Evolving Policy Issues in Oncology: Revisiting Biosimilars and Molecular Testing

Author: Jessica DeMartino PhD
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In April 2013, NCCN held the NCCN Oncology Policy Summit, “Evolving Policy Issues in Oncology—Revisiting Biosimilars and Molecular Testing” in Washington, DC. Stakeholders gathered to examine how biosimilars and molecular testing in oncology, topics addressed in 2011 NCCN Policy Summits, have changed. The program, moderated by Clifford Goodman, PhD, of The Lewin Group, consisted of 2 short presentations and 2 roundtables with vigorous discussion and audience participation.


The morning session started with an overview of the milestones of biosimilar development from James Hoffman, PharmD, MS, BCPS, Medication Outcomes & Safety Officer at St. Jude Children’s Research Hospital. One major milestone was the Patient Protection and Affordable Care Act, signed in 2010, which contains a subtitle, “The Biologics Price Competition and Innovation Act of 2009.” The Act establishes an abbreviated approval pathway for biological products shown to be “highly similar” (biosimilar) to, or “interchangeable” with, an FDA-licensed biological product.1 In February 2012, the FDA released its draft guidance on the development of biosimilars in the form of 3 separate guidance documents, “Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product,” “Scientific Considerations in Demonstrating Similarity to a Reference Product,” and “Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.” The introduction of biosimilars in the United States is of great interest to many different stakeholders as they have the potential to impact the cost of innovator biologics. These agents accounted for 55% of cancer drug expenditures in 2011, totaling $157 billion.2

Dr. Hoffman reviewed key consensus statements, recommendations, and challenges identified by the NCCN Biosimilars Work Group in 2011 and highlighted areas of concern still surrounding biosimilars—safety, tracking, naming, substitution practices, and provider education. Dr. Hoffman also touched on the role of state pharmacy boards and pending state laws regarding substitution of biosimilars. When most stakeholders were first considering biosimilars, they were thinking about the federal level and what legislation and guidance federal organizations would provide. Now the issue is coming to the state level. State legislatures are specifically looking at the pharmacist’s role in dispensing a biosimilar product and what communication should occur to a patient, the prescribing physician, and other stakeholders.

The introductory presentation was followed by a roundtable discussion moderated by Dr. Goodman and including panelists Jeff Allen, PhD, of Friends of Cancer Research; Stan Bukofzer, MB, BCh, MMed, from Hospira; Leah Christl, PhD, with the FDA; Dr. Hoffman; Richard Markus, MD, PhD, from Amgen; Lee Newcomer, MD, MHA, from UnitedHealthcare; Marjorie Shapiro, PhD, from the FDA; and Andrew Zelenetz, MD, PhD, from Memorial Sloan-Kettering Cancer Center.

With patients potentially exposed to the same drug multiple times over a lifetime, the topics of interchangeability and substitution were discussed in great depth. No FDA guidance is currently available on interchangeability, but the FDA is working on developing some, according to Dr. Christl. Dr. Bukofzer commented that safety concerns around switching between biosimilars and innovator drugs should hold for switching between all biologics, as there is inherent variability both in lots of an innovator drug and in different innovator drugs that are used to treat the same indication.

Although interchangeability is important, the FDA is currently focused on the demonstration of biosimilarity, encouraging sponsors to submit early with significant analytical data packages to support biosimilarity. It was suggested that the stronger the analytical studies the less need there will be for clinical studies, with the exception of pharmacokinetic (PK) and pharmacodynamic (PD) studies. This may seem counterintuitive to physicians who may want clinical studies before using biosimilars. The panel suggested that PK/PD data will be needed for each indication where a drug may be used because of differences in diseases and how drugs are metabolized in each disease state.

An audience question brought up biosimilar efficacy and how physicians can be sure of efficacy if only limited efficacy data are needed for FDA approval. Dr. Shapiro explained the obstacles biosimilar manufacturers have surpassed to get to the point of clinical use. Stakeholders will need to trust the analytical data supplied to the FDA and the ability of the FDA to evaluate data packages. Monitoring effectiveness and tracking adverse events were also discussed. Panelists noted that effectiveness data and adverse events can be tracked through claims data and other sources once a biosimilar has been approved. Dr. Markus explained that Amgen has a large safety group that routinely surveys claims databases to look for data on their own products.

The panel discussed uptake and costs of biosimilars. The panelists noted that safety, including immunogenicity, will be the first consideration, followed by cost. Dr. Hoffman suggested that some biosimilars, like growth hormones, will likely be accepted and used sooner because of their “simpler” nature and use in non-life-threatening situations. The panelists also agreed that because the large majority of early biosimilars will primarily be used in hospitals, the update should be quicker than if they were distributed to patients at the local pharmacy level.

Dr. Newcomer noted that payers would welcome any intervention that lowers costs, including biosimilars. Payers can encourage the uptake of biosimilars by only reimbursing for the lower priced biosimilar or reimbursing at the same rate as the innovator, despite its lower acquisition cost. The panelists debated the importance of a biosimilar being labeled “interchangeable” to see price competition and cost savings. Dr. Markus suggested that true price competition will come with having several high-quality biosimilars to choose from that may or may not be deemed interchangeable.

The question of how many competitors are needed to see real cost savings went unanswered. Dr. Zelenetz suggested that interchangeability is the best and simplest way to get cost savings because pharmacists are involved and they care about cost. Dr. Zelenetz was referring to the use of P&T Committees in hospitals and health systems that determine formularies and therapeutic interchange. If a P&T Committee decides a biosimilar is therapeutically equivalent, all prescriptions for the drug will be filled with the biosimilar. Dr. Newcomer suggested that if the FDA deems a biosimilar interchangeable, P&T Committees will make the switch on their formularies automatically, without much debate. P&T Committees have strong influence at the organizational level. In private practice, physicians are not governed by P&T Committees and will need to make their own decisions to use biosimilars. Thus, biosimilar uptake may be slower in the private practice setting, but specialty pharmacies have the ability to encourage and require the use of biosimilars outside hospitals.

The panelists also agreed that biosimilars will be used off-label, as most cancer drugs are, and their use will be extrapolated across the indications that the originator is used for. Dr. Bukofzer stressed the importance of pharmacovigilance surveillance systems that can adequately pick up any issues in extrapolated or off-label uses as soon as possible. The FDA has not decided at this point how biosimilars will be labeled to indicate biosimilarity and interchangeability, but the European model is to include this information on the label.

The roundtable concluded with panelists agreeing that clinical and practical experience, technologic advances for characterizing biologics, education of providers and patients, and big data that support use and show any adverse events will be the factors that encourage the uptake of biosimilars and ultimately bring them to stakeholders.

Molecular Testing

As interest in personalized medicine continues to increase, so does interest in the development of molecular tests, especially in the development of laboratory developed tests (LDTs) and companion diagnostics, and the related search for clinically meaningful molecular biomarkers. Mark Kris, MD, Chief, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, started the afternoon session by explaining how the advent of molecular testing has changed the treatment of lung cancer. He highlighted the important role pathologists play in molecular testing as legal and moral guardians of tissue samples. He suggested that pathologists should lead the advancement of molecular testing while being supported by other physicians. Dr. Kris concluded with predictions that in 10 years more validated targets with available biomarkers and therapies and comprehensive, cheaper, and faster multiplex testing for all targets at diagnosis will be available.

Pam Germain, MBA, from Roswell Park Cancer Institute; Ellie Guardino, MD, PhD, from Genentech; Lawrence Jennings, MD, PhD, from the College of American Pathologists; Dr. Kris; Elizabeth Mansfield, PhD, from the FDA; Doug Moeller, MD, from McKesson Health Solutions; and Dr. Newcomer participated in a follow-up roundtable discussion. The group discussed the challenges for the broader integration of molecular testing into oncology practice, development of LDTs, companion diagnostics, and coding and reimbursement of molecular testing.

Dr. Guardino discussed the upside of molecular testing for patients: they may receive more efficacious treatments and have a better quality of life. Appropriate use of molecular testing can also make care more cost-effective for both patients and payers. Despite the advent of technology and molecular tests, a learning curve still exists, and education is needed. Physicians must understand what tests are available, when they should be used, who should receive the tests, how to interpret results, and the value, both clinically and financially, of the tests.

Technologic advances have reduced the cost of sequencing the entire genome, according to Dr. Moeller. However, although the cost per test is decreasing, the number of tests run is increasing. Thus, lots of mutations can be tracked, but pathologists and clinicians often do not know the clinical significance, if any, of the mutation. Panelists suggested that it is best to collect the information now and then retrospectively examine outcomes and mutations to find correlations. The group also discussed that not all mutations are created “equal”. Some may be pathogenic while others on the same gene are benign.

Dr. Moeller explained that the complexity is not so much in the actual testing, but in the interpretation and reporting of results. Dr. Jennings expressed confidence in the laboratories conducting the testing as they are accredited and monitored through proficiency testing and laboratory inspections. Criteria for clinical laboratories include qualification of instruments, qualification of reagents, validation, and monitoring. The group discussed the merits of the Clinical Laboratory Improvement Amendments (CLIA) and their effect on molecular testing. Dr. Mansfield stated that CLIA is really a minimum standard that measures the quality of laboratory operations, not an overarching regulatory scheme. Several panelists agreed that CLIA was not meant to handle the complexity of testing seen today. An additional complicating factor in molecular therapy is the inherent heterogeneity in tumor samples, which can lead to incorrect typing of a tumor. This is an area that needs continuous consideration and improvement.

In the discussion of coverage, reimbursement, and billing, Dr. Newcomer explained that he is looking for analytic and clinical validity and clinical utility when considering whether to cover and reimburse for a molecular test. He said they will consider a molecular test in the same way as a new drug. Dr. Newcomer also expressed frustration over the coding system for molecular tests and shared an example. In his example there was a genome with 300 elements, but only 4 had evidence supporting use. Dr. Newcomer pointed out they will only pay for the 4 proven elements and would need to figure out a fair price considering the cost-effectiveness of running the tests at the same time and the decreasing price of technology.

Ms. Germain explained that the stacked coding system is being phased out as CMS and the AMA are introducing single CPT codes for molecular diagnostic tests. The idea is that a payer will actually know what test they are being billed for. However, Dr. Newcomer suggested that the new system may still not be adequate. He explained that while a test for KRAS may have one code in this new system, there may still be 1000 different kinds of KRAS tests. This large variation in methodology of tests also equates to a large variation in the cost of each test, and the payer is still unsure of how much to pay. To help determine appropriate reimbursement, Medicare asked for input from cancer centers, but as of January 13, 2013, CMS was not ready to publish a fee schedule. CMS left it up to local contractors to come up with a fee schedule around the country. Two contractors have developed fee schedules, one based on gap-filling methodology and the other on cross-walking, but neither model was endorsed by panelists.

The audience questioned what private payers will do with the prices Medicare has set. Dr. Newcomer explained that, as a temporary fix, UnitedHealthcare based their reimbursement on the predominant regional contracts, but they would like to use Z-code identifiers and negotiate a price for each specific test. Another audience concern was that current pricing is not transparent. Dr. Jennings shared that the College of American Pathologists submitted what they believed to be reasonable pricing to CMS but were largely ignored. The panelists agreed that a rationale, transparent, and fair reimbursement system for molecular testing is still needed.

The roundtable concluded with panelists sharing thoughts on the factors that will bring molecular testing to the mainstream of oncology: greater collaboration across stakeholder groups, greater amounts of clinical information and improved access to this information, a rational reimbursement strategy, greater knowledge transfer, appropriate infrastructure, and improved understanding of the biology of all kinds of cancer care.


  • 1.

    Federal Register, Volume 75, No. 192, Tuesday, October 5, 2010, page 61497.

  • 2.

    Doloresco F, Fominaya C, Schumock GT et al. . Projecting future drug expenditures: 2011. Am J Health Syst Pharm 2011;68:921932.

Jessica DeMartino, PhD, is Manager, Health Policy Programs, at NCCN. She joined NCCN in 2008 as a Policy Fellow initially focused on understanding payers’ use of NCCN Guidelines and Drugs and Biologics Compendium. Dr. DeMartino is responsible for developing and executing the NCCN Oncology Policy Summit series and resulting white papers along with the NCCN Patient Advocacy Summit. She is also responsible for any policy issues that arise at NCCN. Dr. DeMartino earned a doctorate in organic chemistry from The Scripps Research Institute and a Bachelor of Science degree in biochemistry from the University of Delaware.

The ideas and viewpoints expressed in this commentary are those of the author and do not necessarily represent any policy, position, or program of NCCN.

  • 1.

    Federal Register, Volume 75, No. 192, Tuesday, October 5, 2010, page 61497.

  • 2.

    Doloresco F, Fominaya C, Schumock GT et al. . Projecting future drug expenditures: 2011. Am J Health Syst Pharm 2011;68:921932.

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