Market Entry Of Biosimilars Research Articles

A Cross-National Comparison of Biosimilars Pricing in Argentina, Australia, Brazil, and Italy.

Biosimilar medicines are defined as biological products highly similar to an already licensed biological product (RP). The market entry of biosimilars is expected to reduce the costs of biological treatments. This study aims to evaluate the range of differences between the prices of biosimilars and the corresponding RP for biologicals approved in four countries. This is a cross-national comparison of pricing of biosimilars in Argentina, Australia, Brazil, and Italy. The study examined online price databases provided by the national authorities of the investigated countries. Biosimilar price difference was calculated by subtracting the unit price of the biosimilar by the unit price of the RP, and then dividing it by the unit price of the RP. The results were presented as percentage. Brazil had the highest median price reduction (-36.3%) in biosimilars price, followed by Italy (- 20.0%) and Argentina (- 18.6%). All the biosimilars in Italy were priced below the RP presenting a minimum reduction of 6.3%, while in Australia, most of the prices of biosimilars were equal to the RP. In Argentina, one infliximab-biosimilar displayed price above the RP (40.7%) while the lower priced brand had a reduction of 14.4%. Brazil had four biosimilars with prices above the respective RP, including isophane insulin (1), insulin glargine (1) and somatropin (2). The study revealed a marked dispersion in the price's differences between biosimilars and RP across the studied countries. Governments should evaluate whether their policies have been successful in improving affordability of biological therapies.

Ancillary Product Patents to Extend Biologic Patent Life

This study examines all patents associated with biologic litigation to understand how manufacturers use ancillary product patents to delay biosimilar market entry.

HPR52 TNF-Alfa Inhibitor Therapies: Evaluating the Impact of Biosimilars Competition in Italy, Portugal and Spain

The market entry of biosimilars has represented a cost-reduction opportunity for healthcare systems across Europe. To seize this opportunity in the long term, systems’ rely on ensuring a sustainable competitive environment for all the market players. However, European experiences show that the level of competition generated by biosimilars varies by country, care setting and molecule. Biosimilars contribution to attaining price reductions and increased treatments’ access varies consequently. We aim to capture market dynamics for tumor necrosis factor (TNF)-alpha inhibitors in Southern Europe. The rationale behind this study is the need to gain an in- depth understanding on the impact of the competition generated by the availability of biosimilars in diverse market environments.

The Price and Market Share Evolution of the Original Biologics and Their Biosimilars in Finland.

BackgroundBiological drugs are generally expensive and produce a continuously growing share of drug costs. Yet they are essential in the treatment of many chronic diseases. Biosimilars, clinically equivalent to biological originator products, are expected to restrain drug costs in the biological market.ObjectiveThis study aimed to examine the impact of the biosimilar market entry on the prices of the reference products in outpatient care in Finland, investigate the impact of biosimilar market entries on price competition among biological medicinal products, and examine how the prices and market shares of outpatient biosimilars have developed in Finland during 2009–2020.MethodsThis retrospective register study applied data from IQVIA covering national community pharmacy wholesale data between 1 January, 2009, and 31 August, 2020, for somatropin, epoetin, filgrastim, follitropin, insulin glargine, insulin lispro, etanercept, pegfilgrastim, adalimumab, teriparatide, and enoxaparin biosimilars and their reference products, in addition to two relevant insulin products. We determined the monthly wholesale amounts in defined daily doses and wholesale weighted average prices (excluding value-added tax) per defined daily dose for each product. We analyzed the evolution of the price and market shares. We performed a linear segmented regression analysis to examine the impact of the market entry of biosimilars on the prices of reference products.ResultsThe prices of the reference products mainly decreased after the biosimilar entered the market. If the reference product price was not reduced, it was no longer reimbursable after evaluation under the Health Insurance Act, leading to marginal market shares. The changes in the prices of biosimilars were not as remarkable as the changes in the prices of reference products after the biosimilar market entry. For most active substances, biosimilar prices were stable or decreased. The utilization of biosimilars varied widely between different active substances at the end of the observation period.ConclusionsChanges in pricing policy and the public reimbursement scheme related to the market entry of biosimilars were the main reasons for the decrease in the prices of reference products. Therefore, biosimilars did not generate genuine price competition between biological products. In many of the drug groups examined, the market shares of biosimilars have growth potential in the future.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-022-00540-y.

Biological patent thickets and delayed access to biosimilars, an American problem.

Our study seeks to determine whether patent thickets covering biologic drugs are responsible for delayed biosimilar market entry. We compare patent assertions against the same biosimilar drugs across three countries. On average nine to twelve times more patents were asserted against biosimilars in the United States than in Canada and the United Kingdom. Biosimilars also enter the Canadian and UK markets more quickly than they do in the United States following regulatory approval. Later market entry is not a problem when the brand name drug company is asserting high quality patents (i.e. patents covering significant advances). Consequently, we drilled down into the U.S. patent portfolio of one major biologic, Abbvie's Humira drug, and found that it was made up of roughly 80% non-patentably distinct (duplicative) patents linked together by terminal disclaimers, which is permitted under United States Patent and Trademark Office (USPTO) rules. In contrast, there were far less non-duplicative European patents that covered Humira. Patent thickets can allow brand name drug companies to delay biosimilar entry by relying on the high cost of challenging many duplicative patents instead of the quality of their underlying patents. Accordingly, we suggest several policy interventions that may thin these biologic patent thickets.

Association of Generic Competition With Price Decreases in Physician-Administered Drugs and Estimated Price Decreases for Biosimilar Competition

Price decreases of biologic and biosimilar products in Medicare Part B have been minimal, even with biosimilar competition. Medicare reimburses clinicians for biologics and biosimilars differently than for brand-name and generic drugs, which has generated greater price reductions. To characterize the nature of price competition among brand-name and generic drugs under Medicare Part B and to estimate the cost savings to the program of subjecting biologic and biosimilar therapies to a similar price competition. This cohort study analyzed all brand-name drugs and their approved generic versions as well as biologics and biosimilars that were reimbursed under Medicare Part B from quarter 1 of 2005 to quarter 2 of 2021. Two separate data sets were created: brand-name and generic drugs as well as biologics and biosimilars data sets. Brand-name products with generic versions that were introduced before 2005 were excluded, and so were vaccines. Number of generic and biosimilar competitors over time. Price change as a percentage of the brand-name drug or biologic price in the quarter before generic or biosimilar competition. Price change was modeled using a linear, fixed-effects time series regression, with the number of generic or biosimilar competitors as the main covariate. Time was expressed as the number of quarters since the first generic or biosimilar competitor entered the market. Savings were estimated by projecting the regression model of brand-name and generic drug competition to observed biologic and biosimilar competition and by applying the estimated price reduction to actual Medicare spending for those products from 2015 to 2019. Of the 988 Healthcare Common Procedure Coding System codes identified, 50 (5.0%) met the inclusion criteria for the brand-name and generic drug data set and 28 (2.8%) met the criteria for the biologic and biosimilar data set. The first generic competitor was associated with reduced drug prices by 17.0%, the second competitor with a 39.5% decrease, the third competitor with a 52.5% decrease, and the fourth and more competitors with a 70.2% decrease (price decline was measured from brand-name drug price before the first generic competitor rather than from price established with fewer competitors). If biologics and biosimilars were subject to the same Medicare reimbursement framework as brand-name and generic drugs, Medicare spending on these products was estimated to have been 26.6% lower ($1.6 billion) from 2015 to 2019. This study found minimal uptake of biosimilars and limited price reductions for biologics and biosimilars under the current Medicare Part B reimbursement policy. Adopting the bundled biosimilar reimbursement structure for biologic and biosimilar therapies may be associated with substantial savings and encourage greater biosimilar market entry.

Cost to Medicare of Delayed Adalimumab Biosimilar Availability.

Launched in 2002, originator adalimumab (Humira) is the top revenue-generating drug in the United States. Between 2016 and 2019, the US Food and Drug Administration approved 5 adalimumab biosimilars, yet none have been marketed owing to patent dispute settlements. We sought to calculate the cost of this delayed entry to Medicare over this period by estimating the difference between reported spending on originator adalimumab and estimated spending on originator and biosimilar adalimumab products assuming timely biosimilar market entry. Estimates of potential biosimilar spending were calculated based on the following evidence-based projections: (i) market capture of 15% for the first biosimilar and 5.5% for successive biosimilars in their first year on the market, and 5% annually thereafter; (ii) price reductions of 3.5% per year and 2.4% per additional biosimilar entry for originator adalimumab; and (iii) price discounts of 25% at launch, 3.4% per year, and 1.7% per additional biosimilar entry for biosimilar adalimumab. Based on these assumptions, had adalimumab biosimilars launched upon approval, estimated non-rebate spending on them would have been $18.3million in 2016, $225.7million in 2017, $436.2million in 2018, and $727.7million in 2019, whereas estimated non-rebate spending on originator adalimumab would have been $2.33billion, $2.04billion, $1.78billion, and $1.42billion. Cumulative spending on adalimumab would have thus been $8.98billion instead of an observed $12.11billion. Accounting for estimated rebates, total predicted savings would have been $2.19billion. Reforms for timely biosimilar availability will be critical in ensuring optimal savings for Medicare after biosimilar approval.

Off-Patent Biological and Biosimilar Medicines in Belgium: A Market Landscape Analysis.

Background and objective: Best-value biological medicines may generate competition in the off-patent biologicals market, resulting in having more resources available to provide patients with access to necessary medicines while maintaining high-quality care. Belgium is a country known to have low biosimilar market shares, suggesting a malfunctioning market for off-patent biologicals. This study aims to gain an in-depth understanding of the Belgian off-patent biologicals market, by looking at the evolution in volumes and costs of the relevant products in the market. Methods: This study included a combination of quantitative and qualitative research methods. The quantitative part of this study consisted of the analysis of market data obtained by the National Institute for Health and Disability Insurance (NIHDI) for all relevant products in the Belgian off-patent biologicals market (i.e. TNF-inhibitors, insulins, granulocyte colony-stimulating factors, epoetins, rituximab, trastuzumab). In addition, for the qualitative part of this study, semi-structured interviews with Belgian stakeholders were conducted between December 2019 and March 2020. Results: Belgian market data and stakeholder perceptions suggest a suboptimal market environment for off-patent biological and biosimilar medicines. Shifts are observed after loss of exclusivities of originator biologicals toward second-generation products or new therapeutic class products, at a higher cost and often limited added value. Moreover, cost reductions for off-patent biologicals after biosimilar market entry are mainly determined by mandatory price reductions applicable to both originator and biosimilar products, and not by lower prices induced by competition. For products used in the retail setting, significant mandatory price reductions for both originator and reference products with low biosimilar volumes were pointed out as the main reasons for the lack of price competition. For products dispensed in hospitals, the hospital financing system is important. First, it does not always encourage the use of lower cost alternatives. Second, competition mainly takes place at the level of confidential discounts in tenders. Most interviewees acknowledged the lack of a competitive environment, which is not supportive of a sustainable Belgian off-patent biologicals market. Conclusion: Market data and stakeholder perceptions indicate that the sustainability of the Belgian market for off-patent biologicals is challenged. A sustainable market ensures access to biological therapies now and in the future.

Legal Obstacles to Biosimilar Market Entry

Improving the market availability and penetration of biosimilars, “follow-on” versions of biologic products, will require attention to key legal obstacles. Because biosimilars offer the potential for sizeable cost savings to payors and improved access to biologic drugs for patients, obstacles to the timely licensure and market availability of biosimilars are of major public health significance. Issues around intellectual property, potentially anticompetitive contractual arrangements with purchasers and insurers, and laws governing automatic substitution of biosimilars for biologics merit particular attention. This Article examines several key legal obstacles to biosimilar market entry in the United States, including (1) the complexity and imprecise boundaries of the exchange of patent information codified in the BPCIA; (2) patent thickets that protect biologic reference products; (3) unsettled antitrust law surrounding reverse payment patent settlements (i.e., “pay-for-delay” agreements); (4) contractual arrangements such as bundled purchase agreements and formulary exclusivity provisions; and (5) state laws that regulate substitution of biosimilars for biologics at the pharmacy level. Strategies to address these obstacles include reforms to the patent system to curb issuance of ancillary secondary patents intended to delay competition, greater transparency around biologic patents, reconsideration of the need for a regulatory designation of interchangeability, and better detection and enforcement of deliberately anticompetitive practices.

Does Etanercept Biosimilar Prescription in a Rheumatology Center Bend the Medication Cost Curve?

The market entry of biosimilars is expected to bring budgetary relief. Our objective was to determine how the introduction of biosimilars influences medication costs in patients with rheumatoid arthritis (RA) and which patients gain access to biologics due to the availability of biosimilars. Using hospital data of patients with RA between 2014 and 2018, an interrupted time series was performed. The interruption in the time series was placed at June 2016 (i.e., the introduction of the etanercept biosimilar). The changes in trends for rheumatic medication costs before and after the interruption were measured. Secondary analyses focused on explaining these trends. In the first quarter after the interruption, there was a decrease in total costs for biologic users of -€63,020 (95% CI -€96,487 to -€29,553, P = 0.001). The postinterruption trend did not differ from the preinterruption trend (95% CI -€6695 to €6715, P = 0.998) and after 3 quarters, the medication costs were back at the interruption level. After the interruption, the average cost per biologic user decreased by -€370 (95% CI -€602 to -€138, P = 0.005), followed by a quarterly decrease (relative to the preinterruption trend; 95% CI -€86 to -€14, P = 0.010), bending the average cost curve. The percentage of patients being treated with biologics increased in postinterruption by 0.50 percentage points quarterly (95% CI 0.38-0.62, P < 0.001). Also, the average age at the start of the first biologic increased after the interruption (P = 0.057). The average cost per patient treated with biologics decreased after the introduction of biosimilars with a persistent trend. However, the budgetary relief due to market entry of biosimilars vanished quickly due to an increase in patients treated with biologics.

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases.

Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars—biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators—can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.Electronic supplementary materialThe online version of this article (10.1007/s40265-020-01256-5) contains supplementary material, which is available to authorized users.

The Biosimilar Action Plan: An Effective Mechanism for Balancing Biologic Innovation and Competition in the United States?

The strain between balancing pharmaceutical innovation and competition in the United States (U.S.) is centered around the need to ensure that the U.S. continues to encourage medical innovation while simultaneously providing patients with access to affordable and innovative drug treatments. This tension exists whether the drugs at issue are chemically-synthesized or complex large molecule drugs, such as biologics. In 2010, Congress passed the Biologic Price Competition and Innovation Act (BPCIA). The statute created a statutory approval pathway for biological products shown to be biologically similar (biosimilar) to the originator or “brand” biologic, while retaining the same safety, purity, and potency as the brand. Unfortunately, the BPCIA’s provisions failed to accelerate biosimilar product development in the United States and we continue to lag behind Europe in providing patient access to affordable biosimilars. To help stimulate the U.S. biosimilar market, the Food and Drug Administration (FDA) issued the Biosimilar Action Plan (BAP) in July 2018. BAP focuses on four key strategies: 1) streamlining the biosimilar approval and product development process; 2) increasing biosimilar informational resources; 3) maximizing scientific and regulatory clarity; and 4) “getting competitively priced biosimilars into the market by reducing the gaming of FDA requirements and other attempts to unfairly delay competition.” An enhanced informational platform and streamlined approval process should increase the biosimilar approval rate and accelerate biosimilar product development. However, the FDA’s regulatory powers are insufficient to curb the gaming and other anticompetitive behaviors that most negatively impact access, such as: 1) rebating schemes; 2) pay-for-delay agreements; 3) leveraging innovator patent rights to impede biosimilar market entry and 4) other regulatory abuses. Partnerships with key stakeholders, such as Congress, the Federal Trade Commission, States, Non-Governmental Organizations, and Payors are therefore crucial to achieving the BAP’s overarching goal of “promoting competition and affordability [of biosimilars] across the market.” The recently proposed Biologic Patent Transparency Act provides an example of how Congress can work in tandem with the FDA and other stakeholders to foster innovation and build a competitive and sustainable biosimilar marketplace for patients in the U.S.

PBI40 TENDER APPROACHES IN THE OFF-PATENT BIOLOGICAL MEDICINES MARKET: A EUROPEAN COMPARATIVE ANALYSIS

Tendering has become an important strategy to contain spending when purchasing pharmaceuticals. However, tender approaches, such as awarding total market volume to a sole competitor, may threaten the sustainability of the off-patent biological medicines market. This study aims to (i) map the organisation and implementation of tendering across Europe, (ii) investigate tender frameworks and award criteria, (iii) identify best tender practices and (iv) formulate recommendations. First, to gather information on tender implementation and applied frameworks, a quantitative web survey was completed by hospital pharmacists and procurers across Europe. Second, to explore insights and derive learnings, semi-structured interviews were performed with hospital pharmacists, procurers and industry from countries representing different healthcare systems: Norway, Denmark, Italy, UK, France and Belgium. A hundred survey participants representing 26 countries were included for descriptive analysis. Although the implementation and experience with tendering for off-patent biologicals was heterogeneous among participants, similar selection and award criteria were often applied. The majority of participants indicated the use of selection criteria beyond price. Twelve interviews were conducted. Interviewees mentioned the complex trade-off between benefits and risks of national and regional/hospital tendering systems. National systems, representing a larger purchasing capacity, may result in larger discounts, but may also push other competitors out of the market. Regional/hospital systems may be advantageous for long-term competition by providing an opportunity for multiple players, however they may also result in less competitive prices. Some interviewees were apprehensive about the risk of competitors withdrawing from the market due to unexpected high price pressure. Due to variations between regions, national healthcare systems and product classes, it may not be possible to create a ‘one-size-fits-all’ tendering framework. However, overarching best practices towards sustainable tendering for off-patent biologicals were identified, including: (i) multiple winner tenders, (ii) differentiation beyond price and (iii) re-opening of contracts upon biosimilar market entry.

The US Biosimilar Market: Stunted Growth and Possible Reforms.

In 2010, Congress created an abbreviated application pathway for biosimilars, versions of approved biologics made by different manufacturers. However, as of November 1, 2018, the US Food and Drug Administration (FDA) had approved only 13 biosimilars under this pathway, of which just 6 were available for patients to use. We review the history of US regulation of biologics and identify manufacturing, regulatory, and marketing issues that have limited biosimilar market entry and uptake, concluding with recommendations for reform.

Biosimilars: A New Look on Process Innovation and the Impact of Competitive Dynamics

As healthcare costs are rising globally and biologic treatments are a growing segment of the cost, governments have created biosimilar regulatory pathways in attempt to lower the costs of biologics. Since biosimilars are still relatively nascent, the impact of the biosimilars from a practical and academic viewpoint is emerging. This research begins to fill a current gap in the literature, quantitatively evaluating the drivers that firms face regarding entering into the biosimilars market. Further, this research contributes to the practical and academic understanding of process innovation by presenting the biosimilar phenomenon and the competitive dynamics of biosimilar market entry.

Key drivers for market penetration of biosimilars in Europe

ABSTRACTBackground & Objectives: Potential drivers and barriers of biosimilar uptake were mainly analysed through qualitative approaches. The study objective was to conduct a quantitative analysis and identify drivers of biosimilar uptake of all available biosimilars in the European Union (EU).Methods: A three-step process was established to identify key drivers for the uptake of biosimilars in the top 10 EU member states (MS) pharmaceutical markets (Belgium, France, Germany, Greece, Hungary, Italy, Poland, Spain, Sweden, and the UK): (1) literature review to identify incentive policies in place to enhance biosimilars adoption; (2) assessment of biosimilar market dynamics based on database analysis; (3) regression model analysis on price using the following explicative variables: incentive policies; price difference between the biosimilar and the originator product; distribution channel; generic uptake and generic price cut; pharmaceutical expenditure per capita; and market competition.Results: At the study cut-off date, 20 biosimilars were available on the market. Incentive policies applied to biosimilars were found to be heterogeneous across countries, and uptakes of biosimilars were also very heterogeneous between different therapeutic classes and countries. Results from the model demonstrated that incentive policies and the date of first biosimilar market entry were correlated to biosimilar uptake. Pharmaceutical expenditure per capita and the highest generic uptake were inversely correlated with biosimilar uptake. Average generic price discount over originator and the number of biosimilars showed a trend toward statistical significance for correlation with biosimilar uptake, but did not reach the significance threshold. Biosimilar price discount over original biologic price, the number of analogues, and the distribution channel were not correlated with the biosimilar uptake.Conclusions: Understanding drivers of biosimilar uptake becomes a critical issue to inform policy decision-makers. This study showed that incentive policies to enhance uptake remain an important driver of biosimilar penetration, while biosimilar price discounts have no impact. Future research is warranted when the biosimilar market gains maturity.

A high-throughput 2D-analytical technique to obtain single protein parameters from complex cell lysates for in silico process development of ion exchange chromatography

The accelerating growth of the market for biopharmaceutical proteins, the market entry of biosimilars and the growing interest in new, more complex molecules constantly pose new challenges for bioseparation process development. In the presented work we demonstrate the application of a multidimensional, analytical separation approach to obtain the relevant physicochemical parameters of single proteins in a complex mixture for in silico chromatographic process development. A complete cell lysate containing a low titre target protein was first fractionated by multiple linear salt gradient anion exchange chromatography (AEC) with varying gradient length. The collected fractions were subsequently analysed by high-throughput capillary gel electrophoresis (HT-CGE) after being desalted and concentrated. From the obtained data of the 2D-separation the retention-volumes and the concentration of the single proteins were determined. The retention-volumes of the single proteins were used to calculate the related steric-mass action model parameters. In a final evaluation experiment the received parameters were successfully applied to predict the retention behaviour of the single proteins in salt gradient AEC.

Destined for Failure? An Analysis of the Biologics Price Competition and Innovation Act of 2009

In 2010, Congress enacted the Biologics Price Competition and Innovation Act (“BPCIA”) as part of the large health care reform bill. The BPCIA creates a statutory pathway for FDA approval of “biosimilars”––which are generic versions of biologic drugs. Congress expects this new approval pathway for biosimilars to help lower biologics prices, just as generic drugs have significantly lowered pharmaceutical prices. This Note argues that, for three main reasons, the BPCIA will not succeed in lowering drug prices to the same degree that generic pharmaceuticals have. First, biosimilars are more expensive to develop than generic pharmaceutical drugs. Manufacturers will be hesitant to enter the biosimilars market, leading to less competition. Second, biosimilars will struggle more than generics to capture market share from the branded drug. Third, lengthy exclusivity periods awarded to the branded biologic and the first interchangeable biosimilar will substantially delay biosimilar market entry. This Note then concludes with suggestions for improving the BPCIA, both through potential amendments and regulatory process.