The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases.
ABSTRACT: 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.
Project description:Biologic therapy, such as those that target tumor necrosis factor (TNF) signaling, has proven to be an efficacious method of treatment for patients with inflammatory bowel disease (IBD) with regards to symptom management and mucosal healing. However, the rising prevalence of IBD worldwide and the ever-increasing burden of biologic pharmaceuticals in the health care industry is alarming for insurance companies, clinicians, and patients. The impending patent expiry and the relatively high costs of biologics, particularly anti-TNF agents, have paved the way for biosimilar development for IBD. The United States Food and Drug Administration defines a biosimilar as a biological product that is highly similar to its reference medicinal product, with no clinically meaningful differences in terms of safety, purity, and potency. The hope with biosimilars is that their entry into the market will be able to drive competition between pharmaceutical companies to reduce prices like that of the generic market, and that access to appropriate biologic treatments for IBD patients is increased in the long-term. Yet, there are challenging issues such as indication extrapolation and interchangeability that are still being debated in the field of IBD and must be addressed in future issued guidance. This review will discuss the issues and implications concerning the use of biosimilar therapy for IBD.
Project description: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.
Project description:As patents on many high-selling biological medicines are expiring, non-innovator versions, such as biosimilars, may enter this multi-billion dollar market. This study aims to map patents and patent applications for innovator as well as biosimilar monoclonal antibodies in Europe, and investigates legal challenges associated with patenting the innovator product and alleged infringing activities, focusing on consequences for biosimilar developers. Via an exploratory literature review in PubMed and a database analysis in Darts-ip, Derwent Innovation, and Espacenet, an overview of basic patents and exclusivity rights for some of the best-selling biologicals is given, supplemented with a detailed analysis of patents taken during the medicine's life cycle via three specific case studies (trastuzumab, bevacizumab, cetuximab). Case law was used to determine which patents were viewed by biosimilar developers as blocking market entry. For the selected monoclonal antibodies, the key protection instruments appeared to be the basic patent and the additional protection provided by a supplementary protection certificate. We observed that additional patents filed after the basic patent are hard to obtain and often insufficient in blocking market entry of biosimilars, but can in some cases be a substantial hurdle for biosimilar developers to overcome in patent litigation cases or to invent around, creating uncertainty on the launch date of a biosimilar on the market. These hurdles, however, seem to be surmountable, given that many cases were won by biosimilar developers. Also, biosimilars can be protected by filing new patents and these mainly pertain to new formulations.
Project description:Monoclonal antibody biologic therapies, introduced nearly 20 years ago, revolutionized the treatment of inflammatory bowel disease (IBD) and are now well established as the most effective agents available. As the first of these biologic agents starts to come off patent, biosimilar agents have emerged as alternatives to originator drugs. The unique drug development and manufacturing processes involved in the creation of biologic agents pose distinct regulatory challenges compared to generic formulations of conventional medications. Reductions in medication costs have been proposed to be a major benefit of biosimilar therapies; however, there are concerns regarding the adequacy of the existing regulatory process and data requirements for biosimilar therapy approval, as well as the true bioequivalence of these agents. Infliximab biosimilars for the treatment of IBD have been available in Europe and Asia for a few years and are expected to become available in the United States within the next 1 to 2 years. This article reviews biosimilar therapies and the current data with respect to IBD.
Project description:While biosimilars of low molecular-weight biologics such as G-CSF have been available in Europe since 2006, biosimilars of monoclonal antibodies (mAbs) have only become available in the last year. Unlike G-CSF, mAbs are large and complex and often play a direct role in the survival of patients with life-threatening illnesses such as breast cancer. Several biosimilars are currently under development for the treatment of breast cancer, and the use of biosimilars in a setting that directly impacts patient survival raises a number of questions. In this review, we discuss the biosimilar mAbs currently in development for the treatment of breast cancer. We provide an overview of the European Medicine Agency guidelines and historic data on the development of biosimilars in order to discuss the development of biosimilar mAbs for breast cancer. Biosimilars offer a highly attractive path toward reducing the cost of medical care and should be pursued with great interest. However, for agents used to treat life-threatening diseases such as cancer, a cautious approach must be taken to ensure that there is no negative impact on patient care. Clinical trials for biosimilar mAbs must be carried out in an appropriately sensitive patient population using endpoints that can accurately demonstrate both the similarity of the biosimilar and its efficacy in the indication. Due to the abbreviated approval pathway, rigorous pharmacovigilance must be in place once a biosimilar mAb is approved in order to ensure its long-term safety and efficacy.
Project description:OBJECTIVE:Bevacizumab is an important component in the treatment of various cancers, and despite guidelines recommending its use in both ovarian and cervical cancer, patient access to bevacizumab and other angiogenesis inhibitors is limited. Biosimilars are large, structurally complex molecules that are intended to be highly similar to, and treat the same condition(s) as, an existing licensed or approved (reference) biologic, with no clinically meaningful differences in purity, potency and safety. This article summarizes the role of bevacizumab in the treatment paradigm of ovarian and cervical cancer. We also discuss the potential role of biosimilars to bevacizumab, which may offer more affordable options in the future treatment of gynecologic cancers. METHODS:Literature searches of PubMed and ClinicalTrials.gov databases were conducted. Regulatory and individual pharmaceutical company web pages were also reviewed. Search terms included "biosimilar" and "bevacizumab," and these were used to identify information regarding biosimilar development, reporting results of biosimilar studies or biosimilars in development. RESULTS:At present, four bevacizumab biosimilar candidates are undergoing comparative clinical assessment, with the potential to increase access and offer efficiencies across healthcare systems. CONCLUSIONS:It is anticipated that biologics such as bevacizumab will continue to play a key role in the treatment of an array of gynecologic cancers. Biosimilars to bevacizumab are currently in development and have the potential to increase access to medicines in a variety of settings, including gynecologic cancers.
Project description:The management of inflammatory bowel disease (IBD), a significant cause of morbidity in the United States (US), has been revolutionized over the last two decades by the introduction of biologic therapies. These include antitumor necrosis factor ? (TNF-?) agents. Since 2016, five biosimilar TNF-? inhibitors have been approved by the US Food and Drug Administration (FDA) for use in the treatment of IBD. The FDA has published a series of guidance documents related to the evaluation, licensing, and approval of biosimilars. The aim of this review is to provide an overview of these FDA guidances and the issues associated with biosimilars in the US.
Project description:<h4>Objective</h4>To understand the levels of awareness, usage, and knowledge of biosimilars among patients, caregivers, and the general population in the US and the European Union; perceptions of biosimilars compared to originator biologics; perceived benefits and drawbacks of clinical trials; and whether advocacy groups impact patients' willingness to try a biosimilar.<h4>Methods</h4>An international survey was conducted which contained up to 56 closed-ended (requiring yes/no or ranking answers) and open-ended questions, depending on the population assigned. The survey was divided into distinct sections, including medication-class awareness, usage, and knowledge about biologic and biosimilar therapies; perceptions of clinical trials; and involvement in advocacy groups. Interviews were conducted in adults categorized as: 1) diagnosed: patients with inflammatory bowel disease including Crohn's disease and ulcerative colitis, rheumatoid arthritis, psoriasis, breast cancer, lung cancer, colorectal cancer, or non-Hodgkin's lymphoma; 2) diagnosed advocacy: individuals with these diseases who participated in patient support groups; 3) caregiver: has a loved one with these conditions and is involved in medical decisions; 4) general population: aged 18-64 years, without these conditions. Statistical analyses among groups within a region (US or EU) used column proportions test with a 95% confidence interval.<h4>Results</h4>In all, 3,198 individuals responded. Awareness about biologic therapies was significantly higher in diagnosed, diagnosed advocacy, and caregiver groups (45%-78%) versus general population (27%; P<0.05). Across all groups, awareness of biosimilars was low; only 6% of the general population reported at least a general impression of biosimilars. Awareness was significantly higher in the diagnosed advocacy group (20%-30%; P<0.05). Gaps in knowledge about biosimilars included safety, efficacy, and access to these agents. Respondents had generally positive perceptions of clinical trials, although barriers to participation were identified.<h4>Conclusion</h4>An immediate need exists for patient education about biosimilars and clinical trials to ensure educated and informed decisions are made about biosimilar use.
Project description:Infliximab was the first monoclonal antibody used in the treatment of inflammatory bowel disease (IBD). Over several years, this antitumour necrosis factor (TNF) treatment proved its efficacy in both induction and maintenance therapy. In many cases this biological treatment stopped the progression of the disease, probably also decreasing morbidity and hospitalization rates, and improving patients' comfort. When the patent on infliximab started to expire, the first biosimilar of a monoclonal antibody was introduced onto the pharmacological market. Biosimilar infliximab was studied in rheumatology and proved a high similarity to the reference drug. Based on extrapolation, biosimilars were approved to treat adult and paediatric IBD patients. Biosimilar infliximab, mainly because of its lower cost, has started to be in common use in Europe. The first studies have shown a similar efficacy and safety profile in comparison with reference drug. Biosimilar infliximab is raising hopes for improving the availability of this effective treatment.
Project description:<h4>Introduction</h4>The Biosimilars Forum conducted a survey through an independent organization from November 20, 2015 to January 4, 2016 in order to assess current levels of awareness, knowledge, and perceptions of biosimilars among US specialty physicians who already prescribe biologics. The survey was intended to provide a baseline level of knowledge about biosimilars and will be repeated in 2-3 years in order to monitor trends over time.<h4>Methods</h4>A 19-question survey was created by the Biosimilars Forum and was administered by an independent third party.<h4>Results</h4>Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including dermatologists, gastroenterologists, hematologist-oncologists, medical oncologists, nephrologists, and rheumatologists.<h4>Conclusions</h4>The results of this survey highlight a significant need for evidence-based education about biosimilars for physicians across specialties. Five major knowledge gaps were identified: defining biologics, biosimilars, and biosimilarity; understanding the approval process and the use of "totality of evidence" to evaluate biosimilars; understanding that the safety and immunogenicity of a biosimilar are comparable to the originator biologic; understanding the rationale for extrapolation of indications; and defining interchangeability and the related rules regarding pharmacy-level substitution.<h4>Funding</h4>Biosimilars Forum.