Biosimilar Competition Research Articles

The evolution of value with filgrastim in oncology.

The recombinant G-CSF filgrastim was first approved in 1991, and its value has been evolving ever since. Initial health technology assessments suggested low value due to high drug cost and no evidence for significant gain in overall survival. However, more recent meta-analyses of placebo-controlled randomized trial data show falling costs due to biosimilar competition and absolute overall survival gains of 3.2% (95% CI: 2.1-4.2%) from filgrastim support of cytotoxic chemotherapy. The launch of biosimilar alternatives merits a re-evaluation of decisions by health technology assessments and explains the first inclusion of filgrastim in the WHO Essential Drug List for cancer >20years after its original approval in 1991, thus demonstrating the power of biosimilar medicines in transforming healthcare.

PSY83 - IMPACT OF DOSE ESCALATION ON AVERAGE COST AND COST-EFFECTIVENESS OF ANTI-TNF AND USTEKINUMAB IN THE TREATMENT OF MODERATE-TO-SEVERE PLAQUE PSORIASIS IN SWEDEN

Dose escalation for etanercept (ETA), infliximab (INF) and ustekinumab (UST) has been reported in registry studies and is often reported as common clinical practice in moderate-to-severe plaque psoriasis. The aim of this study was to measure the impact of dose escalation on average cost and cost-effectiveness in Sweden. Cost and drug survival were modelled over a 5 year horizon with periods of 4 weeks using dosing according to labelled dose schedule and real-world evidence on drug survival and dose escalation. Dose escalation was estimated from data published from DermBio in Denmark and drug survival was based on a literature review. Costs included were drug costs valued at public price. Infusion costs for INF were excluded. Cost-effectiveness was calculated as cost per PASI100 responder using response rates from a network meta-analysis. Sensitivity analyses were conducted on dose multipliers and price discounts for anti-TNFs, simulating the impact of biosimilars. Dose escalation of ETA, INF and UST increased the expected average costs per 4 week treatment period with 16%-18%. ETA, INF and UST were not cost-effective compared to modern biologics. Sensitivity analyses showed that ETA and UST were cost-ineffective at all levels of dose escalation, while INF was cost-ineffective at dose increases of more than 33% versus anti-IL17’s and anti-IL23’s at current prices. High discounts were required for ETA, INF and UST to be cost-effective (prices of ETA and INF have already been reduced with biosimilar competition in Sweden). Dose escalation increases the cost of ETA, INF and UST. These biological treatments are not cost-effective compared modern biological treatments (anti-IL17’s and anti-IL23’s) at observed levels of dose escalation without higher levels of discounting.

PMU4 - THE SAFETY OF SWITCHING BETWEEN REFERENCE BIOPHARMACEUTICALS AND BIOSIMILARS: A SYSTEMATIC REVIEW

The approval of more complex biosimilars continues to fuel the discussion about switching between reference biopharmaceuticals and biosimilars. To date, there is no consensus among stakeholders about switching, possibly curbing the biosimilar competition potential. This study aims to address the questions about switching from a reference biopharmaceutical to its biosimilar. A systematic literature review of peer-reviewed full-text publications (via Embase, Medline, Cochrane, Web-of-Science) and other available literature up to June 2017 was performed for all products with a biosimilar approved in Europe. Abstracts were updated with full-text publications when available up to December 2017. Currently, an update is performed to extend the search until June 2018. Thus far, 109 unique studies were identified in which switch outcomes were reported. The bulk of the data (69 studies) relate to anti-TNFs (more specifically to CT-P13). Data are emerging for other, more recently approved biosimilars as well. Almost all studies (106 studies) consisted of a single switch from the reference biopharmaceutical to its biosimilar. Data were obtained from studies conducted as part of the biosimilar clinical development, studies in clinical practice and registries. The data do not indicate safety issues or a loss in response due to switching. The majority of the individual studies however was not robust enough to exclude any risk, as this would require studies with a larger sample size and a longer follow-up period. Data on multiple switching are scarce and data on switching between biosimilars are lacking. The updated data will be presented at the ISPOR 2018 congress. Based upon the available switch data, there are no indications that switching is associated with major safety issues or a loss in response. A single switch from a reference biopharmaceutical to a biosimilar could thus be considered under the physician’s supervision. Avoiding frequent switches remains advisable for traceability reasons.

PMS69 - BIOSIMILAR AND ORIGINATOR INFLIXIMAB: INFLUENCE OF LOCAL POLICY MEASURES AND PRACTICES ON MARKET DYNAMICS BETWEEN SWEDISH COUNTIES

This study aims to analyse market dynamics of biosimilar and originator infliximab in Swedish counties, and examines how local policy measures and practices, in addition to national policy, influence market dynamics. First, a structured review of the literature on (biosimilar) policies in Sweden was conducted. Secondly, market data provided by IQVIA on the counties’ originator and biosimilar infliximab uptake (Q2 2012 to Q4 2017) were analysed, including discounts from tender contracts. Thirdly, findings were discussed in interviews with a national health authority, key experts in Skåne, Västra Götaland, and Stockholm, and an industry representative. Wide variations exist in market shares of biosimilar infliximab between counties (18% to 96% in 2017). The initial uptake of biosimilar infliximab was slow and varied widely, with abrupt increments in biosimilar market shares due to expiration of contracts with the originator product. Univariate regression showed a positive non-linear correlation between the cost per defined daily dose (DDD) of the originator and the biosimilar market share, as well as between the price discount of the biosimilar and the biosimilar market share. Different strategies of counties to reduce the cost per DDD of infliximab were identified, i.e., a rapid switch to the biosimilar (Skåne), a late switch to the biosimilar (Stockholm), or no switch to the biosimilar, but a favourable price on the originator product (Västra Götaland). The price difference between originator and biosimilar, presence of KOLs, local guidelines and initiatives in the hospital, and whose budget it affects, were identified as drivers in the decision-making process. This study has shown that counties use different strategies to leverage biosimilar competition. Decreasing the cost per DDD of infliximab does not necessarily imply an uptake of biosimilars, as competition may result in the originator product providing the least expensive treatment option. Different factors were identified that influence decision-making.

The Impact of the Entry of Biosimilars: Evidence from Europe

Biologics represent a substantial and growing share of the U.S. drug market. Traditional “small molecule” generics quickly erode the price and share of the branded product upon entry, however only a few biosimilars have been approved in the US since 2015, thereby largely preserving biologics from competition. We analyze European markets, which have had biosimilar competition since 2006. Using our own survey, we analyze how market features and public policies predict biosimilar entry, price, and penetration, finding significant heterogeneity across countries and products. Effective buyer institutions are associated with increased biosimilar penetration. Our estimates can inform ongoing policy discussions.

Financial costs associated with monopolies on biologic medicines in Australia.

Objectives The aim of the study was to estimate the potential savings to the Pharmaceutical Benefits Scheme (PBS) and the Repatriation Pharmaceutical Benefits Scheme (RPBS) in 2015-16 if biosimilar versions of selected biologic medicines (biologics) had been available and listed on the PBS. Methods The research involved retrospective analysis of Australian Medicare expenditure data and PBS price data from 2015-16 for biologics, for which biosimilar competition may be available in future, listed on the PBS. Results Australian Government expenditure on biologics on the PBS and RPBS was estimated at A$2.29 billion dollars in 2015-16. If biosimilar versions of these medicines had been listed on the PBS in 2015-16, at least A$367million dollars would have been saved in PBS and RPBS subsidies. Modelling based on price decreases following listing of biosimilars on the PBS suggests that annual PBS outlays on biologics could be reduced by as much as 24% through the timely introduction of biosimilars. Conclusions Biologic medicines represent a large proportion of government expenditure on pharmaceuticals. Reducing the length of monopoly protections on these medicines could generate savings of hundreds of millions of dollars per year. What is known about the topic? Biologics take up an increasing share of pharmaceutical expenditure, but no previous published studies have examined Australian Government expenditure on biologics or the potential savings from reducing the duration of monopoly protection. What does this paper add? This paper provides new evidence about Australian Government expenditure on biologics and potential savings for selected medicines that are still subject to monopoly protection and thus are not yet subject to biosimilar competition. In 2015-16 Australian Government expenditure on biologics through the PBS and RPBS was estimated at A$2.29 billion dollars. If biosimilar versions of these medicines had been listed on the PBS at that time, at least A$367million dollars would have been saved. What are the implications for practitioners? Reducing the duration of monopoly protection on biologic medicines could save hundreds of millions of dollars annually that could be redirected to other areas of the healthcare system.

1126P - The evolution of value with filgrastim in oncology

Background: The value of drugs will evolve over time as new evidence for risks and benefits emerge and the price of a drug changes. Methods: A NICE Evidence Search on March 1, 2017 revealed 25 systematic reviews and 55 economic evaluations of filgrastim.1 Results: Initial Health Technology Assessments (HTA) suggested low value due to high drug cost and no evidence for significant gain in Overall Survival (OS). More recent metanalyses of placebo-controlled randomized trial data show absolute OS gains of 3.2% (95% CI:2.1—4.2%) from filgrastim support of cytotoxic chemotherapy2 and falling costs due to biosimilar competition. Conclusions: Physicians and payers need to be aware that HTA decisions need constant re-evaluation, especially following the launch of biosimilar alternatives. This explains the first inclusion of filgrastim in the WHO essential Drug List for cancer more than 20 years after its original approval in 1991,3 and demonstrates the power of biosimilar medicines in transforming healthcare.

Economic aspects of biosimilar competition in Hungary — The treatment of rheumatic disorders

Biologicals are the fastest growing segment of the global pharmaceutical market, reaching 199 billion USD sales per year with 9.8% 10-year compound annual growth rate (CAGR). Being less costly, yet equally efficacious and safe alternatives to originator reference products, biosimilars drive competition, promise budget savings and the opportunity for better patient-access. This paper examines the key factors and players of biosimilar competition in rheumatology in Hungary. Due to the scarcity of data, the total yearly expenditure on biologicals could only be estimated from different data sources. In 2015 the estimated expenditure on biologicals was around 100 billion HUF. In rheumatology indications the expenditure on biologicals was 10 (8.9-11.2) billion HUF, and the average annual net treatment cost was 1.2 (1.06-1.34) million HUF / per patient / year. The magnitude of societal benefits in terms of budget savings and health gains may result from the joint effort of policy makers, funders, physicians and patients. In rheumatology indications, biosimilar utilization could be increased by a policy supporting physician-driven interchange of the reference product to biosimilars. Also, creating a physician incentive system for broader use should be considered in order to realize the full economic advantages of biosimilars and contribute to sustainable healthcare financing in Hungary.

Of patents and patent disputes: The TNFα patent files. Part 1: Humira.

This article discusses the patent strategy underlying the world's best selling drug, AbbVie's Humira®. Despite a non-optimal starting position, AbbVie has established an extensive portfolio to fend off biosimilar competition. This article is the first part of a trilogy that discusses IP issues related to anti-Tumor Necrosis factor α (TNFα) biologics.

The Impact of the Entry of Biosimilars: Evidence from Europe

Biologic drugs (therapeutic proteins or “large-molecule drugs”) represent large and growing share of all drug spending in the United States, accounting for less than 1% of prescriptions filled but nearly 28% of drug spending. Whereas traditional (chemically-synthesized, “small-molecule”) drugs have historically faced price competition from generic drugs after patent expiration, biosimilars – biologic drugs that have been shown to be therapeutically equivalent to an already approved original biologic drug – have only been approved in the United States since 2015. Europe has had biosimilar entry since 2006. This paper considers how competition from biosimilars may impact the U.S. biosimilar market by examining data from the first eight years of biosimilar competition in 23 European countries. A major contribution of this project is the completion of a detailed survey, allowing us to precisely characterize European biologic drug procurement institutions over time. Using data from three classes of biosimilar drugs, we analyze how market features and public policies predict entry, market prices, and penetration of biosimilars. We find significant heterogeneity across countries and drug classes in all of these outcomes. While we observe that effective buyer institutions (in particular, committed tenders) are associated with increased biosimilar entry and penetration, price patterns are more difficult to glean from the available data. Our estimates can inform ongoing policy discussions on both sides of the Atlantic about the economic implications of biosimilar policies.

Leading Drugs Under Fire

High-priced, big-selling biologic drugs lost a bit of their luster this year as competition from the first biosimilar approved in the U.S. emerged. In September, Sandoz, the generic drug arm of Novartis, launched Zarxio, a copycat version of Amgen’s white-blood-cell stimulant Neupogen. Zarxio may be the first, but it certainly isn’t the last. When granting approval in March, the Food & Drug Administration indicated that more biosimilars were “on the way.” At least five versions of four products await U.S. approval, and more than 50 are in development. “Biosimilars are likely to create greater competition in the medical marketplace,” said Leah Christl, FDA’s associate director for therapeutic biologics. She sees them as new, lower-priced alternatives to existing products. Indeed, biosimilar competition is expected to reduce U.S. prices by as much as 35% on the basis of experiences in Europe, Canada, Japan, and Australia, where dozens of biosimilars have been sold ...

Biosimilar competition in the United States: statutory incentives, payers, and pharmacy benefit managers.

Widespread adoption of generic medications, made possible by the Hatch-Waxman Act of 1984, has contained the cost of small-molecule drugs in the United States. Biologics, however, have yet to face competition from follow-on products and represent the fastest-growing sector of the US pharmaceutical market. We compare the legislative framework governing small-molecule generics to that which regulates follow-on biologics, and we examine management tools that are likely to be most successful in promoting biosimilars' adoption. The Biologics Price Competition and Innovation Act established an abbreviated pathway for follow-on biologics, but weak statutory incentives create barriers to entry. Many authors have raised concerns that competition under the biologics act may be weaker than that posed by small-molecule generics under Hatch-Waxman, in part because of legislative choices such as the absence of market exclusivity for the first biosimilar approved and a requirement that follow-on manufacturers disclose their manufacturing processes to the manufacturer of the reference product. Provider skepticism and limited competition from biosimilars will challenge payers and pharmacy benefit managers to reduce prices and maximize uptake of follow-on biologics. Successful payers and pharmacy benefit managers will employ various strategies, including tiered formularies and innovative fee schedules, that can control spending by promoting uptake of biosimilars across both the pharmacy and medical benefits.

Biosimilar competition: lessons from Europe

Grabowski and colleagues analyse the European market uptake of biosimilar versions of two major therapeutic biologics — epoetin alfa and filgrastim — and discuss the implications for the future development of the market for biosimilars.

Are biosimilars the next tool to guarantee cost-containment for pharmaceutical expenditures?

Biological medicines contain a biological substance that is produced by or derived from a living organism. The active substances of biologicals are usually larger and more complex than those of chemically derived medicines (non-biological medicine). Biologicals are used for the treatment of chronic and life-threatening diseases such as cancer, multiple sclerosis and rheumatoid arthritis. Treatment with biologicals is usually expensive and represents ever-increasing pharmaceutical expenditures for the third-party payer. In analogy with the introduction of generics for chemically derived medicines, the expiration of patents of the first biological medicines opened new hopes for affordable copies and increased competition. The replicate versions of a biological medicine “the so-called biosimilars” are available on the European market since 2006, 2007 and 2008, for growth hormone, erythropoiesis-stimulating agents and granulocyte-colony stimulating factors, respectively. In June 2013, the Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorisations for the first two monoclonal antibody biosimilars (infliximab). Most of the available literature on biosimilars has focused on the critical analysis of their specific market authorization procedure. Before 2010, almost no literature addressed theoretical or empirical questions on biosimilar competition and its subsequent impact on uptake and price erosion. This editorial looks at these issues and provides an overview on economic aspects of the new biosimilar competition.

White paper: An outlook on U.S. biosimilar competition

The pharmaceutical industry is experiencing change in ways it hasn't ever before. One topic at the center of all of these changes is the U.S. biosimilars market. This report will provide updates and changes associated with biosimilar regulations in the U.S. Additionally, the paper will identify requirements for success, and the likely early entrants in the U.S. market.

Can next-generation antibodies offset biosimilar competition?

With the first biosimilar version of a monoclonal antibody now under regulatory review in the European Union, which R&D strategies are innovators relying on to counteract competition?