Senior Lead, Healthcare Quality and Policy
Hutchinson Institute for Cancer Outcomes Research
Fred Hutchinson Cancer Research Center
Professor of Medicine
University of Washington School of Medicine
Gary H. Lyman, MD, MPH, FASCO, FACP, FRCP, has no real or apparent conflicts of interest to report.
Although biologic therapies for cancer can dramatically improve outcomes for many patients, their high costs have resulted in somewhat tempered excitement. As patents on these products expire, biosimilars—biologic agents that are highly similar but not identical to an approved reference biologic—have begun to emerge as treatment options, increasing competition and potentially reducing the cost of biologic cancer therapies. Here, I discuss why some of the key reasons biosimilars may be more affordable could also pose challenges to their widespread adoption.
Biosimilars May Help to Curb Rising Healthcare Costs of Cancer Therapy
With the median monthly cost of treatment with new biologic cancer therapies exceeding $10,000—an amount that is at least 2-fold greater than the median monthly household income in the United States—patients and their families face an increasing financial burden that may limit access to effective cancer therapies or even prevent adequate treatment of potentially curable cancers. As such, providers, professional organizations, and policymakers are looking at possible strategies for controlling these costs. Competitive development of biosimilars is likely to result in a reduction in drug pricing. In support of this strategy, ASCO recently published a statement on the important role of biosimilars as part of the complex solution to rising cancer care costs.
To achieve a decrease in price, the requirements for regulatory approval have been modified for proposed biosimilars, placing greater emphasis on molecular characterization and preclinical pharmacology and immunogenicity studies and less emphasis on the need to conduct multiple large phase III clinical trials. Biosimilarity, once demonstrated in a specific patient population, may be extrapolated to or extended across multiple indications of the reference biologic given sufficient scientific justification. Factors considered for this determination include mechanism of action, biodistribution, and expected toxicities.
The shift in these requirements has been made possible by nearly a decade of experience with biosimilars showing no evidence of loss of efficacy or new safety concerns. However, without the requirements for extensive clinical trial data, patients and providers alike may be wary of biosimilars as effective treatment options if not properly educated.
Further Education Is Needed to Enhance Adoption of Biosimilars Into Clinical Practice
Along with their statement that biosimilars may be cost-effective, ASCO also acknowledged that confusion or uncertainty could negatively affect biosimilar integration into clinical practice. They have consequently called for education of all stakeholders regarding biosimilars, their regulatory approval, and their appropriate use. With less reliance on clinical data, it is critical that providers are actively involved in postmarketing surveillance efforts. Indeed, with the recognized changes, or drift, of molecular characteristics and function that may occur during the complex manufacture of any biologic agent, including biosimilars, there is a need for continuous vigilance. This will help to generate data on maintenance of efficacy, the development of neutralizing antibodies, and any evidence of delayed or unusual toxicities not previously observed, helping providers to feel more confident in prescribing biosimilars.
Several other biosimilar-related topics may be new to providers and patients, all of which could impede adoption if not adequately understood. For instance, the novel naming convention of biosimilars attaches a meaningless, 4-letter suffix to the nonproprietary name of the agent. The concepts of switching, substitution, and interchangeability as they apply to reference biologics vs biosimilars must also be understood.
As of early December 2018, there are 15 approved biosimilars in the United States, including 5 supportive care agents used in oncology and 3 cancer therapies that will become available in practice in the coming year: bevacizumab-awwb, trastuzumab-dkst, and rituximab-abbs.
Supportive care biosimilars have already been integrated into professional guidelines and, subsequently, into routine clinical practice. Recent experience, however, demonstrates that FDA approval of a biosimilar is necessary but not necessarily sufficient for clinical integration, which requires public reporting of preclinical and clinical data, ideally in peer-reviewed scientific publications. With fully transparent reporting, careful regulatory evaluation, continued education, effective communication with patients, and postapproval vigilance, utilization of these and the many biosimilars to follow is expected to increase progressively in the United States, leading to greater price competition and patient access to these important and potentially curative therapeutic options for patients with cancer.
What do you think represents the biggest barrier to implementation of biosimilars as part of cancer therapy? Share your thoughts in the comments box or by participating in the polling question. Then, read another installment in this series of certified expert commentaries—this time from Rowena N. Schwartz, PharmD, BCOP, on how biosimilars differ from reference biologics and small-molecule compounds.