Biosimilars: Where Are They Now?

Although biosimilars may be years away from their US debut, now is the time for pharmacists to educate themselves on this new class of agents so that they will be prepared to provide support for their appropriate use.

Recently, Moody’s Investors Service published a new report on the subject of biosimilars. In their press release on, “Biosimilars: Parsing the Industry’s Pipelines,” Moody’s concluded that while many companies are working to expand the global market of biosimilars, such products are at least 3 years away from being marketed in the United States.¹ In its report, “The Global Use of Medicines: Outlook Through 2016,” the IMS Institute for Healthcare Informatics similarly concluded that biosimilar growth will remain modest for several years.² Therefore, it would appear that biosimilar development is substantially in the future.

However, in the last 18 months, more than a dozen states have entertained legislation that would govern such things as substitution, record retention, physician notification, and patient consent as it relates to the dispensing of biosimilars.³ Pharmaceutical companies such as Amgen have initiated wide-ranging educational campaigns regarding the unique aspects of biological manufacturing.⁴ Finally, the recent marketing of Teva’s tbo-filgrastim (Granix), a biosimilar in Europe but a separately licensed biologic in the United States, has further complicated clinicians’ understanding of this new product category.

Given this array of varying opinions about the timing and size of the biosimilars market, many physicians and pharmacists may be inclined to devote their attention to topics of more immediate concern. However, such an approach would be unwise. While the most commonly used biologics may still be several years away from competition, additional biosimilars for some of the less complex products may come to market sooner.⁵ Also, the competing voices of the brand-name product manufacturers and the generic product manufacturers are actively at work to define the narrative of biosimilars, which may or may not assist in promoting an accurate understanding of biologic manufacturing and regulation. Health care providers, particularly pharmacists, should invest the time now to educate themselves and their physician colleagues to ensure a sound understanding of biosimilars. Failure to do so could greatly limit the financial opportunity represented by this new class of agents.

We Do Not Have a Choice

The most recent projections regarding pharmaceutical expenditures suggest that after a sustained period of insignificant or even negative growth, drug costs are anticipated to rebound in part due to the fewer number of generic opportunities that will exist over the next several years.⁶ In addition, the positions of prominence once held by small molecule medications, those for which generic competition is possible, are now occupied by biologic drugs such as adalimumab, infliximab, rituximab, and pegfilgrastim.⁶

This pattern holds regardless of the site of care, acute or non-acute.⁶ In the absence of substantial consideration and use of biosimilars, it will be very difficult to exert control over these expenses, particularly as many new agents, both small molecule medications and biologics, continue to come to market with total annual treatment costs in excess of $50,000.⁷ The recent notoriety given to sofosbuvir and its $1000 per dose price tag highlights the trends associated with the cost of new molecular entities.⁸ Whether the first true biosimilar is approved next month or in 5 years, health care practitioners must be ready from day one to evaluate their potential for appropriate use.

This Is Going to Take a Lot of Education: Why Not Start Now?

A 2011 survey of 277 clinicians conducted by the National Comprehensive Cancer Network documented the fact that the majority of responding pharmacists, physicians, and nurses were not at all familiar or were only slightly familiar with recent developments pertaining to biosimilars.⁹ It is highly unlikely that most direct practitioners fully appreciate the unique aspects of biologics, including the inherent variability seen in the manufacture of all recombinant-derived products and the potential for both originator molecules and biosimilars to cause unwanted immune responses.⁵ Understanding these differences along with the unique regulatory pathways for originator biologics and biosimilars will require a significant degree of attention and focus. In addition, adoption of biosimilars will necessitate a change in the way in which pharmacists and physicians conduct formulary evaluations.

The purpose of the biosimilar pathway is not to replicate the totality of clinical trial information associated with the originator product.⁵ The biosimilar pathway is built on a foundation of structural and functional characterization of the competing molecule.⁵ As a result, the clinical data required for approval are intended only to address any residual uncertainty to ensure a similar level of safety, purity, and potency as compared with the reference product.⁵ Clinicians will have to develop a level of comfort adopting biosimilars with this more focused amount of clinical data.

Although technically not a biosimilar in the United States, tbo-filgrastim can serve as a representative example of what we may expect with subsequently licensed biosimilar products. Tbo-filgrastim was approved by the FDA with phase III trial data from just under 700 patients.^10-12 Given the complexity and acuity of the disease states for which many biologics are used, some physicians and pharmacists may be hesitant to add such products to formulary without numerous clinical trials. Health care practitioners will need to understand and appreciate the validity of structural and functional analyses in demonstrating comparability of a biosimilar with a reference product.

Let’s Not Repeat Europe’s Mistakes

The European market frequently is cited as an indicator of what could transpire in the United States as biosimilars are introduced. Europe has had biosimilars approved since 2006, and in 2013 granted marketing authorization for its first biosimilar monoclonal antibody.⁵ However, uptake of biosimilars across the countries in Europe has been relatively modest. Recently, the Biosimilar Medicinal Products Working Party of the European Medicines Agency published a paper that addresses the most common concerns that appear to have limited the use of biosimilars in Europe.¹³ The authors conclude that “A clear understanding of the scientific principles of the biosimilar concept and access to unbiased information on licensed biosimilars are important for physicians to make informed and appropriate treatment choices for patients.”¹³ Therefore, successful adoption of biosimilars will be directly tied to the extent and availability of adequate education for clinicians, particularly prescribers.

Hope on the Horizon?

Given the long time we have waited for biosimilars, it is easy to see why clinicians might be discouraged. The biosimilar pathway took approximately a decade to receive congressional approval and finally was signed into law in 2010. It took an additional 2 years for the FDA to publish guidance information, which while helpful, did not address 2 of the most important points related to biosimilars—naming and interchangeability.⁵ It has been 2 years since those guidance documents were published and key aspects of biosimilar approvals remain unanswered. However, some recent updates suggest that progress may be on the way.

Late in 2013, FDA representatives changed their narrative related to biosimilars.¹⁴ Whereas previously they had stated that no biosimilar application had yet been filed, the agency now says that no biosimilar has yet been approved, suggesting that a manufacturer(s) may have initiated the filing process, although no official announcement has been released.¹⁴ In addition, the FDA recently announced that it expected to publish 5 guidance documents on biosimilars in 2014, including information on considerations for interchangeability, biosimilar labeling, and the duration of exclusivity for originator reference products.¹⁵ If published on schedule, these documents would help clarify the approval process.¹⁵

There’s a Lot to Consider, Start Planning Now

The implications for biosimilar evaluation, adoption, and utilization are huge for health care systems. Given the potential for differences in such things as the nonproprietary name of biosimilars, their indications, dosage forms, and data in various patient populations, pharmacists must ensure their formulary management processes can evaluate these attributes in an accurate clinical context and support appropriate use of these products.⁵ Over the next 3 to 5 years, biosimilars will represent the most direct cost savings opportunity for pharmacists. The extent to which pharmacy realizes that value depends on the degree to which we are prepared for their arrival. SPT

References

• Moody’s: AbbVie, Amgen, and Roche most exposed to biosimilar drugs market [press release]. Moody’s Investors Service; February 25, 2014. www.moodys.com/research/Moodys-AbbVie-Amgen-and-Roche-most-exposed-to-biosimilar-drugs--PR_293555. Accessed March 10, 2014.
• The global use of medicines: outlook through 2016. IMS Health; July 2012. www.imshealth.com/deployedfiles/ims/Global/Content/Insights/IMS%20Institute%20for%20Healthcare%20Informatics/Global%20Use%20of%20Meds%202011/Medicines_Outlook_Through_2016_Report.pdf. Accessed March 9, 2014.
• Statement from Ralph G. Neas, President and CEO of the generic pharmaceutical association on California Governor Brown’s veto of SB598 [press release]. Generic Pharmaceutical Association; October 12, 2013. www.gphaonline.org/gpha-media/press/statement-from-ralph-g-neas-president-and-ceo-of-the-generic-pharmaceutical-association-on-california-governor-brown. Accessed March 9, 2014.
• Manufacturing matters with biological medicines. Amgen Inc. www.buildingbiologics.com. Accessed March 11, 2014.
• Lucio SD, Stevenson JG, Hoffman JM. Biosimilars: implications for health-system pharmacists. Am J Health-Syst Pharm. 2013;70:2004-2017.
• Schumock GT, Li EC, Suda KJ, et al. National trends in prescription drug expenditures and projections for 2014. Am J Health Syst Pharm. 2014;71:e6-e23.
• Merrill J. Many new oncology drugs in 2012, with prices that test the limits. The Pink Sheet. Published online January 28, 2013.
• Haas J. Will pricing for Gilead’s Sovaldi set a ceiling in HCV, lead to a price war? The Pink Sheet. Published December 16, 2013.
• Zelenetz AD, Ahmed I, Braud EL, et al. NCCN biosimilars white paper: regulatory, scientific, and patient safety perspectives. J Natl Compr Cancer Netw. 2011;9(suppl 4):S1-S22.
• del Giglio A, Eniu A, Ganea-Motan D, Topuzov E, Lubenau H. XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of serve neutropenia and the incidence of febrile neutropenia in cycle I in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer. 2008;8:332.
• Gatzmeier U, Ciuleanu T, Dediu M, et al. XM02, the first biosimilar G-CSF, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with small cell or non-small cell lung cancer receiving platinum-based chemotherapy. J Thorac Oncol. 2009;4(6):736-740.
• Engert A, Griskevicius L, Zyuzgin Y, Lubenau H, del Giglio A. XM02, the first granulocyte colony-stimulating factor biosimilar, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with non-Hodgkin lymphoma receiving chemotherapy. Leuk Lymphoma 2009;50:374-379.
• Weise M, Bielsky MC, de Smet K, et al. Biosimilars: what clinicians should know. Blood. 2012;120:5111-5117.
• Gingery D. Is FDA reviewing a biosimilar marketing application? The Pink Sheet Daily. Published November 14, 2013.
• Guidance agenda: new and revised draft guidances CDER is planning to publish during calendar year 2014. FDA; January 31, 2014. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM314767.pdf. Accessed March 9, 2014.

About the Author

Steven Lucio, PharmD, BCPS, is senior director, clinical solutions and pharmacy program development, at Novation. He has responsibility for providing education to member organizations and supporting their efforts on various clinical practice topics including improving medication safety, mitigating the impact of drug shortages, benchmarking pharmacy costs for key drug classes, evaluating the expense of high-cost biologics, and preparing for the future development of biosimilar medications. Prior to joining Novation, Steven practiced for almost 10 years within the Baylor Health Care System in various settings, including both inpatient and ambulatory care. Steven holds a PharmD from Creighton University, a Bachelor of Science in pharmacy from the University of Texas at Austin, and is a board certified pharmacotherapy specialist. He is author of several recent publications on the topic of biosimilars.