Efficacy Of Biosimilars Research Articles

Biosimilar Bias: A Barrier to Addressing American Drug Costs

Forty percent of spiraling US drug costs are based on a mere two percent of all drugs –biologic drugs (biologics) made from living cells that are administered by injection or infusion. These costs will continue to balloon as new biologics are approved; the recently approved Alzheimer’s drug is expected to result in a 50% increase in Medicare spending and cost individuals 40% of their annual income. These drugs are expensive because they cannot be mass-produced, and their cost places important treatments for conditions such as arthritis (Humira) and cancer (Herceptin) out of reach for many Americans. Fortunately, just as there are generic versions of brand name pills, there are lower cost biosimilars of original biologics allowed by an expedited regulatory approval process that lowers the costs of obtaining regulatory approval. However, US adoption of biosimilars is minimal, in stark contrast to widespread use of generic drugs, and despite a decade of safe biosimilar use in other countries. This Article provides the first comprehensive explanation of how US laws, industry actions, and cognitive biases work together to impede US biosimilar use. This Article argues that doctors and patients currently have unfounded misperceptions concerning the safety and efficacy of biosimilars based on misinformation propagated by companies that builds upon an existing cognitive bias against cheaper drugs. Not only does this keep drug costs high, but it also creates worse health outcomes for patients since studies show unfounded misperceptions have negative physical manifestations. Although there is a similar misperception against generic drugs, structural differences in terms of regulatory laws and insurance coverage exacerbate biases against biosimilars. For example, US regulatory laws have created an additional regulatory designation for biosimilars to be substituted without doctor intervention; this is contrary to the process for generics where there is no additional federal designation required for substitution. After revealing the existence and extent of bias against biosimilars, this Article proposes solutions to effectively promote biosimilar use. It suggests a multi-pronged approach to encourage biosimilar use that includes legal changes to support biosimilar substitution, education to specifically tackle biases, and financial incentives to encourage biosimilar use. These proposals are especially timely since the FDA just approved the first biosimilar that can be substituted for the comparable brand at pharmacies, more than a decade after the biosimilar pathway was created, suggesting that the time is ripe to address systemic issues. Moreover, addressing these barriers to biosimilar use would not only expand access to treatment, but also save the US an estimated $50 billion in the next decade.

Biosimilars in inflammatory bowel disease.

The advent of biologics has changed outcomes in many chronic conditions, including inflammatory bowel disease (IBD). Biologics have been used for the induction and remission of ulcerative colitis and Crohn's disease for almost two decades and are effective in patients who used to fail conventional treatment with steroids, immunomodulators. The use of biologics in the treatment of IBD has increased over the last few years, partly due to the rise in its incidence and the use of biologics as a first-line treatment in severe disease as well as in complicated diseases like penetrating/fistulating Crohn's disease. However, their use is associated with a significant burden to the society with respect to healthcare costs, resulting in the premature discontinuation of therapy in some patients, leading to exacerbations and complications. The introduction of biosimilars a decade ago seems to be a promising approach to reducing the costs related to therapy. Since their introduction, numerous studies conducted in adults and some in children show the efficacy of biosimilars with a similar side-effect profile to biologics. This review discusses the history of biosimilars in the treatment of IBD, enumerates several such studies and discusses the possibility of using biosimilars in the future.

PGI2 Quantitative Evaluation to Efficacy and Safety of Biosimilar of Infliximab in Inflammatory Bowel Diseases: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Because there are no clinical trials conducted to compare the safety and efficacy of the biosimilar of infliximab to the previous standard of care, we performed a Bayesian Network Meta-Analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of Biosimilar of infliximab in patients with IBD. Electronic searches of PubMed (Medline), EMBASE (Ovid), Scopus, CENTRAL, as well as online material were performed until July 2019 to identify all RCTs evaluating the efficacy or safety of biosimilar versus infliximab and originator infliximab versus placebo in patients with IBD. The outcomes were the pooled rates of clinical response and adverse events. A Bayesian Network Meta-Analysis approach was performed. Five RCTs reporting outcomes in 1,745 patients treated with either biosimilar or originator infliximab were identified. The pooled rates of clinical response among IBD using infliximab and originator infliximab in respect to placebo were 4.19 (95% confidence interval (CI) = 2.49–7.04) and 3.97 (95% CI = 2.374–6.64), respectively. Adverse events did not differ significantly among infliximab and originator infliximab in respect to placebo. No significant difference was found between biosimilar and originator Infliximab in respect to the placebo in terms of efficacy and safety, supporting its use in the treatment of IBD.

P61 Patient perspectives on switching to an infliximab biosimilar in paediatric inflammatory bowel disease (PIBD)

AimTo establish patient perspectives on switching to an infliximab biosimilar, which will enable the PIBD team to improve patient experience during future biosimilar switches.MethodsFamilies of patients receiving treatment with an Infliximab biosimilar (Remsima®) 2 years after switching from the originator (Remicade®) were selected from the active patient database for telephone interview. One family who chose not to switch was also included for interview. A 5-question interview was prepared, which asked parents to rate their overall experience according to a satisfaction rating scale from 1–5. Parents were asked about their knowledge of reasons for switching, if they needed to look up additional information resources and, finally, ways to improve the switching process.Results18 patients were identified, 16 parents were available for interview. 13 parents gave overall positive feedback with satisfaction scores of 4 or 5 on the numerical satisfaction scale. 3 parents were dissatisfied with the switching process, giving scores of 0, 1 and 3. This resulted in an average satisfaction score of 4.1. The majority of satisfied parents had little knowledge of the switch, not remembering details and indicating the switch was best performed this way. Nonetheless, most recognised costs as the reason for switching. The majority of parents did not need to look up additional information resources, 2 parents named The Crohn’s and Colitis Charity and Facebook support groups as useful resources. Two dissatisfied patients requested to switch back to Remicade® therapy due to side effects. The family of the patient who chose not to switch made this decision because Remsima® was not yet available in the United States, where they also received treatment.ConclusionBiosimilar biologics continue to be approved by the EMA as originators come off patent. Efficacy of infliximab biosimilars in paediatric IBD patients is extrapolated from adult rheumatology data, with limited long term outcome data.1 2 Successful switches for NHS trusts lead to financial benefits; these savings allow for NHS investment to enable more patients to be treated.3Patient autonomy and, in paediatrics, parental views must be respected during this switching process. The majority of interviews with parents were positive, re-affirming the process of this switch. Parental perceptions of side effects attributed to Remicade® highlight the importance of discussing realistic outcomes of therapy with both the originator and biosimilar. When questioned, the parent who refused to switch explained that they did not have faith in the efficacy of the biosimilar and had major concerns of treatment failure. A fear of treatment failure may be described as a ‘nocebo’ effect 4 which hypothesises that negative attitudes incur less effective results. Increasing our awareness of patient perceptions on switching biosimilars and monitoring reasons for switch failure will better inform us going forward with future biologic switches.ReferencesDanese S, Fiorino G, Raine T, et al. ECCO position statement on the use of biosimilars for inflammatory bowel disease—an update. J Crohn’s Colitis 2017;11:26–34.de Ridder L, Waterman M, Turner D, et al. Use of biosimilars in paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2015;61:503–508.Healy M, Crook J, Chavda C, et al. P35 An experience of switching paediatric inflammatory bowel disease patients on infliximab therapy to the biosimilar ‘remsima.’Arch Dis Child 2018;103:e1.39–e1.Ordinet J, Day C, Cruz J, et al. The biosimilar nocebo effect? A systematic review of double-blinded versus open-label studies. J Manag Care Spec Pharm 2018;24:952–959.

A Clinical Review of Biosimilars Approved in Oncology.

To summarize and review the clinical data of Food and Drug Administration (FDA)-approved biosimilars for use in treatment of cancer and the current challenges health care institutions face when implementing a newly approved biosimilar. A literature search of the following databases was performed between January 1, 2012, and December 31, 2019: PubMed, Google, and ClinicalTrials.gov. Search terms included the words biosimilar, bevacizumab, rituximab, and/or trastuzumab. Only primary literature on biosimilars with an ongoing or completed phase 3 trial and/or FDA approval were included in the final analysis. Primary literature consisted of peer-reviewed publications, published abstracts, and any results posted on the ClinicalTrials.gov database. Clinical trials of FDA-approved biosimilars for bevacizumab, rituximab, and trastuzumab showed no significant differences with respect to efficacy, safety, and pharmacokinetics when compared with their reference products. The anticipated growth of biologics in oncology and the recent introduction of biosimilars over the past few years have placed a lot of emphasis on biosimilars as a significant source of cost savings for the health care system. Our article compiles and analyzes existing data on biosimilar efficacy, safety, and financial impact. The major concerns of biosimilars revolve around their long-term efficacy and safety. Even with many questions to be answered, biosimilars have the potential for significant cost savings in the US health care system.

Effects of Message Framing on Patients’ Perceptions and Willingness to Change to a Biosimilar in a Hypothetical Drug Switch

Patients often hold negative perceptions toward biosimilars that can create barriers to their uptake. Physicians also report uncertainty in how best to explain biosimilars. The aim of this study was to measure the effect of differently framed explanations on patients' perceptions of and willingness to change to a biosimilar in a hypothetical drug switch. Ninety-six patients with rheumatic diseases taking an originator biologic were randomized to receive 1 of 4 biosimilar explanations: positive framing with and without an analogy, and negative framing with and without an analogy. Willingness to switch to a biosimilar, perceptions about biosimilars, and the effectiveness of the explanation were measured after the information delivery. Positive framing led to more participants being willing to switch (67%) than negative framing (46%). Framing significantly predicted willingness to switch to a biosimilar, with participants in the positive framing group being 2.36 times more willing to switch (P = 0.041). The positive framing group also reported significantly greater perceived efficacy of biosimilars (P = 0.046) and thought the explanation was more convincing (P = 0.030). The analogy did not enhance willingness to switch or increase understanding (P > 0.05). Positive framing can improve perceptions of and willingness to switch to a biosimilar in patients currently taking biologic treatments.

Biosimilars to Antitumor Necrosis Factor Agents in Inflammatory Bowel Disease.

Anti- tumor Necrosis Factor (anti-TNF) agents are the backbone treatment of moderate to severe cases of inflammatory bowel disease. One of the main drawbacks of these agents is the high cost. The introduction of biosimilar products to anti-TNF agents is expected to lower the cost. Health care providers ought to be aware of the available data that addresses the safety and efficacy of biosimilars in IBD patients. This article outlines the current evidence-based data regarding the available biosimilar products, their safety, efficacy and how to deal with patients’ concerns.

Regulation and Challenges of Biosimilars in European Union

Background: Biological products comprise the most complex and diverse types of drugs that are made by living cells. The use of biological products has increased significantly in recent decades and has contributed significantly to improving the efficacy of treatment in many diseases. Patent protection for pharmaceutical products, including biological products, generally expires about 20 years after development. Expiration of patents of biological innovative medicines allows regulatory authorities to approve copies of biological medicines, such as medicines called similar biological products (biosimilar) and to enter in clinical use. Biosimilar products are comparable but not identical with innovator biological products and are not a generic version of the innovator biological product. While biosimilars are subjected to rigorous characterization and clinical trials to demonstrate their safety and efficacy, in the case of biosimilars certain regulatory requirements apply for registration. Biosimilars are very complex and large molecules and minor changes in the manufacturing process can have important implications in their safety and efficacy profiles. To ensure that biosimilar reaches their potential in clinical application, intensive Pharmacovigilance system and risk management plan must be established to demonstrate the true similarity between the biosimilar products and original biological products. Biosimilars are part of the growing sector of the pharmaceutical industry and normally used by human beings since manufacturers of biosimilars face some challenges in regulatory approval and manufacturing of biosimilars in the European Union. Objectives: The current manuscript will provide the information regarding the regulation of biosimilar products with guidelines and challenges faced by manufacturers during approved and manufacturing of biosimilar products in the European Union. This manuscript also provides the status of approved and rejected biosimilars by EMA (European Medicine Agency). Conclusion: Biosimilars may reduce costs when patent protection of biological products expires and compared to the original products, savings are not as large as seen with traditional generics. In the coming years, there will be an increasing number of biological and biosimilar products available on the market, highlighting the need for specific short and long term post-marketing surveillance programs for these medicines. It is essential to understand how the concept of compatibility, interchangeability will be managed and regulated in the future. An important aspect for future a high quality, clinical and non-clinical studies will be conducted to evaluate the safety and efficacy of biosimilars. Scientific guidelines on biosimilar issued by the EMA (European Medicine Agency) that established a process to demonstrate the similarity between a biosimilar product and the innovator reference product.

Observational study of inflammatory arthritis treatment by etanercept originator switched to an etanercept biosimilar.

ObjectivesThe aim of the study was to assess the safety and efficacy of switching an etanercept originator to an etanercept biosimilar in rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis patients.Material and methodsIn 162 patients etanercept originator treatment had been replaced with the biosimilar (Group 1), and in six patients the biosimilar was initiated as the first biological agent (Group 2). The efficacy and safety of the treatment were monitored at 3–6 months.ResultsIn the majority of patients in Group 1 (n = 138) the etanercept biosimilar was well tolerated, whereas in 24 patients a switch back to the originator was required. The loss of efficacy was confirmed in nine patients using clinical scoring system, and nine patients reported subjective loss of efficacy; 13 patients reported adverse events, most often headache (n = 3) and skin lesions (n = 3). In four patients injection site reactions were present. The adverse events (AE) and/or the loss of the biosimilar efficacy were more commonly observed in women, patients with rheumatoid arthritis (especially in those who did not receive methotrexate), and in patients with a previous history of any other biological treatment. In patients in Group 2 the therapy was effective and no adverse events were observed.ConclusionsThe etanercept biosimilar seems to be effective and well-tolerated in the majority of patients. Nevertheless, in some cases, switching from the originator to the biosimilar was associated with AEs or loss of efficacy.

Ask the Hematologist: Safety and Efficacy of Biosimilars for Hematologic Malignancies

Ask the Hematologist: Safety and Efficacy of Biosimilars for Hematologic Malignancies

Maneuvering Clinical Pathways for Crohn's Disease.

Crohn's disease management has changed significantly with increasing use of biologics. We review the recent literature on the clinical management of Crohn's disease and new approaches in selecting and optimizing therapy. Recent studies have addressed the efficacy of proactive anti-TNFα trough level monitoring, the efficacy of biosimilars, and the efficacy and immunogenicity of newer biologics including anti-integrin therapy and anti-IL12/23 therapy. Optimizing anti-TNFα therapy according to trough concentrations correlates with improved remission rates. Patients can be switched from the reference drug to a biosimilar, or vice versa, without a measurable change in efficacy, safety, or immunogenicity. Immunomodulators are effective in decreasing immunogenicity and boosting anti-TNFα drug level. The anti-integrin and anti-IL12/23 therapies are effective as induction and maintenance therapy with low immunogenicity and excellent safety profiles. Patients at high risk for post-operative recurrence should be started on a biologic therapy within 4weeks post-op. Multiple biologic therapies are currently available for treatment of Crohn's disease including anti-TNFα therapy, anti-integrin therapy, and anti-IL12/23 therapy. The choice of first-line therapy should be based on individual risk-benefit analysis, route of administration, and patient preference. Patient with inadequate response should have their trough level checked and therapy optimized. Therapeutic prophylaxis for post-operative recurrence should be based on patient's risk factors for recurrence.

Strategies for Overcoming Barriers to Adopting Biosimilars and Achieving Goals of the Biologics Price Competition and Innovation Act: A Survey of Managed Care and Specialty Pharmacy Professionals.

The Biologics Price Competition and Innovation Act (BPCIA) of 2009, which included pathways for FDA approval of biosimilar products, was designed to promote more affordable, expanded patient access to biologic therapies. Achieving these BPCIA goals depends on overcoming formidable barriers to biosimilar adoption. Managed care and specialty pharmacy professionals are uniquely qualified to inform initiatives to address these barriers. To assess perceptions regarding strategies for overcoming barriers to biosimilar adoption among managed care and specialty pharmacy professionals by conducting a survey study. Invitations to complete the online survey were emailed by the Academy of Managed Care Pharmacy (AMCP) to members and customers and to contacts sourced from a commercial database. In addition to questions on respondent demographics and perceptions of biosimilars, the survey listed 16 strategies for overcoming key barriers to biosimilar adoption. On a 5-point scale, participants rated their opinion on the likelihood that each strategy would have the potential to assist in achieving BPCIA goals. The survey also listed 6 barriers to biosimilar adoption. On a 5-point scale, participants rated their perceived difficulty in overcoming each barrier. The survey concluded with an open-text item that asked participants to list 3 additional strategies for overcoming biosimilar adoption barriers. Response frequencies were calculated to describe participants' ratings of the strategies and barriers. Statistical analyses were conducted to assess whether the ratings differed among respondents grouped by work organization. For the open-text item, we conducted qualitative content analyses to categorize strategies by stakeholder groups that might take primary implementation roles. A total of 300 managed care and specialty pharmacy professionals completed the survey. There was considerable variation in the preferences, policies, and practices regarding biosimilar adoption among respondents' work organizations. Responses to several survey items reflected positive attitudes about the safety and efficacy of biosimilars; for example, 84% agreed or strongly agreed that FDA-approved biosimilars are safe and effective for patients who switch from a reference biologic. Based on pooled percentages for ratings of likely and extremely likely to overcome barriers to biosimilar adoption, the highest-rated strategies were for prescriber education about evidence from switching studies (91%) and FDA guidance on pharmacy-level substitution of reference biologics with biosimilars (90%). The lowest-rated strategies were for requiring therapeutic drug monitoring for patients who switch to biosimilars (39%) and using quotas to incentivize providers to prescribe biosimilars (40%). For the qualitative analysis, the highest numbers of respondents' suggested strategies indicated primary implementation roles of biosimilar manufacturers (40%), the federal government (26%), and managed care organizations (15%). Reflecting the unique knowledge, perspectives, and practices of managed care and specialty pharmacy professionals, the study findings are relevant to informing and advancing initiatives for achieving BPCIA goals. The survey study reported in this article was part of a continuing education program funded by an independent educational grant, which was awarded by Sandoz, a Novartis Division, to PRIME Education. The Academy of Managed Care Pharmacy (AMCP) received grant funding from PRIME to assist in developing the survey and writing the manuscript. The grantor had no role in the study design, execution, analysis, or reporting. Greene and Pardo are employed by PRIME. Singh and Carden are employed by AMCP. Greene, Singh, Carden, and Pardo have no other disclosures. Lichtenstein received an honorarium from PRIME for serving as faculty for the continuing education program and has been a consultant for Pfizer, Cellceutix, and Merck.

Efficacy of Biosimilars in Psoriasis

Biologic therapies have revolutionized the treatment of moderate-to-severe psoriasis, and several biologic agents are currently available to patients. However, the high cost associated with these drugs contributes to the underutilization of biologics and the resultant undertreatment of disease. In recent years, biosimilars have been developed for several of the commonly used biologic agents, with reported similar efficacy and safety profiles to the original agents. They are also somewhat less costly than the original biologic agents that they are similar to. Despite this, many dermatologists are still skeptical of biosimilars for a variety of reasons. It is important for dermatologists to familiarize themselves with the emerging safety and efficacy data for the biosimilar agents, so as to provide patients with safe, efficacious, and potentially affordable treatment options as biosimilars become available over the next several years. In this article, we set out to review available data regarding biosimilar medications in the treatment of psoriasis. A literature review was performed utilizing the PubMed database. The results of these studies indicate that biosimilars have a high degree of similarity regarding safety and efficacy when compared to their originator biologics for the treatment of psoriasis.

A randomized double-blind parallel-group phase III study to compare the efficacy and safety of NI-071 and infliximab reference product in Japanese patients with active rheumatoid arthritis refractory to methotrexate

Objectives: This study aimed to demonstrate the equivalence of NI-071, an infliximab biosimilar (BS), and the infliximab reference product (RP) for treating Japanese patients with active rheumatoid arthritis (RA) refractory to methotrexate.Methods: In this multicenter two-period phase III study, patients were treated with BS or RP for 30 weeks (Period I) in a randomized double-blind manner and then with BS for the following 24 weeks (Period II). The efficacy and safety of BS and RP were compared.Results: The disease activity score in 28-joint count based on erythrocyte sedimentation rate or C-reactive protein and the American College of Rheumatology 20/50/70-based efficacy profiles of BS were similar to those of RP during Period I (30 weeks) including evaluations at week 14, a critical time point. BS efficacy was maintained throughout the 54-week study period. BS efficacy profile matched the RP profile until week 54 after the drug switch from RP to BS at week 30. The safety profiles of BS and RP were comparable and the long-term safety of BS was confirmed.Conclusion: BS demonstrated equivalent efficacy and safety to RP at treatment weeks 14 and 30, and long-term safety until week 54 in Japanese RA patients.

Comparative efficacy and safety of adalimumab biosimilar (BCD-057) and innovator in patients with psoriasis vulgaris. Results of the BCD-057-2/CALYPSO phase III international, multicenter, randomized double-blind clinical trial

The paper gives the results of the phase III clinical trial of adalimumab (ADA) biosimilar, (BCD-057) (BIOCAD, Russia), which demonstrate the clinical equivalence of the biosimilar to the ADA innovator Humira® in patients with moderate and severe psoriasis.Objective. The BCD-057-2/CALYPSO phase III international, multicenter, randomized double-blind clinical trial of the efficacy and safety of BCD-057 (International Nonproprietary Name (INN): adalimumab, ZAO «BIOCARD», Russia) versus Himura® (INN: adalimumab (OOO «Abbvie») in patients with plaque psoriasis aims to prove the equivalent pharmacokinetics, efficacy, safety, and immunogenicity of these medicines in both direct parallel comparison and subsequent switching from innovator to biosimilar.Patients and methods. The investigation enrolled 346 adult patients diagnosed with moderate to severe plaque psoriasis lasting at least 6 months. After screening, the patients were randomized in a 1:1 ratio into BCD-057 or Humira® groups. At week 24, the patients taking Humira® were re-randomized 1:1 into a group to continue treatment with the ADA innovator or into that to switch to BCD-057. The primary efficacy endpoint was to estimate the proportion of patients who had achieved a 75% improvement in Psoriasis Area and Severity Index (PASI75) at week 16. The secondary endpoints included the assessment of the time course of changes in the skin, nails, degree of itching, and quality of life at weeks 16 and 24. Safety was evaluated from the incidence of treatment-associated adverse events (AEs), cases of severe toxicity (grades 3–4 AEs according to the Common Terminology Criteria Adverse Event (CTCAE) 4.03), cases of early patient withdrawal due to AEs, as well as cases of toxicity potentially associated with the use of tumor necrosis factor-α inhibitors. Immunogenicity was determined using the validated test of patient serum samples for binding antibodies (BAb) and neutralizing antibodies.Results and discussion. The per-protocol population for efficacy evaluation included 342 patients. At week 16, the primary endpoint of PASI75 was shown to be achieved by 62.5% (105/168) and 66.46% (109/164) of the patients in the BCD-057 and Himura® groups, respectively; p=0.45). The difference between the groups in PASI75 responses was 3.22% with 95% confidence interval [-14.25%; 6.32%]. The analysis of additional endpoints revealed no significant differences in the efficacy of the biosimilar and innovator. During 24 weeks of the investigation, treatment-associated AEs were recorded in 31.03 and 25.58% of the patients in the BCD-057 and Humira® groups, respectively (p=0.31). The proportion of patients with BAb detected at 16 weeks of the investigation was 25.44 and 24.07% in the BCD-057 and Humira® groups, respectively (p=0.87).Conclusion. The investigation provided convincing clinical evidence for of the equivalent efficacy, safety, and immunogenicity of BCD-057 and Humira®.

Anti-Tumour Necrosis Factor in Inflammatory Bowel Disease: Inventory and Outlook

Biosimilars have contributed substantially to the evolving therapeutic landscape for inflammatory bowel disease (IBD), enabling healthcare systems to offer access to a broader range of therapies at an affordable price. Despite the increasing confidence healthcare practitioners (HCP) place in the safety and efficacy of biosimilars, uncertainty remains around best practice when switching a patient from a reference product to a biosimilar. This symposium aimed to uncover the importance of a managed switch programme by exploring real-world data from the University Hospital Southampton NHS Foundation Trust, Southampton, UK, and University Hospital Erlangen, Erlangen, Germany. The roles of therapeutic drug monitoring and predictive outcome scoring were discussed based on evidence from the SECURE and the CREOLE studies, respectively. Finally, in light of the recent European Union (EU) approval of adalimumab biosimilars, the future therapeutic landscape and how physicians and patients can make well-informed decisions when multiple versions of the same biologic are available were discussed.

Biosimilars: Italian Medicines Agency takes position.

The Italian Medicines Agency issued a new position paper on biosimilars that clarified several points regarding their correct use. This is a document that has the intent to promote the correct use and prescription of these medicines by answering some of the frequent questions coming from patients and prescribers. The debate surrounding the use of biosimilars is far from being concluded. However, some aspects, such as those regarding the quality, the safety and the efficacy of biosimilars, as well as the possibility of prescribe biosimilars not only to naïve patients naïve, it seems to be well supported. According to the new AIFA's position paper, the prescriber need to be the principal decision makers in the choice between biological and biosimilar. In the future, it will be interesting to check how much these new concepts will be able to influence, in current practice, the correct use of drugs that are presented as an important therapeutic resource for the National Health Service.

Regulatory evaluation of biosimilars throughout their product life-cycle.

The World Health Assembly in 2014 adopted a resolution that recognized the importance of increasing access to biotherapeutic products, of improving their affordability and of ensuring their quality, safety and efficacy. Biosimilars are biotherapeutic products similar to already licensed reference products and are usually developed after patents on the original products have expired. Their introduction into the market is likely to reduce the costs of medicines substantially, thereby improving the availability of treatment for patients. However, there are barriers to market access for biosimilars. This article discusses the factors that give rise to these barriers and explains the importance of regulatory oversight throughout the product life-cycle of biosimilars. The paper also describes the role regulators can play in increasing confidence in biosimilars use by: (i) establishing regulatory oversight of biosimilars throughout their life-cycle, from development to post-licensing oversight, and ensuring that only high-quality, safe and efficacious biosimilars are available on the market; (ii) ensuring regulatory authorities have adequate capacity to assess and monitor the quality, safety and efficacy of biosimilars throughout their life-cycle; and (iii) monitoring the use of biosimilars in public health systems in collaboration with other stakeholders.

American Society of Clinical Oncology Statement: Biosimilars in Oncology.

As many biosimilars come to market in the next several years, their use in oncology will play an important role in the future care of patients with cancer. ASCO is committed to providing education and guidance to the oncology community on the use of biosimilars in the cancer setting; therefore, ASCO has developed this statement to offer guidance in the following areas: (1) naming, labeling, and other regulatory considerations, (2) safety and efficacy of biosimilars, (3) interchangeability, switching, and substitution, (4) value of biosimilars, and (5) prescriber and patient education.

Longitudinal assessment of the impact of multiple switches between a biosimilar and its reference product on efficacy parameters.

Patients, physicians, and health care providers in Europe have more than 10 years of experience with biosimilars. However, there are still debates if switching between a biosimilar and its reference product influences the efficacy of the treatment. In this paper, we address this uncertainty by developing a formal statistical test that can be used for showing that switching has no negative impact on the efficacy of biosimilars. For that, we first introduce a linear mixed-effects model that is used for defining the null hypothesis (switching influences the efficacy) and the alternative hypothesis (switching has no influence on the efficacy). Using this as the foundation of our work, we propose several approaches for testing for changes in the efficacy of the treatment due to switching and discuss the properties of these tests in an extensive simulation study. It is shown that all these methods have advantages and disadvantages and the decision regarding which method is preferred depends on the expectation of a switching assessment. To demonstrate the applicability of the methods in practice, the approaches were applied to the data of the EGALITY study, which compares the reference product Enbrel®(Amgen) with the approved biosimilar Erelzi® (Sandoz).