In 2006, the European Union approved its first biosimilar drug. Now, more than a decade later, the United States and its FDA continues to struggle with how to incorporate these unique pharmaceutical treatments into mainstream medical practice. The complex and organic nature of these biological drugs makes it difficult to test and approve them in a traditional setting—biosimilar treatments will need to gain some degree of acceptance in at least 1 of 4 distinct medical and scientific communities before they can enter the mainstream. Physicians, pharmacists, patients, and health plans will play key roles in the eventual uptake of biosimilars by the broader marketplace, and each population must be reached in a very targeted way.
Perhaps the biggest obstacle to biosimilar uptake is the broad lack of familiarity with these medicines in most disciplines. For example, despite the fact that biologic and biosimilar drugs have played a vital role in cancer treatment over the past decade in Europe, a 2011 survey of oncologists in found that about 1 in 4 doctors had never heard of biosimilar drugs and more than half admitted that they had “no or slight familiarity” with these treatments.
“People are not going to purchase or prescribe something they do not understand,” said Joseph P. Fuhr, Jr, PhD, professor emeritus at Widener University and member of The Center for Biosimilars editorial board.
“We have a lot of work to do on education,” added Molly Leber, PharmD, BCPS, FASHP, a manager of medication policy and formulary management in the Yale New Haven Health System who also serves on the editorial board at the Center for Biosimilars. “There are numerous surveys that have shown healthcare professionals and patients don’t know about the current drug approval process [for biologics] and even less about biosimilars.” Leber added that many healthcare professionals still have concerns about the safety of biosimilars because of the general lack of awareness about the approval process, and that patients often do not realize that there are alternatives to their current biologic therapies.
While the expanding presence of oncological biosimilars and biologics in the US marketplace will bring these drugs more to the forefront of the prescribing physician’s mind both in oncology and elsewhere, there are certainly some roadblocks to overcome before they become anything other than a last resort. Many physicians who are familiar with biosimilar and biologic drugs still tend toward prescribing more familiar treatment options because biosimilars feel risky; a biosimilar’s corresponding biologic often bears the full weight of testing and trials with the result that the “confirmatory trials” for biosimilar safety required by the FDA may feel inadequate. It is, in fact, the case that for biosimilars the weight of proof of safety and efficacy lies largely within the proof of similarity to a biologic. Further complicating the prescription process, because biosimilars are organic and their effects may evolve in a patient who takes them over time, physicians may be reluctant to prescribe a treatment that feels unpredictable to both the patient and themselves.
Brian Lehman, MBA, MHA, RPh, manager of pharmacy benefits and policy in Columbus, Ohio, also on the editorial board for The Center for Biosimilars, described the oncology sector as one most likely to be impacted in the near term by biosimilar uptake. “The oncology community is currently impacted by the biosimilar Zarxio (filgrastim) that has been available on the market since September 2015,” he observed. Zarxio bolsters the immune system and helps a patient’s body overcome infection. Lehman further noted that there are 3 additional biosimilars in the oncology pipeline: those for Neupogen, Neulasta, and Procrit/Epogen. “The biosimilar pipeline is robust,” he said, adding, “the FDA has 66 biosimilar programs for 20 different reference products.”
Furthermore, given that oncology drugs are “some of the highest-priced drugs available,” as Fuhr described them, the introduction of biosimilars will likely “increase access and improve quality of life for many patients,” he said.
In order to reach the prescribing population and generate momentum for biosimilar uptake in this sector, physicians must understand how valuable these drugs may be from both a treatment standpoint and an accessibility standpoint. While effective treatment is certainly vitally important, the relatively lower cost of biosimilar drugs will, of necessity, also play a role in their uptake. However, there is some debate about how affordable biosimilar drugs will actually be compared to their biologic counterparts. “Lower prices and greater access will benefit consumers and help decrease prices in the healthcare market,” observed Fuhr, adding that this will also motivate “innovators” to “attempt to find new drugs as profits on old drugs decline.”
Lehman agreed, stating, “The greatest benefit [of biosimilar uptake] would be increasing patient access to more affordable life-changing and even life-saving biologic drugs.”
Not all sources agree that biosimilar uptake will lead to more affordable treatments, however. Currently, biologic drugs account for about 62% of Medicare spending in the United States, compared to about one-third in 2005. It is to be hoped that biosimilar treatment options might make biologic results available to populations that either might not be able to afford them or that might not be prescribed to them first due to cost issues. This in itself presents another uptake issue, however, since conventional wisdom predicts that biosimilar drugs should cost about 30% less than their biologic counterparts but, thus far, these drugs are debuting at more of a 15% discount. This is due, in large part, to the costs of testing and proving similarity of these drugs.
Over the next 4 years, a large number of biologic patents will expire, expanding biosimilar development and production options. This could increase competition in the marketplace and drive biosimilar prices down to that benchmark 30% discount. If it does not, however, physicians and government bodies that fund many of their prescriptions will continue to find it difficult to prescribe these treatments when more conventional options exist.
Pharmacists and Biosimilar Interchangeability
Along with the prescribing community, pharmacists could play a major role in the uptake of biosimilar drugs that receive an FDA approval for interchangeability. For example, in Great Britain, the British Oncology Pharmacy Association (BOPA) has issued a “welcome statement” to biosimilars that states, in part, that biosimilars can and should be used in place of more expensive biologic treatments when possible. For example, according to BOPA, Rituximab, a biologic used to treat non-Hodgkin’s lymphoma, currently costs the country’s National Health Services about $209 million each year. Medical economists speculate that a biosimilar to Rituximab could save what BOPA called a “significant” amount of money that could be “reinvested into innovation and patient services.” In the United States, a similar attitude from healthcare law- and policy-makers will play a huge role in whether or not pharmacists are willing, when possible, to prescribe a biosimilar in place of the reference biologic.
“The best-case scenario would be if biosimilars can be incorporated into the healthcare system the same way that generic drugs are,” said Leber, elaborating that this would enable biosimilars to create the cost-savings their proponents say will come with their uptake: through competition. She added, “If you look at the European experience, there has been a significant decrease in the drug cost and increase in prescription volume.” Lehman agreed, observing, “Ideally, biosimilars will provide significant savings relative to the cost of the reference product, but there is also a need to balance and monitor for the potential and unintended consequence of discouraging some manufacturers from bringing more biosimilar competition to the US market.”
Influence of an Educated Patient
At the end of the day, it may well be the patient population that is most receptive to biosimilars because their concerns are less complex than those of prescribers and pharmacists. In one particular biosimilar trial, researchers asked the question: “Would you use [this biosimilar] for your mother if she had ERBB2-positive breast cancer?” They concluded, “The answer should be ‘yes.’” The patient population will ultimately be concerned with 2 main issues regarding biosimilars: efficacy and affordability/accessibility. Manufacturers may opt to reach past physicians and pharmacists directly to the patient population in order to solicit requests from patients for these treatments and to smooth the prescription process for physicians. If patients requiring these treatments can be educated about their efficacy, safety, and affordability, then many roadblocks in other populations are likely to erode on their own.
“Patients need education in order to feel confident that a biosimilar is just as safe and effective as the reference product,” said Lehman, citing European statistics including “over 400 million patient days of safe and effective treatment using biosimilars since the first biosimilar was approved and marketed in 2006.”
Although acceptance of biosimilars in the medical marketplace is largely an issue of educating the appropriate populations about biosimilar topics most relevant to them, there is one potential roadblock to uptake that is largely administrative yet possibly far more substantial than any other: nomenclature. It is not accurate to equate biosimilars to generics in terms of their associated biologics, although it may be helpful to do so to a limited extent when attempting to educate the general public about them. Because biosimilars are not generics of biologics, however, they are difficult to name and track within the medical billing system. At present, when a drug enters the mainstream and physicians begin prescribing it, the long-term effects of that drug can, to a degree, be tracked through the medical billing system. Data in the system can be reviewed to examine effects on subpopulations of patients and potential problems and benefits may be identified. However, biosimilars cannot be named the same way as generics, which have names that link them back to the brand-name drug, and also have a four-letter suffix that, according to the FDA, has no meaning other than that it is unique to that specific biosimilar. This will prevent inadvertent substitutions and support safety monitoring, but it will dramatically complicate how the drugs are processed through medical billing and could inhibit prescribers’ and pharmacists’ willingness to promote biosimilar use. “Formulary decisions are going to be complex,” Leber warned.
If biosimilar uptake does not gain momentum in the next decade the entire biosimilar industry could be derailed. In the event that it is too expensive to bring these treatments to market and achieve uptake in the medical sector, manufacturers may opt to pursue other treatment models. Of course, runaway successes of biologics like Genentech’s Xolair (omalizumab), a treatment for allergic asthma that became a blockbuster drug in 2014, could entice manufacturers to continue research and development as long as the biosimilar industry continues to evolve in the public eye and the view of the medical population.
Biosimilars are demonstrably safe, effective, and affordable relative to their biologic counterparts. Conveying that message to the various stakeholders: physicians, pharmacists, and patients, is the linchpin to biosimilar uptake in the United States in the next decade.