To date, no consensus exists among stakeholders about switching patients between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in ...clinical practice. This study synthesizes the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes. A total of 178 studies, in which switch outcomes from a RP to a biosimilar were reported, was identified. Data were derived from both randomized controlled trials and real‐world evidence. Despite the limitations stemming from a lack of a robust design for most of the studies, the available switching data do not indicate that switching from a RP to a biosimilar is associated with any major efficacy, safety, or immunogenicity issues. Some open‐label and observational studies reported increased discontinuation rates after switching, which were mainly attributed to nocebo effects. Involvement of the prescriber in any decision to switch should remain and attention should be paid to the mitigation of a potential nocebo effect.
Biologic drugs are highly complex molecules produced by living cells through a multistep manufacturing process. The key characteristics of these molecules, known as critical quality attributes ...(CQAs), can vary based on post-translational modifications that occur in the cellular environment or during the manufacturing process. The extent of the variation in each of the CQAs must be characterized for the originator molecule and systematically matched as closely as possible by the biosimilar developer to ensure bio-similarity. The close matching of the originator fingerprint is the foundation of the biosimilarity exercise, as the analytical tools designed to measure differences at the molecular level are far more sensitive and specific than tools available to physicians during clinical trials. Biosimilar development, therefore, has a greater focus on preclinical attributes compared with the development of an original biological agent. As changes in CQAs can occur at different stages of the manufacturing process, even small modifications to the process can alter biosimilar attributes beyond the point of similarity and impact clinical effectiveness and safety. The manufacturer's ability to provide consistent production and quality control will greatly influence the acceptance of biosimilars. To this end, preventing drift from the required specifications over time and avoiding the various implications brought by product shortage will enhance biosimilar integration into daily practice. As most prescribers are not familiar with this new drug development paradigm, educational programmes will be needed so that prescribers see biosimilars as fully equivalent, efficacious and safe medicines when compared with originator products.
Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and ...biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other patient groups, or that the biologic therapy can be moved to an earlier line of treatment. Cost savings from biosimilars can be used to increase patient access to therapy or to increase the number of healthcare professionals. Finally, competition between off-patent biologics and biosimilars may stimulate an innovation in the formulation and development of next-generation biologics. Our paper illustrates that the benefit of off-patent biologics and biosimilars is not restricted to cost savings, but that these medicines may contribute to an expansion of medical treatment options for patients, hence concomitantly contributing to the long-term sustainability of the healthcare system. This review provides a broader view for clinical and economic decision makers and healthcare professionals on the added benefits of off-patent biologics and their use in clinical practice.
Biosimilars are highly similar versions of originator biological medicines, which are approved according to the same standards of pharmaceutical quality and have comparable efficacy and safety in ...patients. Biosimilars offer important benefits to society as their market introduction has been shown to reduce costs and increase patient access to important and often expensive biological therapies. Currently, biological medicines account for approximately 40% of total pharmaceutical expenditure in Europe, and this share is projected to further rise over coming years. As such, the introduction of biosimilars to the market is an essential and necessary way to manage this growing segment and improve the affordability and accessibility of biological medicines for patients and our healthcare systems. Here, Barbier and Vulto discuss the challenging factors for the adoption of innovations in medicine, and biosimilars in particular.
Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe.
The aim of this article is to provide ...an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake.
An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake.
In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution.
Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Little is known about market access to biosimilars from a health economic perspective, except for studies that compute the budget impact of biosimilar use.
Areas covered: This ...comprehensive health economic guide to the market access of biosimilars focuses on the role of biosimilars in pharmaceutical innovation and competition, the objective of biopharmaceutical policy, the budget impact of biosimilars, and the cost-effectiveness of biologic therapy in the presence of biosimilars.
Expert opinion: We argue that the objective of biopharmaceutical policy in a health system should be to create a competitive and sustainable market for off-patent reference biologics, biosimilars, and next-generation biologics that makes biologic therapy available to patients at the lowest cost. Market access of biosimilars can contribute to this objective as a result of the lower price of biosimilars and price competition with alternative therapies. The resulting improvement in the cost-effectiveness of biologic therapy needs to be accounted for by revisiting reimbursement decisions and conditions. When examining the cost-effectiveness of biologic therapy following patent expiry, stakeholders need to consider residual uncertainties at the time of biosimilar marketing authorization, the nocebo effect, market entry of a second-generation reference biologic with a different administration form than the biosimilar, and value-added services.
Background
Despite the benefits offered by biosimilars in terms of cost savings and improved patient access to biological therapies, and an established regulatory pathway in Europe, biosimilar ...adoption is challenged by a lack of knowledge and understanding among stakeholders such as healthcare professionals and patients about biosimilars, impacting their trust and willingness to use them. In addition, stakeholders are faced with questions about clinical implementation aspects such as switching.
Objective
This study aims to provide recommendations on how to improve biosimilar understanding and adoption among stakeholders based on insights of healthcare professionals (physicians, hospital pharmacists, nurses), patient(s) (representatives) and regulators across Europe.
Method
The study consists of a structured literature review gathering original research data on stakeholder knowledge about biosimilars, followed by semi-structured interviews across five stakeholder groups including physicians, hospital pharmacists, nurses, patient(s) (representatives) and regulators across Europe.
Results
Although improvement in knowledge was observed over time, generally low to moderate levels of awareness, knowledge and trust towards biosimilars among healthcare professionals and patients are identified in literature (
N
studies = 106). Based on the provided insights from interviews with European experts (
N
= 44), a number of challenges regarding biosimilar stakeholder understanding are identified, including a lack of practical information about biosimilars and their use, a lack of understanding about biosimilar concepts and a lack of knowledge about biologicals in general. Misinformation by originator industry is also believed to have impacted stakeholder trust. In terms of possible solutions and actions to improve stakeholder understanding, broad support exists to (1) organize initiatives focussed on explaining the rationale behind biosimilar concepts and the approval pathway, (2) invest in education about biologicals in general, (3) develop clear and one-voice regulatory guidance about biosimilar interchangeability and switching across Europe, (4) disseminate real-world clinical biosimilar (switch) data, (5) share biosimilar experiences by key opinion leaders and among peers, (6) provide practical biosimilar product information, (7) provide guidance about biosimilar use, (8) actively counterbalance misinformation and organize information initiatives by neutral entities, (9) organize multi-stakeholder informational and educational efforts, aligning information between involved stakeholder groups and (10) design initiatives in a way that ensures active information uptake. Furthermore, interviewees argue that governments should be proactive in these regards.
Conclusions
This study argues in favour of a structural, multi-stakeholder framework at both European and national level to improve stakeholder biosimilar understanding and acceptance. It proposes a number of actionable recommendations that can inform policy making and guide stakeholders, which can contribute to realizing healthcare system benefits offered by biosimilar competition.
The monoclonal antibody trastuzumab (Herceptin®), which targets the human epidermal growth factor receptor 2 (HER2), is approved for the treatment of early breast and advanced breast and gastric ...cancer in which HER2 is overexpressed. Several biosimilar versions of trastuzumab are expected to enter the European market over the course of 2018 and 2019. The biosimilar development pathway consists of a comprehensive comparability exercise between the biosimilar candidate and the reference product, primarily focussing on data from analytical studies. Clinical studies for biosimilar candidates follow a different design to those for a new biological, as the aim is not to independently establish clinical benefit, but to confirm biosimilarity between the two agents. The different trastuzumab biosimilar candidates have followed diverse pathways in their clinical development, with differences in clinical trial design (equivalence or non-inferiority design), patient population (those with metastatic or early breast cancer) and endpoint (overall response rate or pathological complete response). These differences in approach in phase 3 testing must be viewed in the totality of evidence demonstrating biosimilarity. Adequate information on the biosimilar approval pathway, the nature of the biosimilarity exercise and how the clinical development of a biosimilar is tailored to meet the licensing requirements can help informed decision making in clinical practice.
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