FormalPara Key Points

In the biologic market, the presence of at least two competitors contributes to consistent downward drug re-pricing.

In this nation-level case study of an etanercept (ETN) off-patent market, we demonstrated that tender competition slowly promoted downward trends in drug pricing, which were rapidly reversed after monopoly resurgence.

After renewed market monopoly, financial incentivization strategies fell short of their intended objectives.

Escalating drug prices lead to greater treatment expenditure by the healthcare payer, who may choose to recover higher costs by restricting treatment access.

1 Introduction

Over the past decades, significant progress has been achieved in rheumatology, leading to notable improvements in quality of life for individuals with rheumatic and musculoskeletal diseases (RMDs) [1]. Therapeutic advancements have been substantial during this period, starting with early milestones such as the introduction of glucocorticoid therapy, followed by the widespread adoption of methotrexate and other disease-modifying agents [2]. The subsequent emergence of biologic disease-modifying antirheumatic drugs and, more recently, small-molecule signaling inhibitors has further expanded treatment options. Notably, there has been a shift towards placing the patient at the forefront of management strategies, which has also shaped the research agenda, marking a revolution in the approach to RMDs [3]. Access to biologic drugs varies geographically, with markedly lower access observed in low- and middle-income countries (LAMICs) [4, 5]. Historically, this disparity stemmed from the high annual cost of biologic therapy, which has declined over time, in part due to biosimilar market introduction. The most notable cost reduction has been observed in countries with high market penetration of biosimilars, where the substitution of reference drugs with biosimilars was mandatory and enforced through tender procedures [6]. This phenomenon has been observed regardless of specific tendering models for biologics in each country [7,8,9]. In wealthy nations, with high biologic availability prior to the advent of biosimilars, the decline in annual therapy costs further increased the proportion of patients with RMDs receiving modern therapies [6]. However, in LAMICs, where access to biological drugs remained limited (often due to regulatory barriers), cost reductions did not always translate into broader access. Persistent regulatory barriers are known to restrict the full “biosimilar potential” in cost reductions and improved therapy access [10].

The concept of "affordable biologics" is based on the premise that biosimilars are less expensive than reference drugs (including other innovative therapies), while prescribed for the same clinical indications, with comparable effectiveness. This enables greater accessibility for a wider range of patients at an earlier stage of disease, thereby improving health outcomes in RMD populations. However, cost differences are dependent on a reactive and competitive market, rather than the biosimilar label alone [11]. While costs of biosimilar introduction into clinical practice are much lower than those of reference drugs, we cannot determine their final price without competition and detailed analysis of a given market. New biosimilars face direct competition from reference drugs and other biosimilar agents with the same active substance, though in situations with a limited number of registered biosimilars, the reference drug can also serve as an effective competitor. Over time, the resultant reductions in treatment cost and maintenance of low prices over the long term are expected. Conceptually, under reinvestment of savings, this should facilitate broader access to therapy for a greater number of patients [5].

Biological drug market monopoly is most commonly perceived as the presence of a reference drug prior to the availability of biosimilars. Maintenance of exclusivity for the reference agent, despite the potential future presence of biosimilar competitors, leads to sustained prices and could even stimulate price increases in anticipation of exclusivity loss and future competition (e.g., adalimumab in the USA) [12]. However, there have been no reported instances of market monopolization by a single biological drug during the modern era of biologic biosimilars. In Poland, we observed a unique scenario with market re-monopolization by a biosimilar product, which provides insights into future drug pricing and market behavior using a nationwide perspective, due to near complete healthcare coverage by the public payer (National Health Fund, NHF).

2 Materials and Methods

2.1 Study Design and Setting

This study aimed to evaluate ETN price evolution while covering the timeframe of biosimilar market presence, both in the period of market competition between the reference drug (Enbrel, Pfizer, authorization date 28.04.2010) and two biosimilars—Benepali (SB4, Samsung Bioepis, authorization date 14.01.2016) and Erelzi (GP2015, Sandoz GmbH, authorization date 23.06.2017), and in the period of re-monopolization (by Erelzi).

We analyzed the exact tender-derived drug prices offered to hospitals, rather than regional or national estimates, between November 2017 and December 2023. The first biosimilar was available from 1 July 2016 (Benepali), while the second (Erelzi) was reimbursed from 1 November 2017 [13].

This analysis included 473 tenders for ETN purchase in pre-filled syringes or automatic injectors. Until August 2021, three ETN drugs were reimbursed by the public payer. From September 2021 to June 2022, only Enbrel and Erelzi were covered by public healthcare, while the period from July 2022 marks Erelzi market monopoly[13]. Enbrel 50 mg is currently still only available for psoriasis (PsO) patients, representing < 1% of the market. A full description of study design and setting is available in the Online Supplementary Material (OSM) S1.

2.2 Competition-Driven and Re-Monopoly-Driven Prices

We analyzed tender bids throughout market competition (November 2017 to June 2022) and Erelzi re-monopolization. Tender volume and mean and median prices for all tender offers and winning bids were calculated and further stratified by the last 6 months of market competition and re-monopolization periods.

Additionally, monthly data published by the NHF [14] covering average reimbursement costs during the period of market competition and monopoly were extracted and re-calculated in daily defined dose (DDD) from their earliest availability (January, 2018).

2.3 Real-Life and Estimated Treatment Cost in Re-Monopoly Era

Based on tender volume and ETN prices from winning bids, reimbursement costs were calculated throughout the 18 months of re-monopoly. For homogeneity, analysis was restricted to rheumatological indications alone (99% of market share). Comparative costs that assume market competition pricing (average over the last available 6 months) are provided.

2.4 Hospital Financial Incentives Related to Off-Patent Biologics

We also examined the effectiveness of incentivization strategies that are designated to promote the use of the cheapest drug available. In brief, if the winning drug price is below a threshold pre-set by the public payer (periodically published price in a separate order, significantly lower than the list price), the bidding hospital receives more favorable valuation of associated healthcare services. This includes the diagnostic procedures cost with the value of the funding received twice as high, and the cost of outpatient clinic visits with the value of the benefit 40% higher [15].

The threshold for ETN pricing has consistently decreased over time, but was likely to remain achievable under a competitive market. Based on current downward trends in Enbrel and Erelzi prices and offers that meet the aforementioned price criterion (from the latest period of market competition), we assume that if competition continued, the price for all winning offers would not exceed the threshold value specified by the NHF, which would enable favorable healthcare reimbursement for hospitals.

2.5 Data Source

Detailed tender data were sourced from public platforms aggregating information on healthcare procurement and websites of individual hospitals. Additionally, the Public Information Bulletin was reviewed. Further supplementary information was extracted from the NHF [14,15,16]. All drug prices and costs are reported as net price (final cost is net price + 8% VAT), while the DDD for ETN was calculated based on the World Health Organization (WHO) ATC/DDD index [17]. Currency conversion was based on average euro (€) exchange rates in the last 5 years (1 € = 4.4124 PLN).

2.6 Statistical Analysis

This analysis was conducted in R 4.3.2 (R Core Team, 2023, R Foundation for Statistical Computing, Vienna, Austria) with the use of publicly available packages (tidyverse, rstatix and ggpubr). The presented data represent a population-level analysis and should be treated as exact calculations. Continuous variables were summarized using descriptive statistics with mean (SD) and/or median [IQR], as deemed appropriate. In case of low tender counts, the range was provided. Discrete variables are summarized using counts and proportion. Visualization is performed using ggplot, with the linear trend compared based on linear or loess fit. Due to right-skewness of certain variables (DDD, tender volume), log-transformation was applied to the axis; however, the original unit is preserved after scale tuning.

3 Results

3.1 Tenders’ Share

The preliminary analysis covered a total of 473 tenders. Of these, in 11 no offers were submitted, therefore 462 tenders in which the winner was selected were included in the final analysis (Fig. 1). The total volume of the analyzed tenders was 212,214 200 mg (4 × 50 mg) packages, which is equivalent to 6,063,257 ETN DDD. The volume of tenders during the period of market competition was 160,626 packs (4,589,314 DDD), and during the re-monopoly period it was 51,588 packs (1,473,943 DDD).

Fig. 1
figure 1

Offer prices of the reference etanercept (Enbrel) and etanercept biosimilars (Benepali, Erelzi) along with the order volume (packages number) in individual tenders in 2017–2023 in Poland. Price is expressed in euro (€) and shown for etanercept daily defined dose (DDD)

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Among 462 tenders, the total number of lowest priced tender volume was highest for Erelzi (146,272 packs, 4,179,200 DDD), followed by Enbrel (49,652 packs, 1,418,629 DDD) and Benepali (16,290 packs, 465,429 DDD).

The period of market competition was marked by total tender volume of 94,746 (2,707,028 DDD) for Erelzi, 49,590 (1,416,857 DDD) for Enbrel, and 16,290 (465,429 DDD) for Benepali. However, if we consider the timeframe from 1 July 2022, the total tender volume and DDD equivalent was estimated at 51,526 (1,472,171 DDD) for Erelzi and 62 (1,772 DDD) for Enbrel. Excluding from the period of market re-monopolization four tenders (two for Erelzi and two for Enbrel) in the area of dermatology (ongoing competition in this area between Erelzi and Enbrel), the total tender volume for Erelzi was 50,364 (1,438,971 DDD), which constitutes 100% of won tenders in the field of rheumatology.

3.2 Competition-Driven and Re-Monopoly-Driven Prices

For the whole timeframe, the total of ETN winning bids were highest for Erelzi (over 297 tenders won), with a median [IQR] tender volume of 260 packs [79–540], and corresponding median [IQR] and mean (SD) ETN DDD price (€) of 7.315 [6.177–7.774] and 7.505 (2.041), respectively. For Enbrel with over 113 tenders won, the median [IQR] tender volume was 125 [50–345], with a median [IQR] and mean (SD) price of 7.825 [6.286–10.201] and 8.299 (2.352), respectively, and for Benepali, over 52 tenders, a median [IQR] of 105 [26–232] tender volume was considered and a corresponding median [IQR] and mean (SD) price of 8.579 [7.488–11.553] and 9.488 (2.344) was calculated, respectively.

For the market competition timeframe, the total number of tenders won were also highest for Erelzi (over 215), with a median [IQR] tender volume of 200 [75–455], and corresponding median [IQR] and mean (SD) price per ETN DDD of 7.258 [5.545–7.670] and 7.281 (1.862), respectively. For Enbrel, over 111 tenders, the median [IQR] tender volume was 130 [50–365], with a median [IQR] and mean (SD) price of 7.837 [6.306–10.296] DDD and 8.342 (2.364) DDD, respectively. The estimates for Benepali are equivalent to the calculation for the whole timeframe due to participation only throughout the period of market competition (Table 1).

Table 1 Descriptive statistics for drug price and tender volume over the timeframe of market competition compared across all competitors. The re-monopoly timeframe from 1 July 2022 in the rheumatology sector is also shown
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By contrast, the corresponding figures for the timeframe of limited market competition (re-monopoly period for Erelzi in the field of rheumatology from 1 July 2022) was a median [IQR] tender volume of 366 [110–800] for Erelzi (over 82 tenders), with an estimated median [IQR] and mean (SD) price of 7.774 [7.536–7.774] and 8.093 (2.371).

Since the average for the entire competitive period for individual brands includes higher prices from the initial phase, the average and median prices of winning bids (only winning tenders, regardless of which drug won) for the last 6 months of market competition (44 tenders won by Enbrel or Erelzi) and the last 6 months of re-monopoly (28 tenders won by Erelzi) were also calculated and showed a significant difference between the competition (mean 5.695, SD 0.555, CI 0.169) and the re-monopoly periods (mean 9.710, SD 3.410, CI 1.322) (Table 2).

Table 2 Descriptive statistics for etanercept (ETN) winning bids (price and tender volume) over the time frame of the last 6 months of market competition (1 January 2022–31 June 2022) compared to the last 6 months of re-monopoly (1 July 2023–31 December 2023)
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The difference between the extreme low and high price values in both periods is even more relevant. The lowest price of Erelzi during the competition period was 5.299, and for Enbrell 5.148, and the highest price of Erelzi in the last months covered by the analysis was 15.071–15.825 (seven tenders).

The price of Erelzi from the latest tenders is more than three times higher than the lowest prices of Erelzi and Enbrel from the period of market competition.

During the period of re-monopoly in rheumatology, but with ongoing competition in dermatology, the price equivalent for winning ETN bids for Erelzi (two tenders) was 5.513–6.266 for volumes ranging between 500 and 600, and for Enbrel (two tenders), with a volume ranging between 12 and 50 packs, a price of 5.830–6.346.

Throughout the entire analysis, the observed price decreased during competition and increased during re-monopoly, regardless of order volume (Fig. 2). We show a significant negative relationship between tender size and winning ETN bid (the strongest in the middle phase of competition and the weakest in the final phase when final prices were the lowest) during competition, which was not observed throughout renewed monopoly (Fig. 3). The observed effect was also independent of the number of drugs participating in the tender (Fig. 4).

Fig. 2
figure 2

Scatter plot with loess fit illustrating the drug price change over the whole study timeframe, stratified by the tender’s volume quartiles. The assumed cut-off for the period of market competition defined as ≥ 1 July 2022 is marked with a red vertical line

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Fig. 3
figure 3

Scatter plot with linear fit illustrating the relationship between tender volume and drug price on a yearly basis, including the period of market competition defined as ≥ 1 July 2022. Pearson’s R and corresponding p value are provided

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Fig. 4
figure 4

Scatter plot with linear fit illustrating the relationship between tender volume and drug price stratified according to the number of tender competitors, accounting for the period of market competition defined as ≥ 1 July 2022. Pearson’s R and corresponding p value is provided in the upper left-hand corner. Each dot point represents a singular tender

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NHF data, including the average monthly cost of ETN reimbursement, shows a downward trend from January 2018 to November 2022 (from €17.22 to €5.58 per ETN DDD), followed by a significant cost increase, reaching a maximum level in December 2023 (€7.46), i.e. approximately 25% more (Fig. 5). Referring to the average prices at the beginning of the current analysis, the lowest monthly value from November 2022 equals a price drop of almost 68%, while considering the highest cost from December 2023 a drop of approximately 57%. Bearing in mind the average annual DDD cost from the year preceding the biosimilar market entry (2015) [5], the corresponding values are 80% and 73%.

Fig. 5
figure 5

Reimbursement cost of etanercept (ETN) daily defined dose (DDD) according to the National Health Fund (NHF) data from January 2018 to December 2023. Monthly published data are presented yearly as mean (× sign) and boxplot with error bars

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3.3 Real-Life and Estimated Treatment Cost in Re-Monopoly Era

Based on tender volumes and ETN prices from winning bids, real-life public payer treatment cost for the rheumatology sector in the re-monopoly era was calculated as €11,198,799. The potential reimbursement of ETN treatment, assuming a drug price at the average level from the last 6 months of the competition period, would be €7,779,087. The estimated loss of the public payer related to the reimbursement of ETN treatment (due to lack of competition in this period) was €3,419,712 (Fig. 6).

Fig. 6
figure 6

Real monopoly-driven (orange solid line) vs. potential competition-driven (blue solid line) etanercept cost in July 2022–June 2023 in Poland. The real cost was calculated according to real tender’s volume and current drug price in the analyzed period. The potential cost was calculated based on real order volume and the average price of etanercept in the last 6 months of market competition. Data are expressed in euros (€) and presented as a cumulative annual cost

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3.4 Off-Patent Biologics-Related Hospital Financial Incentives

Based on the current valuation of healthcare services by the public payer, the potential gains in annual revenue of hospitals, derived from ETN use, per patient, are equal to €352–470 (otherwise expressed as €528–705 for 18 months of therapy). This range results from partial differences in valuation of services across hospitals.

In 2022, the upper limit value for ETN price, which entitles hospitals to receive financial benefits, was changed, and amounts to ~ EUR 0.76 per milligram of ETN within the re-monopolization period. In line with earlier projections, for presentation purposes, it is assumed that 3,580 patients were treated with ETN during this period in Poland [10].

We observed all winning bids during re-monopoly were above the NHF threshold for additional compensation (i.e., payer incentives). Assuming competition, tender prices would likely decline below the required threshold, with the total potential hospital loss related to ETN treatment ranging between €1,892,717 and €2,523,623.

4 Discussion

This nationwide study provides an extensive analysis of the ETN price evolution in an off-patent market, covering all RMD drug purchases by the public payer. This real-life scenario demonstrates how re-monopolization, even by a biosimilar, rapidly increases healthcare expenditure, which has negative downstream effects on hospital funds and may lead to treatment restriction for patients, while also reversing the cost reduction previously derived through competition due to biosimilar market introduction. In the Polish case, the root cause of market re-monopolization was the regulator's decision to maintain only one biosimilar drug on market. This was achieved by withdrawal of reference drug reimbursement, with an underlying, illusory belief that the biosimilar drug would not become more expensive.

Access to biologics varies across Europe and is based on the funding of healthcare systems [18, 19]. The initially high prices of biologics have led to regulatory restrictions, such as stringent disease activity thresholds or prior, multiple csDMARD failure. In some countries, entry criteria have relaxed following biosimilar introduction [6, 20]. In Poland, despite reductions in therapy costs [5, 10], regulations have only modestly improved [13].

The number of RMD patients treated with ETN in Poland has substantially increased over a 10-year period [10]. However, the growth rate was not incremental throughout the biosimilar era. The decrease in annual cost of ETN therapy was marked, but still smaller when compared to ADA and INF [5]. Within this study, the total volume of ETN corresponds to 12,573 patient-years of treatment during the competitive period and 3942 patient-years during re-monopoly. The lowest average price from winning tenders throughout the competition period ranged between €7.28 and €9.48. During this time, the highest mean price (€9.48 for Benepali) was derived from one biosimilar drug being available only for a limited time. Later on, even under competition of two drugs, lower prices were maintained in tenders. Importantly, the average prices for the competition period do not fully reflect financial benefits, as they include higher prices from the initial period. We also observed that achieving a lower price at a given time under stable competition is sustainable. This is reflected in the average winning offer price from the last 6 months of competition, which can be treated as a measure of cost reductions (€5.69). Interestingly, during this time, the lowest price was offered by the reference manufacturer (€5.15). This illustrates that repricing of the reference drug is possible and allows for effective market competition with biosimilars. Despite rheumatology dominance with the ETN market (> 99%), individual tenders in dermatology remain insightful. For tenders won by both the reference drug and the biosimilar, the price was significantly lower than in the RMD sector (€5.51–6.34). Of interest, in one dermatology tender, even without a bid from the reference manufacturer, mere awareness of competition stimulated a low bid price. In 2021, the market share of reference ETN in Poland was ~30%, while that of the other less costly TNFis (ADA and INF) was near null [5]. In contrast, reference ADA and INF manufacturers were unable to compete on the market, though low prices were still maintained due to ongoing competition between biosimilars. In Scandinavian countries, in successive years, both biosimilar drugs (SB4 or GP2015) and the reference drug ETN (Enbrel) have won centralized tenders, demonstrating the potential of price shaping by the reference drug [6, 21].

In Europe, the ratio of biosimilar to reference drug users varies, often changing over time in favor of biosimilars [22,23,24,25,26,27,28]. This trend is most pronounced in countries where substitution is mandatory, and determined by tenders. For local tenders, more entities can consistently compete for market share at a given time. However, in centralized tenders, in countries where a single-winner policy applied, only one manufacturer's drug is designated for use at any given time. Our results are in line with other studies that demonstrate all forms of competition ensure market stability and contribute to consistent price reduction [29].

In countries where biosimilar or reference drug use is obligatory and fixed in a tender, various approaches for introducing a new agent exist [19, 21, 29, 30]. Regional- and nation-wide strategies include a mandate of the selected agent for all or only for new patients. Strategies of switching also vary, while algorithms often require downward pricing under a given threshold. It should be noted that all such procedures often entail additional healthcare service costs [21, 31]. In Poland, switching drugs is mandatory regardless of disease activity or difference in drug prices. Patients receive the new agent at their next scheduled appointment, which ensures use of the tender-winning drug in every case, even if its most recent price has increased. Reimbursement remains predicated on the winning price not exceeding the upper financing threshold. However, the list price (financing limit) is often significantly higher than prices obtained in local (hospital) tenders during competitive periods [13], making it feasible to markedly increase the drug price for hospitals in the absence of competition.

No prior studies have described cost evolution in the scenario of a biosimilar remaining as the only drug in an off-patent market. We recorded that under ETN biosimilar monopoly, the average price increased up to €8.09 over the whole timeframe, including a higher increment in the last 6 months (up to €9.71). When comparing monopoly and competition periods, this corresponds to an increase of about 40–70%. Most recent ETN prices have tripled compared with the lowest competitive prices (and were near equal to the upper financing limit) and exceeded the winning offers from the initial broad market period (~ November 2017). Taken together, the annual treatment cost (gross) per patient (based on the last 6 months of monopoly average price) was estimated at €3828, thus exceeding the cost of treatment in 2018. Moreover, when comparing with the highest price that emerged in recent tenders (resultant estimate of €6236), the projected costs exceed those from early 2017. Under current regulations, these price projections are likely to be sustained in the absence of competition.

During the competitive period, we observed a significant relationship between tender volume and winning price, which was not recorded during re-monopoly. Once achieved, higher pricing remains constant and irreversible, with a sudden increase over time, regardless of order size. These data support observations from other countries, where it has been shown that the ability to generate savings is mainly derived from competition [18, 19, 29]. There is also a positive relationship between the saving size and the number of tender competitors, but a negative association with time lag since the drug equivalent entered the market [32]. In our analysis, the possibility of competition among three drugs existed for a limited time, though no marked difference in winning prices could be observed when bids were submitted by two or three manufacturers. This was also observed during a period when the decrease in the price of ETN was reactive.

Tenders settled during the monopoly period have a delayed impact on current projections for ETN reimbursement. Data from the public payer covering the monthly drug cost from January 2018 to December 2023 supports the trend observed in tenders. The average reimbursement cost in June 2022 was €5.68 (ETN DDD, net), reaching its lowest value in November 2022 (€5.58). From the following month, the reimbursement cost steadily increased, reaching €7.46 in December 2023, i.e., the level that was last seen in February 2021. Differences in reimbursement costs published by the NHF (compared to biosimilar tender prices) during re-monopoly stem from continued implementation of contracts concluded during the competitive period. This will likely result in attenuation of expected drug price increases in subsequent months, as we have yet to observe an obvious change in pricing over the most recent tenders.

With biologics nearly entirely funded by the public payer in Poland, the increase in drug prices has direct economic consequences. The loss incurred by the NHF during the period of re-monopoly amounts to almost €3.5 million. However, the net effect of the increasing treatment cost may be lower, in part due to reduced expenditures for healthcare services. In order to encourage wider uptake of biosimilars, various countries are implementing different incentive systems [19, 33,34,35,36]. Studies from various European countries, including Poland, show that the share of off-patent drugs is steadily decreasing, at the expense of more modern on-patent therapies [10, 21, 22, 30]. While selecting the cheapest drug from the off-patent group guarantees its market share, there is no priority over other on-patent drugs, often with different modes of action. Even under comparable efficacy and safety, the physician may decide to choose the more expensive therapy. Therefore, for the patients’ benefit, tangible and non-tangible incentives [37, 38] appear essential to realize the true potential of biosimilars, i.e., effectively treating a greater number of patients under a similar budget [39, 40].

In Poland, the financial incentive strategy is based on higher valuation of healthcare services in hospitals that purchase drugs under NHF-set thresholds (not list price). Consequently, an increase in ETN prices that exceeeds the NHF limits also restricts additional sources of hospital income. We estimate that if all tenders during re-monopolization resulted in a price allowing for favorable financing, hospital gains could theoretically amount to €1.89–2.52 million (overall). The resultant loss for hospitals represents relative cost savings for the public payer. Consequently, the NHF partially covers the costs incurred due to higher priced therapy, but may also result in patients’ limited access to hospitals providing biological treatment.

If maintenance of high pricing continues in Poland, RMD costs may markedly escalate with the rising number of incident cases. ETN prices also affect increases cumulatively in hospital finances, which in case of fixed-funding limits, are likely to restrict the number of services rendered (and thus the number of patients treated). In addition, reduction of the ETN market share may destabilize the local market, ultimately leading to ETN shortages. The present setting in RMDs may prove even more restrictive than the early biologic era. We previously reported that despite the less costly TNFis being widely prevalent in clinical practice, their market share in Poland has consistently declined [10], despite the presence of incentivization strategies, the failure of which has also been reported in other European countries [33]. Communication and countermeasure strategies are likely the main solutions for the Polish dilemma. Policy changes should be discussed with all key stakeholders, while financial incentives should be re-designed, in order to achieve the potential advantages attributed to affordable biologics, while keeping in mind the economic laws of market behavior. On both a provider and a patient level, appropriate educational programs should be encouraged (e.g., regarding effectiveness and safety of less costly biologics). In summary, the maintenance of a healthy market should ideally be regulated with ongoing input from the pharmaceutical, financial, and medical sectors, to provide long-term sustainability and competitiveness [41, 42]. Finally, on a local level, transfering reimbursement (from hospital-based) to the outpatient and pharmacy setting appears to be a crucial factor for increasing biologic availability in Poland.

5 Strengths

This is a nationwide report covering biologic drug price behavior in time periods of market competition and subsequent monopolization by a biosimilar. The dataset encompasses all tender proceedings conducted during the analyzed period, and provides an illustrative scenario of market behavior under re-monopolization, which cannot be perceived as "affordable" in the absence of competition. Price and therapy cost data include exact (final) prices for hospitals rather than list prices, providing a more realistic assessment of healthcare system burden. In contrast to private or mixed healthcare funding, the near complete coverage by the public payer (NHF) also provides a more comprehesive overview.

6 Limitations

The theoretical inaccuracy of public data published in tender-related platforms remains the key concern of this report. This appears unlikely, as the obtained price data and therapy costs align with other records sourced from the public payer in individual years. We are not aware of any potential risk-sharing agreements (e.g., "pay back"), which could (modestly) affect current projections. We also cannot rule out new regulations for monopoly drugs that may be relevant in future tenders. Importantly, the budget impact of prices reported in more recent tenders is likely deferred over time, which means that any performed estimate of healthcare burden (first 18 months of re-monopoly) is likely to be conservative.

7 Conclusions

In the off-patent market, maintaining market competition remains crucial for ensuring low biologic/biosimilar prices. The presented ETN case illustrates how reference drug presence can exert a favorable economic effect in tender-related downward repricing, even in the absence of competition from the concurrent presence of at least two biosimilars. Under market re-monopolization, we observed reversal of final bid prices to initial estimates in just 18 months, starkly contrasting with a 54-month period of gradual price decrease. Currently, the monthly average ETN reimbursement costs do not reflect the full impact of cost increases to the public payer resulting from market monopolization. This report is a national case study that may be replicated when a regulatory (government) or manufacturer decision leads to withdrawal of one product from the market, resulting in another manufacturer's re-monopoly. A number of detrimental effects, for the public payer and patient alike, shortly follow. We also demonstrate how a theoretically sound policy of financial incentives fails when policy maker/manufacturer decision-making precipitates a dynamic increase in drug price.