A Strategic Review of Biosimilars in Oncology Practice
Philip Schwieterman, PharmD MHA
Director of Oncology and Infusion Pharmacy
The introduction of biosimilars into the U.S. healthcare system has been met with mixed responses from key players, including healthcare providers, drug manufacturers, specialty and infusion pharmacies, health benefit providers (payers), and policy makers. Although these medications bring hope for minimizing cost and improving patient access to expensive medications, their presence has disrupted many channels in the specialty pharmacy market connected to drug pricing, formulary coverage, reimbursement, and clinical utilization. Many oncology pharmacists have become comfortable with the concept of biosimilars following the 2015 release of the first biosimilar agent in the United States, filgrastim-sndz (Zarxio), and a handful of other nononcology biosimilars. Two U.S. Food and Drug Administration (FDA) approvals in 2017, for bevacizumab-awwb (Mvasi) and trastuzumab-dkst (Ogivri), have brought increased attention to the use of biosimilars in the cancer setting because these agents are the first approved biosimilars for many biologics approved for the treatment of cancer.
According to the FDA, a biosimilar is a biological product that is highly similar to and has no clinically meaningful difference from an existing FDA-approved reference product.1 The pathway for approval of biosimilar agents in the United States was established in 2009 by the Biologics Price Competition and Innovation Act (BPCIA), which updated section 351(k) of the Public Health Service Act of 1944. This update provided succinct details on how to bring biosimilars to market, including requirements for licensing, testing, manufacturing, safety, exclusivity, labeling, the definition of biosimilars versus interchangeable products, and required interactions with the manufacturer of the reference product. The BPCIA was eventually enacted as part of the 2010 Patient Protection and Affordable Care Act, and since that time, payers, manufacturers, and healthcare providers have been preparing for the release of biosimilar agents.
The FDA’s Center for Drug Evaluation and Research maintains a list of all FDA-approved biologics. This online database, called the Purple Book, includes the medication names, respective dates of licensure, patent expiration dates, and other types of information for all biologics and biosimilars. To date, nine biosimilars have been approved by the FDA through the BPCIA pathway for six biologics, but only three are currently available for distribution and sale (see Table 1 - see PDF).2,3
The approval, manufacturing, and sale of many biosimilar products, including both bevacizumab-awwb and trastuzumab-dkst, have been held up in complicated lawsuits secondary to varying interpretations of patent law, as well as interpretations of the BPCIA as it relates to the type of communication that must occur between the manufacturer of the biosimilar product and the manufacturer of the reference product.
In November 2016, Amgen officially announced its intention to produce and market a biosimilar to bevacizumab (Avastin), which ultimately gained FDA approval 10 months later.4 However, since November 2016, Genentech, the manufacturer of bevacizumab (Avastin), has filed multiple litigious complaints and patent infringement suits about varying interpretations of the BPCIA, which has slowed both the approval and market availability of the biosimilar.
Genentech and Roche, who manufacture and market trastuzumab (Herceptin), took a different approach when Mylan and Biocon communicated their interest in developing a trastuzumab biosimilar. In this case, the companies signed a collaborative global licensing agreement in March 2017 that was designed to “provide a clear pathway for Mylan to commercialize its trastuzumab product in various markets around the world.”5 Although details of the agreement remain confidential, it is obvious that Mylan and Biocon were committed to overcoming patent considerations early in the process, which paves the road for manufacturing and distributing their biosimilar, set for 2019.6
The litigation or “patent dance” observed with bevacizumab-awwb has been seen with the release of most other biosimilar products and may lead to months or years of delay for each product. Despite these delays, the ongoing approvals of these products will only increase, which means that oncology pharmacists should prepare for their utilization with the clinical, financial, and regulatory aspects in mind.
For pharmacist clinicians, a primary interest concerning the use of biosimilars is their clinical effectiveness and safety profiles compared with the reference product. Currently no interchangeable biologics are on the market that, according to the BPCIA, would allow the product to “be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”7 However, developers of the current noninterchangeable biosimilars must meet or present strict clinical, safety, purity, potency, analytical, and nonimmunogenicity data and manufacturing data to prove that the biosimilars are equivalent to the reference product. Critics of biosimilars are quick to point out that the clinical data required for approval through the BPCIA are limited to just “one or more appropriate conditions of use for which the reference product is licensed,” meaning that the biosimilar may gain an FDA label for the full spectrum of indications for the reference product through the study of use in only one disease state.7 Fortunately, the FDA’s review process, coupled with biosimilar utilization in Europe and initial data in the United States, supports the view that these products have similar profiles to the reference product.
Another major implication of biosimilar use is the potential impact on drug cost and increased access for patients. A recent market study performed by the RAND Corporation estimated that the implementation of biosimilars would save the U.S. healthcare system $54 billion over the next decade, with a potential minimum and maximum savings of $25 billion and $150 billion, respectively.8 Although this perspective proactively identifies the large potential swing of cost savings, even the conservative number is enough to cause excitement, especially because the roughly 3% of patients receiving specialty medications in the United States now account for more than 40% of total drug spending.9 The cost savings associated with biosimilar implementation is secondary to the lower cost of the biosimilar products because less overhead is needed for research and development, and the costs of the reference products will remain lower as their manufacturers attempt to stay competitive in the market. In an ideal world, these lower costs would spur “top-down economics”: pharmacies and clinics would purchase the medications for less, health insurance companies would see less spent per member, and patients would subsequently pay lower premiums and copays for their subspecialty care.
Although lowering overall healthcare costs is an important sociological endeavor, it is also important for dispensing pharmacies to understand the revenue cycle as it relates to the cost and reimbursement for both reference biologics and biosimilars to ensure their fiscal viability. Most of the biologics in the oncology setting that are nearing patent expiration and subsequently will become eligible for biosimilar competition are administered via the intravenous route by a healthcare professional. A recent poll of health insurers showed that 72% of payers cover intravenous oncology products solely under the medical benefit.10 Because of complexities associated with revenue cycle billing through the medical benefit, infusion pharmacies will be at risk for dispensing a nonpreferred or uncovered product, which may lead to lack of payment for services rendered. Scenarios in which infusion pharmacies might not get paid through the medical benefit include these:10
The reference product was dispensed when the payer’s preferred formulary agent was a biosimilar.The biosimilar product was dispensed when the payer’s preferred formulary agent was a reference product or another biosimilar.
Biological parity exists (i.e., the use of biologics aligns with the payer’s medical necessity policies), but an authorization was not obtained for any product.
Authorization for one product was obtained, but another product was dispensed.
The medication was approved through the prescription insurance but billed through the medical insurance.
The patient recently lost or changed insurance coverage.Accordingly, it remains crucial for oncology infusion pharmacies to maintain a strong and proactive financial support team to ensure that the biologic medications prescribed and dispensed align with the formulary for each specific health benefit payer. Many payers, such as Medicare, will cover all forms of the biologics as long as biological parity exists. In this case, it is important to review both the purchasing costs of the reference and biosimilar products and their respective reimbursement amount. Though one product may be less expensive, the reimbursement amount may also be significantly less, meaning a smaller margin per each dispensing. Medicare has attempted to favorably adjust its reimbursement for biosimilars through Part B to incentivize their utilization.11 However, Part B reimbursement methodologies have been scrutinized or changed without much consistency in recent years, so it is important to stay updated on current standards in this setting.
The management of biosimilars in an institution should also be driven by other factors. It is important to note that the reimbursement process for biosimilars within hospitals will likely vary greatly between the inpatient setting and the outpatient infusion setting. For that reason it is important to understand the revenue cycle in both areas across all payers when one is strategically assessing biologic and biosimilar utilization. Also, state laws may require that reference products or biosimilars be dispensed in certain instances. The Academy of Managed Care Pharmacy supports the Biosimilar Resource Center, “an unbiased, policy-neutral repository of educational resources and information on biosimilars” that provides links to each state’s specific regulations.12,13 Finally, the FDA makes available an abundance of information that will also aid in the assessment and implementation of biosimilars.14
Several biologics, including rituximab, cetuximab, eculizumab, and pegfilgrastim, will be nearing the end of their patent life in the coming years, making them eligible for biosimilar competition.15 Although the rollout of these products into the market has been slow, their arrival is inevitable. It is therefore important for pharmacists to assess the value of these medications from a clinical and financial standpoint, considering both their own practice and the overall U.S. healthcare system.
- U.S. Food and Drug Administration. Biosimilar and Interchangeable Products. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580419.htm#biosimilar. Accessed November 30, 2017.
- U.S. Food and Drug Administration. Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm411418.htm. Accessed December 17, 2017.
- U.S. Food and Drug Administration. Biosimilar Product Information. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm580432.htm. Accessed December 17, 2017.
- U.S. Food and Drug Administration. FDA approves first biosimilar for the treatment of cancer. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm576112.htm. Accessed November 30, 2017.
- Mylan Pharmaceuticals. Mylan Announces Global Settlement and License Agreements with Genentech and Roche on Herceptin®. http://newsroom.mylan.com/2017-03-13-Mylan-Announces-Global-Settlement-and-License-Agreements-with-Genentech-and-Roche-on-Herceptin-R. Accessed November 30, 2017.
- Mylan Pharmaceuticals. U.S. FDA Approves Mylan and Biocon’s OgivriTM, the First Biosimilar for Trastuzumab, for the Treatment of HER2-Positive Breast and Gastric Cancers. http://newsroom.mylan.com/2017-12-01-U-S-FDA-Approves-Mylan-and-Biocons-Ogivri-TM-the-First-Biosimilar-for-Trastuzumab-for-the-Treatment-of-HER2-Positive-Breast-and-Gastric-Cancers. Accessed November 30, 2017.
- U.S. Food and Drug Administration. H.R.3590 Patient Protection and Affordable Care Act. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ucm216146.pdf. Accessed November 30, 2017.
- Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. Santa Monica, CA: RAND Corporation, 2017. https://www.rand.org/pubs/perspectives/PE264.html. Accessed November 30, 2017.
- IQVIA Institute. Medicines Use and Spending in the U.S.: A Review of 2016 and Outlook to 2021. May 4, 2017 report. https://www.iqvia.com/institute/reports/medicines-use-and-spending-in-the-us-a-review-of-2016. Accessed November 30, 2017.
- EMD Serono Specialty Digest, 13th ed., 2017. https://specialtydigestemdserono.com/. Accessed November 30, 2017.
- Centers for Medicare and Medicaid Services. Final Policy, Payment, and Quality Provisions in the Medicare Physician Fee Schedule for Calendar Year 2018. https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2017-Fact-Sheet-items/2017-11-02.html. Accessed November 30, 2017.
- Academy of Managed Care Pharmacy. AMCP Launches Online Biosimilars Resource Center for Pharmacists, Physicians, Other Providers. http://www.amcp.org/Newsletter.aspx?id=21194. Accessed November 30, 2017.
- Biosimilar Resource Center. https://www.biosimilarsresourcecenter.org. Accessed November 30, 2017
- U.S. Food and Drug Administration. Biosimilars. https://www.fda.gov/ drugs/developmentapprovalprocess/howdrugsaredeveloped andapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/default.htm. Accessed November 30, 2017.
- U.S. Food and Drug Administration. Center for Drug Evaluation and Research List of Licensed Biological Products with (1) Reference Product Exclusivity and (2) Biosimilarity or Interchangeability Evaluations to Date. https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM560162.pdf. Accessed November 30, 2017.