Aim: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. Methods: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. Results: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). Conclusion: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.

In recent years, the development of follow-on biological products (biosimilars) has received increasing attention. The dissertation covers statistical methods related to three topics of Non-inferiority (NI), Bioequivalence (BE) and Equivalence in demonstrating biosimilarity. For NI, one of the key requirements is constancy assumption, that is, the effect of reference treatment is the same in current NI trials as in historical superiority trials. However if a covariate interacts with the treatment arms, then changes in distribution of this covariate will result in violation of constancy assumption. We propose a modified covariate-adjustment fixed margin method, and recommend it based on its performance characteristics in comparison with other methods. Topic two is related to BE inference for log-normal distributed data. Two drugs are bioequivalent if the difference of a pharmacokinetics (PK) parameter of two products falls within prespecified margins. In the presence of unspecified variances, existing methods like two one-sided tests and Bayesian analysis in BE setting limit our knowledge on the extent that inference of BE is affected by the variability of the PK parameter. We propose a likelihood approach that retains the unspecified variances in the model and partitions the entire likelihood function into two components: F-statistic function for variances and t-statistic function for difference of PK parameter. The advantage of the proposed method over existing methods is it helps identify range of variances where BE is more likely to be achieved. In the third topic, we extend the proposed likelihood method for Equivalence inference, where data is often normal distributed. In this part, we demonstrate an additional advantage of the proposed method over current analysis methods such as likelihood ratio test and Bayesian analysis in Equivalence setting. The proposed likelihood method produces results that are same or comparable to current analysis methods in general case when model parameters are independent. However it yields better results in special cases when model parameters are dependent, for example the ratio of variances is directly proportional to the ratio of means. Our research results suggest the proposed likelihood method serves a better alternative than the current analysis methods to address BE/Equivalence inference.

Consumption of similar biological medicinal products (biosimilars) in the Czech Republic Author: Kristýna Vlachová Supervisor: PharmDr. Pavel Horký, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction: Biological treatment is a modern alternative to chemotherapeutics especially in patients with difficult-to-treat diseases of autoimmune origin, as well as patients with other diseases. Biosimilars are biological medicinal products similar to the original biologics. They are increasingly used in a wide range of indications. A new biosimilar drug is registered every year, as soon as the patent protection of the original biologics expires. The assumption is that the consumption of biosimilars and biologists in the Czech Republic will increase. The question is to what extent it will increase and what is the market share of biosimilars. Objective: The aim of the diploma thesis was to analyze the consumption of biosimilar epoetin, adalimumab, infliximab and etanercept in the Czech Republic in 2010-2020. Methods: A retrospective analysis of the consumption of biosimilars epoetin, adalimumab, infliximab and etanercept was performed from 1. 1. 2010 to 31. 12. 2020. The selection of specific biosimilars was made on the basis of their wide...

Après les médicaments génériques, copies de médicaments d’origine chimique, c’est désormais le marché des médicaments biologiques qui s’ouvre à la concurrence de « copies » avec les bio-similaires. De nombreuses incertitudes demeurent concernant l’essor de ce marché aujourd’hui émergent et la capacité des bio-similaires à entrer en compétition avec les autres bio-médicaments innovants.Comme dans le cas des génériques, l’objectif avec les bio-similaires est d’assurer un accès optimal et équitable des patients à des traitements aussi efficaces et sûrs d’utilisation que leurs médicaments de référence, mais à des coûts sensiblement moindres. Suite à l’analyse des premières expériences avec ces produits dans l’Union européenne et au Japon, des limites des politiques mises en place pour encourager leur utilisation et des écueils au développement de ce marché, nous proposons des recommandations pour la construction d’une politique des bio-similaires ambitieuse et cohérente en France. / After generics, which are copies of chemical medicines, "copies" of already patented biologics (biosimilars) are entering the biologics market and competing with their originators. Many uncertainties remain regarding the development of this newly emerging market, and the ability of biosimilars to compete with other innovative biologics. As in the case of generics, the objective with biosimilars is to ensure optimal and equitable patient access to treatment as effective and safe to use as their originators, but at significantly lower costs. Following the analysis of the first experiences with these products in the European Union and Japan, we have noted the limits of existing policies to encourage their use as well as noting pitfalls in the development of this market. To remedy these problems, we make recommendations for the construction of an ambitious and coherent policy for biosimilars in France.

The health care industry’s involvement with biosimilar policies suggests that building coalitions and reducing opposition are critical factors for interest group success. As government decision-makers wrestle with how to handle a perplexing category of prescription drugs, companies and patient groups alike receive ample opportunities to contribute to the policymaking process. When stakeholders in the biosimilar arena – including manufacturers, physicians, and patients – unite, we see that the United States government takes steps toward fixing the policy problem. This occurred most recently with policies about biosimilar drug coverage under Medicare Part D and reimbursement under Medicare Part B. In both cases, stakeholders took a united stance and consequently faced no opposition. On the contrary, internal industry disputes between brand and biosimilar manufacturers about patent exclusivity laws and interchangeability rules revealed the nuances of biosimilar policy and the challenge that regulators face when they receive mixed messages. Across all of their efforts, biosimilar stakeholders pursued numerous strategies which may have contributed to their successes. They focused on niche issues and used their lobbying expertise to actively submit comments, testify in hearings, and meet with government officials; however, the differentiating tactic between the industry’s successes and failures was whether they formed coalitions. By coming together, stakeholders lowered their chances of facing opposition. A closer analysis of the politics of biosimilars illustrates that when they present a united front to lawmakers, interest groups reduce the likelihood of opposition and successfully influence policy change.

Access to bevacizumab, an important component of oncology treatment regimens, may be limited. This survey of oncologists in the US (n = 150), Europe (n = 230), and emerging markets (EM: Brazil, Mexico, and Turkey; n = 130) examined use of and barriers to accessing bevacizumab as treatment of advanced solid tumors. We also assessed the likelihood that physicians would prescribe a bevacizumab biosimilar, if available. Bevacizumab was frequently used as early-line therapy in metastatic colorectal cancer, metastatic non-squamous non-small-cell lung cancer, and metastatic ovarian cancer (all markets), and as a second-line therapy in glioblastoma multiforme (US, EM). A greater percentage of EM-based physicians cited access-related issues as a barrier to prescribing bevacizumab versus US and EU physicians. Lack of reimbursement and high out-of-pocket costs were cited as predominant barriers to prescribing and common reasons for reducing the number of planned cycles. Overall, similar to 50% of physicians reported they "definitely" or "probably" would prescribe a bevacizumab biosimilar, if available. Efficacy and safety data in specific tumor types and lower cost were factors cited that would increase likelihood to prescribe a bevacizumab biosimilar. A lower cost bevacizumab biosimilar could address the unmet needs of patients and physicians worldwide, and may have the greatest impact on patient outcomes in EM.

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. Biosimilars may be viewed as a “pure” or distinct type of process innovation completely separate from product innovation due to the Regulatory requirements and this novel phenomenon allows, perhaps for the first time, process innovation to be studied independently from product innovation. This phenomenon is researched using the competitive dynamic Awareness-Motivation-Capability (AMC) model structure. Since biosimilars are still relatively new, the impact of the biosimilars from a practical and academic viewpoint is emerging and in particular within the US market. This research creates a biosimilar model and metrics, filling a current gap in the literature, and quantitatively evaluates the actions that firms face regarding entering into the biosimilars market due to key metrics such as patent / portfolio risk, prior biologics or generic experience, strength of the R&D pipeline, and the firm’s R&D intensity. The biosimilar construct due to the strict regulatory pathway definition provides this unique and novel opportunity to study process innovation and the impact on competitive dynamics without the interference of product innovation. This research is anticipated to contribute to the practical and academic understanding of process innovation via the biosimilar phenomenon and the competitive dynamics of market entry as well as to promote further managerial research into this area of biosimilars. / Business Administration/Strategic Management

Aim: Biologicals are jointly responsible for growing healthcare expenditures due to their innovation, patent protection, and the increasing number of indications they are used for. The aim of the study was to investigate how costs and prescription volumes of several biologicals developed in a collective of insured persons in statutory health insurance (SHI) and private health insurance (PHI) in Germany over a period from 2016 to 2020. Subject and methods: Primary outpatient prescription data of pharmaceuticals from an SHI and a PHI collective was used focusing on the monoclonal antibodies adalimumab, infliximab, rituximab, and trastuzumab, as well as the differences between their reference drugs and biosimilars. Results: Total prescription volumes of the anti-rheumatic drugs increased while those of the oncologicals decreased. Prescriptions for reference drugs fell in all cases, particularly after the market launch of the first biosimilars. However, while the decline in prescriptions of adalimumab and infliximab in PHI occurred later and more slowly than in SHI, the trend for rituximab and trastuzumab was almost parallel in both systems. In most cases, costs developed in line with prescriptions. Market competition and statutory control mechanisms had a positive impact on overall costs. Conclusion: Statutory control mechanisms such as prescription target quotas and reference price groups in SHI are effective for the drugs investigated. Nevertheless, biosimilar rates in SHI and PHI are not as far apart as the generics rate. For more expensive active substances, a switch to the cheaper biosimilars is more likely than for comparatively cheaper drugs.

隨著人口增長以及人口老化速度加劇，全球藥品消費需求快速成長。生物藥品因其具有針對特定疾病之專一性，在治療病毒性肝炎、癌症及後天免疫缺乏症候群（Acquired Immunodeficiency Syndrome，AIDS）等重大疾病上擁有相當大的發展潛力。除了積極研發全新生物藥品之外，我國生技製藥廠商亦將注意力放到生物相似性藥品的研發上。 但因我國藥品內需市場規模較小，一旦成功研發出生物相似性藥品，若無法將其外銷至海外市場，恐不能弭平鉅額的前期投入。而進入國際市場之際，倘若未制定適宜的進入策略，卻又極可能會以失敗收場。 基於生物相似性藥品本身之特性與法律上之定義，其研發藥廠在進入市場的順序上係處於後進者之地位。但為了成為早期追隨者而搶占部分先驅者優勢，廠商必須選擇恰當的進入模式及進入時機並適時的調整之。而進入障礙對於進入策略之擬定有相當大的影響，尤其以生物相似性藥品市場而言，影響最為深刻的是制度性的進入障礙。 本研究以全球前二大藥品市場─美國、中國大陸為標的，探討我國生物相似性藥品研發廠商進入海外生物相似性藥品市場時，所需跨越的制度性進入障礙可能為何？其他跨國性藥廠在面臨上述制度性進入障礙時，係採取何種因應方法，以及如何調整其進入策略？並從中總結出，對於我國生物相似性藥品研發廠商而言，較為可行的市場進入策略。 經研究分析後，本研究認為，生物相似性藥品市場的制度性進入障礙係來自於東道國的保護主義、專利相關法規與解決專利爭議之機制有所缺漏或偏頗，以及藥品上市審查及藥價管理相關法律規範過於嚴苛或過於鬆散。 而跨國性藥廠因有較充裕的資金及專利訴訟經驗，因此在面對因專利所形成之制度性進入障礙時，可以訴訟或法定行政程序等合法方式克服該專利障礙。對於藥品上市審查法規之要求，則可透過加大投資以求符合法規標準。至於東道國的保護主義，則多藉由與當地企業進行合作、成立合資企業等方式，突破該進入障礙。 因我國生物相似性藥品研發廠商之規模較小，較難獨自克服各生物相似性藥品市場的制度性進入障礙，所以在進入策略上，本研究建議，可積極尋求與原廠或國際生物相似性藥品研發廠商合作，致力於發展全新生物藥品。或是透過兩岸合作研發，於奠定一定基礎後，進一步開拓生物相似性藥品的海外市場。

No description available.