Abstract: Biosimilars are hypothesized to contribute to lowering health care costs by entering the market at a discounted price compared with their reference biologics. Until recently, only filgrastim biosimilars were available in oncology, but bevacizumab and trastuzumab biosimilars have now been approved, and additional biosimilars are expected to enter the oncology landscape as more biologics lose their patents and market exclusivity. However, biosimilars uptake and commercial success is contingent upon prescribers’ acceptance of their safety and efficacy as well as prescribers’ understanding of the regulatory processes that lead to biosimilars’ approval. Identifying barriers to uptake is essential to develop strategies that increase chances of biosimilars’ success in oncology. To that end, we conducted primary market research study of over 500 US-based hematologists and oncologists. A survey was administered that included questions about reimbursement, regulatory guidelines, and the use of specific biosimilars. Based on the responses, we identified critical educational gaps that need to be addressed by manufacturers and policymakers in order for biosimilars to achieve their potential for lowering the cost of cancer care in the United States.
Acknowledgments: This research was presented in part as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 22nd Annual Meeting in Boston, MA, May 2017.
Biosimilars are biological medicines that contain a highly similar version of the active substance of an already approved biologic, referred to as the “innovator” or “reference product.”1 Biosimilars have been proposed as one way to lower US health care costs by entering the market at a reduced price.2 To facilitate market entry of biosimilars, the Food and Drug Administration (FDA) has established abbreviated regulatory pathways leading to approval.3 Biosimilars must establish similar quality, safety, efficacy, and immunogenicity characteristics to the innovator, but minimal differences that are not clinically meaningful are permitted.4 Once similarities are established, the FDA allows at least one of the innovator indications to be listed as an indication to the biosimilar.4 In addition, the FDA allows extrapolation of safety and efficacy data from one biosimilar indication to another after rigorous requirements are fulfilled.5 Regulatory guidelines are designed to assure that biosimilars are safe and effective when used in place of innovators regardless of disease type and stage.6
Until recently, only the biosimilar to filgrastim was approved for use in cancer patients.4 As patents of more biologics expire in the next few years, more biosimilars are expected to enter the US market.2 In fact, biosimilars to bevacizumab (bevacizumab-awwb; Mvasi) and trastuzumab (trastuzumab-dkst; Ogivri) were recently approved by the FDA, and rituximab biosimilars are expected to follow.4 With more biosimilars in queue to get FDA approval, understanding oncology providers’ perceptions of biosimilars’ efficacy, toxicity, and relative cost to value is essential to drive strategies for market uptake.
Physicians’ acceptance and understanding of biosimilars have been questioned. Cohen et al surveyed 1201 physicians of various specialties (ie, dermatology, gastroenterology, hematology/oncology, nephrology, and rheumatology) who were heavy prescribers of biologics.7 The results highlighted a significant need for evidence-based education about biosimilars with a specific focus on regulatory processes, safety, immunogenicity, and extrapolation.
We aimed to better understand community oncologists’ general biosimilars understanding and perception of barriers to biosimilars acceptance. We did so by conducting surveys of physicians during live meetings that focused on the topic. The aim was to identify challenges that might hinder community oncologists’ use of biosimilars in oncology in order to determine appropriate responses to address these challenges. The future success of biosimilars in the US oncology market will heavily depend on oncologists’ acceptance of these agents and on payers considering biosimilars as the preferred medicines when possible.
Methods
Between November 2015 and November 2017, a total of 510 US-based community oncologists/hematologists and practice administrators were surveyed during 8 live regional conference meetings to assess their knowledge of biosimilars and perceived barriers to their adoption.
Participants were chosen from meeting attendee lists. The practice administrators who were selected to participate in this study were those who were primarily involved in purchasing biologics and/or biosimilars for their respective practices and were representative of the prescribing patterns and acceptance of their own physicians about biosimilars.
The 25-question survey was created de-novo by the authors and included questions on respondent demographics, type of practice, practice location, and detailed questions related to biosimilars. The survey included multiple choice answers to specific questions when necessary. Audience response system devices were used to capture participants’ responses and allowed more than one answer selection when appropriate. The accompanying data tables in this article represent a selection of 13 of the 25 survey questions that had the highest number of responses; tables are separated based on 3 distinct aspects of biosimilars.
During survey administration at these live meetings, follow-up discussions sometimes took place after answers for some questions were submitted. These discussions were not easy to capture; pre- and post-discussion questions and answers were not used. The answers as presented in this research report are what was generated from this market research study.
Results
The numbers and percentages cited below are the collective data (N = 510) for all respondents from the 8 live meetings. It should be noted, though, that not all questions were asked in each of the meetings, and not every respondent answered all questions, therefore, there was a variability in the number of respondents for each question.
Respondents represented a variety of practice types: large size (> 10 physicians: 20%), medium size (6-10 physicians: 15%), small size (2-5 physicians: 17%), solo practice (15%), hospital-owned community practices (16%), community-based hospitals (5%), and university-owned hospitals (11%). Participants represented all geographic areas in the United States: (38% South, 26% Midwest, 17% Northeast, and 19% West).
When asked about their general familiarity with biosimilars, 79% physicians (239 of 302 respondents) stated they are very or somewhat familiar. Almost all physicians (92%; 58 of 63 respondents) said they are aware of the 3 currently approved biosimilars with oncologic indications, and 65% of the physicians (126 of 196 respondents) stated they had prescribed a biosimilar at some point in the preceding 12 months. Also, 62% (24 of 39 respondents) suggested that they are aware of 2 to 4 biosimilars that are currently under development, although this perception was not necessarily supported with cited data.
Almost 95% of surveyed physicians (38 of 40 respondents) were very or somewhat confident that biosimilars are as safe and effective as their reference biologics. This level of confidence translated into how oncologists plan on prescribing currently available biosimilars, soon-to-be-available biosimilars, and biosimilars that are likely to be approved in various disease settings (Table 1). Most oncologists felt that prescribing biosimilars is suitable whether the goal is cure or disease control.
Regarding the regulatory aspects of approving biosimilars, 22% (13 of 57 respondents) were not familiar with how biosimilars get approved, and almost 49% (28 of 57 respondents) did not fully understand or endorse the concept of extrapolation. Also, 81% (29 of 36 respondents) expressed their hesitancy and reluctance to prescribe a biosimilar until an average sales price (ASP) of a biosimilar is established. Once an ASP is available, 77% (30 of 39 respondents) expressed comfort with prescribing a biosimilar. Other regulatory aspects are summarized in Table 2.
Cost and reimbursement challenges are obvious concerns to community oncologists, but 90% (54 of 60 respondents) agreed that lower prices of biosimilars do not imply lesser efficacy. Interestingly, over half of surveyed oncologists (30 of 58 respondents) believed that more than 60% of commercial or government payers will mandate the use of biosimilars, if available. Other cost and reimbursement concerns are summarized in Table 3.
Most community oncologists (77%; 40 of 52 respondents) were receptive to receiving additional educational information regarding biosimilars, and 79% of those (41 of 52 respondents) advised that communications from professional organizations, such as the American Society of Clinical Oncology (ASCO), are their preferred learning channel. A reliable reputation, ability to generate clinical trial data, and having a business acumen about community oncology needs and challenges are the top 3 attributes cited by respondents that would elevate their acceptance of the biosimilar manufacturer.
Discussion
This survey of 510 oncologists in the United States shows that physician concerns about regulatory pathways exist and that, once biosimilars are approved, the disease stage and goal of therapy are not a major factor in the prescriber decision-making. There is an opportunity to educate oncologists about FDA regulatory processes, as almost one quarter of respondents were uncomfortable about the process as is. Although physician awareness and favorable perceptions of new market entrants do not guarantee their adoption, they are likely a critical first step to drug utilization.
When regulatory guidelines were explained during follow-up conversations at the live meeting conferences, the majority of respondents expressed a reasonable level of comfort with FDA regulations to approve biosimilars. In addition, less than 20% of these surveyed physicians continued to express concerns about biosimilar regulatory pathways, which essentially centered around substitution at the pharmacy level (Table 2). Also, most oncologists suggested that practice guidelines are needed to aid in the decision-making process on when to prescribe a biosimilar as opposed to the reference product. The ASCO and National Comprehensive Cancer Network (NCCN) guidelines currently incorporate biosimilars into their pathways.8 In fact, the NCCN considers the use of any filgrastim biosimilar as category 1 in febrile neutropenia guidelines.9 This implies that using filgrastim, tbo-filgrastim, or filgrastim-sndz is acceptable by the NCCN, leaving the decision to individual prescribers. Better visibility and more educational platforms that highlight these guidelines are needed to disseminate the information effectively to community oncologists.
Since filgrastim-biosimilar has been the only approved biosimilar in the United States until recently, and as filgrastim-biosimilar is used for supportive care as opposed to active anticancer therapy, we sought to understand whether the active disease state (metastatic vs early stage) affects oncologists’ decision on biosimilar prescribing. When we asked questions about rituximab biosimilar, the majority appeared comfortable prescribing either for palliative use or when cure is the goal (Table 1). This is reassuring, as this biosimilar could be available in the next 12 to 18 months.
Biosimilars are theorized to lower health care costs by having lower prices than their counterpart biologics. Not surprisingly, oncologists expect significant discounts ranging from 11% to >30%; these discounts appear to be a motivator for oncologists to recommend a biosimilar. As profit margins for oncology practices shrink, cost and expenses to practices are a factor in prescribing decisions. It is important to educate providers on how reimbursement is assured when prescribing biosimilars. Out-of-pocket costs are also a factor that might shift prescribing toward a biosimilar vs a reference biologic. There appears to be a hesitancy to prescribe a biosimilar before an ASP is established—an issue that policymakers need to be aware of and address efficiently.
Extrapolation of market uptake of biosimilars based on the history and experience with generic nonbiologic oncolytics may be problematic and is certainly a false equivalency. Generics enter the market as exact replicas of the brand, chemically identical, and thereby are deemed interchangeable by the FDA. Biosimilars enter the market in a very different light. Their complex biosynthesis prevents them from achieving exact chemical replication as is the case with the reference brand biologics with which they will compete. The result of this inherent variation requires a very different regulatory process and thereby the need to conduct randomized controlled clinical trials (RCT) as part of the FDA approval process, albeit for a single labeled indication. Labeled indications beyond those studied in RCT may be granted by the FDA based on extrapolation. Such differences in research and development costs should allow market entry at a lower price than the reference brand, but the difference, thus far, is in the 10% to 20% range vastly different than the +90% price differentials seen when generic oncolytics enter the market. In short, biosimilars enter the market with limited noninferiority design RCTs, labeled indications mostly by extrapolation, and narrow price differentials. The increasingly favorable perceptions of providers are a critical first step to their adoption, but continued market research is needed to understand how such perceptions overcome formidable barriers to robust adoption and use.
There is little doubt that biosimilars are here to stay and that more biosimilars will continue to enter the US oncology market. Whether biosimilars will eventually lead to a lower total cost of cancer care is unknown and requires longer term follow up.10 Lower costs of biosimilars is a critical component for market uptake. Moreover, assuring that society guidelines embrace the use of biosimilars will increase the likelihood of commercial success.
There were some limitations to the study. As mentioned above, some survey questions were not answered by all surveyed physicians, thus there was some variability in the number of responding physicians per questions posed. This limits some of the interpretation of findings; nonetheless, the study provides potential trends and a window into the thought processes of oncologists regarding biosimilars, as is the purpose of primary market research. Subsequent longitudinal studies are needed to assess whether perceptions regarding biosimilars changes over time. In addition, discussion of cost implications is rather complex and outside the scope of the present article; a subsequent article is needed to adequately discuss the economic implications of biosimilars.
Conclusion
This study provides an overview of how physicians perceive new market entrants and regulatory pathways for biosimilars, outlining areas for improvement. More educational platforms to highlight guideline recommendations related to biosimilars is also needed. Overcoming barriers to acceptance may lead to increased utilization of biosimilars and lower health care costs.
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