of National Guard-Health Affairs, removed pegfilgrastim from the formulary. However, no information is available on the formulary status at other institutions.
In the study reported here, we examined how the efficiencies gained from biosimilar conversion can be applied on a budget-neutral basis to provide (a) more patients undergoing myelotoxic chemotherapy and at risk of CIN/FIN with G-CSF prophylaxis and (b) more women with HER2+ breast cancer with anti-HER2+ directed adjuvant therapy with ado-trastuzumab emtansine after surgery. Breast cancer is the leading cancer in women in Saudi Arabia, with an incidence of 14.2% and a 5-year prevalence of 13,653 patients, of which around 15–20% are HER2+ and require anti-HER2+ therapy.Citation27–30 There is a significant economic burden associated with treating breast cancer. In a retrospective analysis of the economic burden of various stages of breast cancer in KSA, the average cost per patient ranged from $14,249 (stage I) to $81,489 (stage IV).Citation31 Patients with locoregional disease, who constitute 81% of breast cancer patients in KSA,Citation32 are candidates for neo-adjuvant and adjuvant therapy. Around 50% of patients with locoregional disease treated with neoadjuvant therapy may have residual disease.Citation33 HER2+ early-stage breast cancer patients with residual disease should receive ado-trastuzumab emtansine in the adjuvant setting as per international guidelines. Ado-trastuzumab emtansine was approved by the US Food and Drug Administration (FDA) in 2013 for HER2+ metastatic breast cancer in patients who previously received trastuzumab and a taxane, separately or in combination, and received prior therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy.Citation34 In 2019, ado-trastuzumab emtansine gained approval for use in patients with HER2+ early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment based on the results of the Phase III KATHERINE trial.Citation33 Patients with residual disease who received ado-trastuzumab emtansine in the adjuvant setting had a significantly improved probability of invasive disease-free survival.
Building upon the prior cost-efficiency and expanded access simulations in Europe and the US, we report here on the first such study in KSA. Specifically, the aim of this study was to replicate and extend the study by McBride et al.Citation24 with cost-efficiency and expanded access analyses specific to KSA. The objectives of this study were: (1) to simulate the cost-efficiency of converting patients from reference filgrastim (Neupogen) to a biosimilar filgrastim (Nivestim, Zarzio); (2) to simulate the cost-efficiency of converting patients from reference pegfilgrastim (Neulastim/Onpro) to a biosimilar filgrastim (Nivestim, Zarzio) in KSA; to evaluate how reallocating these savings could expand access on a budget-neutral basis (3) to supportive care and provide additional patients with supportive cancer care with biosimilar filgrastim or (4) to breast cancer treatment with ado-trastuzumab emtansine for HER2+ early stage breast cancer in the adjuvant setting along with supportive care with biosimilar filgrastim; and (5) to estimate the number of patients needed to convert (NNC) to a biosimilar filgrastim to provide therapeutic and supportive treatment to one patient.
Methods
Model design
We specified a cost-efficiency and expanded access model to estimate the direct medication acquisition costs and potential savings associated with converting a hypothetical panel of cancer patients requiring (febrile) neutropenia prophylaxis with G-CSF from reference filgrastim or pegfilgrastim to the filgrastim biosimilars Nivestim and Zarzio, and how this affords budget-neutral access to supportive or therapeutic cancer care. It is anticipated that, in KSA, around 400 patients with HER2+ early-stage breast cancer patients with residual disease are potential candidates for ado-trastuzumab emtansine in the adjuvant setting. Therefore, a panel of 4,000 patients with HER2+ early-stage breast cancer patients who are candidates for ado-trastuzumab emtansine in the adjuvant setting was chosen for this model.
The cost of treatment with 300 mcg of reference G-CSF and two biosimilar GCSF products was used in base case and scenario analyses. In the base case analyses, a fixed number of days (5, 6, 7, 11, and 14 days) of filgrastim support were used. Scenario analyses with several real-world durations of support (4.3, 5.4, 6.1, and 6.5 days) complemented the base case analyses. Combining the base case analyses and scenario analyses, a total of 16 prophylaxis durations (eight for Nivestim and eight for Zarzio) were examined.
Cost-efficiency and expanded access
All prices were obtained from NUPCO as a benchmark and reflect the true healthcare expenditures in the public sector in regards to medication costs.Citation35 Calculations were in US dollars. The NUPCO pack price was converted into US dollars using the fixed international exchange rate of 3.75 Saudi Arabian Riyals to 1 USD$.Citation36 Using NUPCO prices shown in , we calculated the potential cost saving impact by assuming substitution of reference G-CSF with its biosimilars at the national level. The revenue and potential saving generated from this switching exercise were used to expand access on a budget-neutral basis to prophylaxis with biosimilar filgrastim or ado-trastuzumab emtansine, as specified above. Additionally, we analyzed how the potential savings lead to expanded access to further supportive care with biosimilar G-CSF. The basis for these analyses is the assumption that cost-savings from the use of biosimilars are re-allocated on a budget-neutral basis to provide access to either therapeutic or supportive cancer care to more patients. Therapeutic care was defined as ado-trastuzumab emtansine 260 mg every 3 weeks for 14 doses. Supportive care was defined as six cycles of prophylaxis with biosimilar G-CSF using five injections per cycle.
Table 1. Treatment costs.
Number-needed-to-convert
The number-needed-to-convert (NNC) metric is a cost-efficiency measure proposed by Sun et al..Citation16 It estimates the number of patients receiving prophylaxis with reference filgrastim/pegfilgrastim who need to be converted to a biosimilar G-CSF to treat one additional patient either with one supportive care treatment with a biosimilar G-CSF or one therapeutic treatment of ado-trastuzumab emtansine. The NNCs were calculated by dividing the cost of treatment with biosimilar filgrastim or ado-trastuzumab emtansine for a panel of 4,000 patients by the potential cost savings generated through a biosimilar switch.
Assumptions
This study is in line with assumptions governing prior economic analyses conducted with biosimilar filgrastim.Citation12,Citation20–23 Equivalence trials have found similar efficacy and safety outcomes for reference filgrastim and biosimilar filgrastim.Citation37–41 Further, as pegfilgrastim was shown to be non-inferior to standard filgrastim, pegfilgrastim can be considered non-inferior to biosimilar filgrastim.Citation19 The hypothetical panel of patients received a myelotoxic chemotherapy regimen with an overall FN risk of a least 20%. Analyses were from the KSA payer perspective in 2022 with the cost inputs and outputs expressed in US dollars. Medication costs were from NUPCO CIF prices, which are used for the public sector.
Results
Cost-efficiency analyses of biosimilar conversion and expanded access to G-CSF prophylaxis
show the potential cost savings and additional patients who can be treated with a biosimilar G-CSF if a panel of 4,000 patients prophylacted with reference filgrastim or pegfilgrastim were switched to a biosimilar filgrastim (Nivestim, Zarzio) in KSA. shows savings per patient ranged between $128.60 (5 days) to $360.08 (14 days) for a switch from reference filgrastim to Nivestim in the base case analysis for one cycle. With a replacement of reference pegfilgrastim with Nivestim, the savings decreased from $488.01 (5 days) to $347.61 (14 days) per patient in one cycle. Prophylacting a single patient with Zarzio for one cycle resulted in greater savings than Nivestim, ranging from $144.20 for 5 days to $403.76 for 14 days, while a switch from reference pegfilgrastim produced savings from $503.61 (5 days) to $391.29 (14 days). The scenario analyses showed similar trends. Note that in the base-case and scenario analyses, the savings from biosimilar conversion increased with treatment duration with reference filgrastim but decreased with reference pegfilgrastim owing to the fact that more daily injections add cost as cycles increase, whereas pegfilgrastim is a single injection.
Table 2. Savings in USD$ from conversion to biosimilar filgrastim in a panel of 4,000 patients for one cycle of G-CSF support.
Table 3. Comparison of savings when shifting from reference filgrastim to Nivestim and Zarzio for six cycles.
Table 4. Comparison of savings when shifting from reference pegfilgrastim to Nivestim and Zarzio for six cycles.
For the entire panel of 4,000 patients receiving treatment in one cycle, savings ranged from $514,400 (5 days) to $1,440,320 (14 days) for conversion from reference filgrastim to Nivestim and ranged from $1,952,040 (5 days) to $1,390,440 (14 days) for conversion from reference pegfilgrastim to Nivestim. The potential savings associated with converting the entire panel of patients from reference filgrastim to Zarzio yielded savings of $576,800 (5 days) to $1,615,040 (14 days). Alternately, conversion from pegfilgrastim to Zarzio yielded potential savings of $2,014,440 with 5 days of prophylaxis, decreasing to $1,565,160 with 14 days of prophylaxis. In the scenario analyses, potential savings ranged from $442,384 (4.3 days) to $668,720 (6.5 days) if the panel of 4,000 patients was shifted from reference filgrastim to Nivestim and from $496,048 (4.3 days) to $749,840 (6.5 days) with a shift from reference filgrastim to Zarzio.
The simulation analyses using the medication costs demonstrated significant savings which, in turn, allow for additional patients to receive supportive care on a budget-neutral basis. The savings are shown by the conversion rates in and . If 100% of the 4,000-patient panel were shifted from filgrastim to Nivestim (), savings would total $3,086,400. Savings declined to $1,543,200 at a 50% conversion rate and to $308,640 at a 10% conversion rate. Shifting from filgrastim to Zarzio () resulted in higher savings, with a potential saving of $3,460,800. At a 50% conversion rate, the saving declined to $1,730,400. At a 10% conversion rate, the potential saving was $346,080.
shows the results for pegfilgrastim with a conversion to Nivestim and Zarzio for six cycles. If 100% of the 4,000-patient panel were shifted from pegfilgrastim to Nivestim, there would be $11,712,240 in savings. Savings declined to $5,856,120 at a 50% conversion rate and to $1,171,224 at a 10% conversion rate. Similar to our findings with filgrastim, there were greater savings with the shift from pegfilgrastim to Zarzio, with a potential savings of $12,086,640. At a 50% conversion rate, the savings declined to $6,043,320. At a 10% conversion rate, the potential savings were $1,208,664.
Expanded access to therapeutic care with ado-trastuzumab emtansine and supportive care with filgrastim
shows the associated expanded access to therapeutic care and supportive care with filgrastim resulting from a 100% conversion from reference filgrastim to biosimilar filgrastim over six cycles. In the base case analysis, an additional 61 patients with HER2+ breast cancer could receive adjuvant treatment with ado-trastuzumab emtansine under the 5-day reference filgrastim to Nivestim scenario, while 8,244 patients could receive access to supportive care. Under the 14-day reference filgrastim to Nivestim scenario, the number of patients with expanded access to ado-trastuzumab emtansine increased to 170 while 23,082 patients would have access to supportive care. In the scenario analyses, the number of patients with expanded access to ado-trastuzumab emtansine ranged from 52 (4.3 days) to 79 (6.5 days). For expanded access to supportive care, it was 7,089 (4.3 days) to 10,717 (6.5 day). With a shift from reference filgrastim to Zarzio with a 5-day scenario, an additional 68 patients had expanded access to ado-trastuzumab emtansine with an increase to 191 additional patients under a 14-day scenario in the base-case analysis. For expanded access to supportive care, there would be 9,244 patients (5 days) up to 25,882 patients (14 days). In the scenario analysis, the number of patients with expanded access to ado-trastuzumab emtansine ranged from 59 (4.3 days) to 89 (6.5 days) and for supportive care from 7,949 (4.3 days) and 12,017 (6.5 days).
Table 5. Expanded access to therapeutic cancer care or supportive care achieved from converting a panel of 4,000 patients from reference filgrastim to biosimilar filgrastim for six cycles.
presents the expanded access to therapeutic and supportive care when the panel of 4,000 patients were shifted from pegfilgrastim to a biosimilar filgrastim over six cycles. The base-case analysis with a conversion from reference pegfilgrastim to Nivestim showed expanded access to ado-trastuzumab for an additional 231 patients under a 5-day filgrastim scenario, decreasing to 164 patients with 14 days of filgrastim prophylaxis. For supportive care there was expanded access for 31,283 (5 days) down to 22,283 (14 days). In the scenario analyses, the number of patients with expanded access to ado-trastuzumab ranged from 236 (4.3 days) to 220 (6.5 days) and from 31,983 (4.3 days) to 29,783 (6.5 days) for supportive care. With a conversion from reference filgrastim to Zarzio, the base-case analysis showed expanded access for ado-trastuzumab emtansine for 238 patients under the 5-day scenario that decreased to 185 patients with 14 days and from 32,283 (5 days) down to 25,083 (14 days) for supportive care. In the scenario analysis, there was expanded access for 242 patients for the 4.3-day scenario, which decreased to 229 patients for the 6.5-day scenario for ado-trastuzumab. In terms of supportive care, expanded access ranged from 32,843 (4.3 days) to 31,083 (6.5 days).
Table 6. Expanded access to therapeutic cancer care or supportive care achieved from converting a panel of 4,000 patients from reference pegfilgrastim to biosimilar filgrastim for six cycles.
Number-needed-to-convert
The NNC estimates are shown in and for various scenarios. Base-case analysis under the reference filgrastim to Nivestim scenarios require an NNC of 395 patients to provide one additional patient with ado-trastuzumab emtansine treatment for 14 cycles under the 5-day scenario, which decreased to 141 patients under the 14-day scenario. In the scenario analyses, the NNC ranged from 459 (4.3 days) to 304 (6.5 days). The base-case analysis under the reference filgrastim to Zarzio scenarios require an NNC of 352 patients to provide one additional patient with ado-trastuzumab emtansine treatment for 5 days of prophylaxis and 126 patients for 14 days of prophylaxis. The scenario analysis shows an NNC of 409 patients (4.3 days) to 271 (6.5 days). For supportive treatment, NNC ranges from 1 to 3 for all scenarios.
Table 7. NNC from reference filgrastim to biosimilar filgrastim to purchase one therapeutic cancer treatment for 14 cycles or supportive care treatment for 6 cycles.
Table 8. NNC from reference pegfilgrastim to biosimilar filgrastim to purchase one therapeutic cancer for 14 cycles or supportive care treatment for six cycles.
shows the NNC from reference pegfilgrastim to biosimilar filgrastim to purchase one therapeutic cancer treatment for 14 cycles. The NNC to convert for the base-case analysis of the shift from pegfilgrastim to Nivestim was 104 for 5 days and increased to 146 for 14 days. In the scenario analysis, the NNC ranged from 102 (4.3 days) to 109 (6.5 days). With the switch to Zarzio from reference filgrastim, the NNC was 101 under the 5-day scenario and increased to 130 under the 14-day scenario. The scenario analysis showed an NNC that ranged from 99 (4.3 days) to 105 (6.5 days). For supportive care treatment, NNC was 1 for all scenarios.
Discussion
Our simulation study for KSA used a hypothetical panel of 4,000 breast cancer patients receiving a myelotoxic chemotherapy regimen requiring G-CSF supportive care and documented the potentially significant savings from converting these patients from standard daily filgrastim (Neupogen) or single-dose pegfilgrastim to biosimilar filgrastim (Nivestim or Zarzio). The savings are a function of the duration of treatment and number of cycles for prophylaxis. The greatest savings were with the biosimilar Zarzio. The trend was an increase in savings with a longer duration of prophylaxis with the shift from filgrastim to a biosimilar filgrastim. For example, substituting filgrastim with Zarzio for the 5-day scenario resulted in a saving of $144.20 and increased to $403.76 for the 14-day scenario; while a shift from pegfilgrastim to a biosimilar filgrastim resulted in lower savings for longer prophylactic durations due to a single fixed dose of pegfilgrastim. Substituting pegfilgrastim with Zarzio resulted in a saving of $503.61 for the 5-day scenario and decreased to $391.29 for the 14-day scenario. The savings gained using a biosimilar growth factor allow more patients to receive therapeutic and supportive cancer treatment. These findings are aligned with those seen in the USCitation19 and Europe.Citation12 Our analyses showed that substitution of reference filgrastim products with biosimilar filgrastim in 4,000 patients may result in expanded access of ado-trastuzumab emtansine use in the adjuvant setting for nearly 40–50% of the HER2+ early-stage breast cancer patients in KSA.
We calculated the potential cost savings impact of substituting reference filgrastim with its biosimilars, assuming one 300 mcg vial of reference filgrastim or its biosimilar is used per patient on a daily basis under all scenarios – 5–14 days. This, in turn, reflects the number of injections used for reference filgrastim and its biosimilars using NUPCO unified prices at the national level. In this regard, it is important to note that, in terms of magnitude, the association between conversion and cost savings is a direct linear function, and this for both conversion to Nivestim and conversion to Zarzio: the cost differential per patient per dose between pegfilgrastim and either of the filgrastim biosimilars is constant and propagated as such through the various days of administration in both the base-case and scenario analyses and, eventually, escalated to a panel of 4,000 patients.
KSA is a leader in the Middle East and North Africa (MENA) region with $1.8 billion in biologics sales, in addition to being the largest biosimilar market in the region.Citation42 There is a strong drive to balance savings with achieving optimal outcomes and making treatment accessible for all. Whereas generic substitution for brand medications generally results in significant savings, this may not always be the case for biosimilar substitution because of indirect costs such as increased testing as a result of the shift or limited price reductions relative to the reference product.Citation26,Citation43 Our analyses showed considerable cost savings and expanded excess with a shift to a biosimilar filgrastim in KSA. By converting to a biosimilar filgrastim, we expect an overall reduction in costs associated with FN and the ability to purchase additional innovative, expensive treatments for more patients on a budget-neutral basis. As other countries in the broader MENA region and local Gulf Cooperation Council region introduce biosimilar policies and various biosimilar products into the market, our findings are encouraging as well as informative to these countries.
Our study has limitations while also identifying areas for future research. It is a simulation study. When available, validation with actual treatment costs and conversion data are needed to confirm our findings. We focused only on the costs of medications and not administration or patient-related costs. While we included both publicly available biosimilars, no data was available on market share for each product. Different conversion rates, cycles, and durations of treatment were modeled to produce robust estimates of savings. Future research should incorporate real-world data of growth factor utilization since under- and over-prophylaxis are possible. Additionally, future economic evaluations may examine the cost-efficiency of switching to biosimilar pegfilgrastim, though in the case of KSA, long-acting pegfilgrastim is not widely used at this time. In addition to a limited market share relative to standard daily filgrastim, reference filgrastim also faces the competition of four pegfilgrastim biosimilars (Neucyte, Fulphila, Ziextenzo, and Nyvepria) available through NUPCO – all with limited market share as well, hence our focus on standard filgrastim.
Conclusion
This first simulation study for KSA demonstrated potentially significant cost-savings through the conversion from reference granulocyte colony-stimulating factor to a biosimilar. These savings generate increased access to cancer treatment and supportive care on a budget-neutral basis. Considering the proven similarity in efficacy and effectiveness, biosimilar uptake should be facilitated across the country and in the MENA region.
Transparency
Author contributions
All authors meet the ICMJE criteria for authorship.
Conceptualization: All authors
Study design: CCY, MAK, IA
Acquisition of data: CCY, IA
Data curation: CCY, IA
Data analysis: CCY, MAK, IA
Data interpretation: CCY, MAK, IA
Manuscript drafting: CCY, MAK, IA
Critical revision of the manuscript for intellectual content: All authors
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Geolocation
Saudi Arabia; Gulf Cooperation Council member countries; Eastern Mediterranean; Middle East.
Acknowledgements
None reported.
Declaration of funding
This study was conducted independently and was not funded by an external authority.
Declaration of financial/other relationships
IA is the Deputy Editor in Chief of the Journal of Medical Economics. IA holds equity in Matrix45, LLC, which provides scientific and consulting services to biopharmaceutical, diagnostics, and medical device companies on a non-exclusivity basis; government and international agencies; and academic or health care institutions. By company policy, owners, employees, and associates are prohibited from holding equity in client and sponsor organizations (except through mutual funds or other independently administered collective investment instruments), contracting independently with client and sponsor organizations, or receiving compensation independently from such organizations. Any compensation related to the provision of services to government and international agencies, academic institutions, and healthcare institutions by equity owners is collected by Matrix45. All other authors report there are no competing interests to declare. With regards to the products mentioned in this article, Matrix45 has provided services to the following manufacturers of licensees of originator and biosimilar granulocyte colony stimulating factors: Amgen, Roche, Sandoz/Novartis, Teva, Hospira/Pfizer, Mylan/Viatris/Biocon, and Coherus Biosciences.
Data availability statement
Requests will be considered by the corresponding author in consultation with other authors as necessary.
Notes
1 Neupogen, filgrastim; Neulastim, pegfilgrastim.
2 KSA does not differentiate between biosimilars as the US does with its 4-letter suffixes, hence we are obliged to use the proprietary drug name for biosimilars in this paper. Nivestim and Zarzio are biosimilars referencing standard filgrastim.
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