Biosimilar manufacturers should consider working together to overcome some of the barriers that prevent biosimilars from entering the market and obtaining market share, according to Ivo Abraham, PhD, chief scientist of Matrix45 and a member of The Center for Biosimilars® Advisory Board.
Having worked in the biosimilars space from the early approvals in Europe to the market entry in the United States and the global diffusion into low- and middle-income countries, it strikes me that the uptake of biosimilars in the United States continues to lag behind both early, as well as naïve and overly optimistic, and more recent projections. True, here in the United States, we may not have the structural coverage mechanisms or soft protectionism that we see in other countries, especially those with a biosimilar manufacturing base – nor should we.
However, as the 2021 report on generics and biosimilars from the Association for Accessible Medicines tells us, 9 out of 10 prescriptions filled in the US are mostly generics and sparingly biosimilars. The United States is among the top countries worldwide in generic use. Why does biosimilar uptake lag behind?
Of course, there are some obvious factors. Laws have been passed, regulations issued, and federal pricing methods instituted that have not always been equitable to biosimilars. After dying down in Europe, misinformation campaigns about the safety and efficacy of biosimilars flew across the Atlantic in search of a new audience. As in Europe, scientists questioned the provenance of the registration trials – often with a dose of scientific xenophobia. Prolonged and complex litigation not only slowed the market entry of biosimilars but raised even more time, effort, and cost barriers to biosimilar manufacturers. Along the way, the political rhetoric of bringing down the cost of prescription medicines raged, seemingly ignorant to the 90% market share of generics.
One group of players, all competing against the same opponent, remains noticeably disorganized in the United States: the manufacturers of biosimilars – large and small, domestic and foreign, with single or multiple biosimilars approved or in the pipeline, with or without a generics arm, well-capitalized or living investment check to investment check. Quite surprising if one considers how many advocacy organizations in the United States back the use of biosimilars.
Biosimilar companies compete hard for market share – as they should do and should continue to do. More than 10 biosimilar manufacturers are on the US market, a few may join in the future, so let’s say there are 15 companies in play. Each is the other’s enemy – by way of speaking. Yet, face it: they all have a common enemy. This reminds me of growing up in Europe post World War II and during the Cold War: my enemy’s enemy is my friend – perhaps not my best friend, perhaps a bit of a false friend, but a strategic and tactical friend after all. Instead of having 14 biosimilar enemies and 1 originator enemy, why not have 14 tactical friends and only 1 enemy?
Biosimilar manufacturers in the United States should join forces on a common platform to the collective benefit of all: focused on non-competing but shared issues; bundling programmatic, legal, regulatory, and financing challenges; bolstering the safety and efficacy evidence base of biosimilars; and reinforcing the integrity, credibility, and trustworthiness of biosimilars. Five areas stand out, and some initial issues are identified.
Policy. While the 2010 Biologics Price Competition and Innovation Act (BPCIA) had many strengths, it also reflected the influence of the lobbying, intensive and extensive, by the originator industry. It is fair to say that a number of inequities in the BPCIA have hampered the approval and market entry of biosimilars. It is encouraging to see that last year, Congress passed the Advancing Education on Biosimilars Act. Less than a year ago, 2 biosimilars gained interchangeability status, though states differ in their interchangeability laws. The policy scene for biosimilars will remain challenging; however, the interest and support by both Democrats and Republicans is encouraging and refreshing.
Financing. It is unclear at this time whether external reference pricing under the Most Favored Nation Model will be resurrected or whether it will replaced by an alternate model for federal programs like Medicare. Whether or how it will be applied to biosimilars remains a topic of discussion. The presence of several biosimilars of the same originator may trigger internal reference pricing. The average sales price (ASP) for biosimilars is tied to the price of the originator product. Arguably, this benefits the originator product and may erode the ASP of biosimilar products. Commercial payers pitch biosimilars against originators, and biosimilars amongst themselves, in their formularies.
Health Equity. Disparities in health and in access to care is the black eye of American health care. Although profound structural change is essential but far in the future, biosimilars offer a cost-responsible, interim solution to increasing patient access to advanced medicines. The math is easy: cheaper drugs save money. The question is, what do we do with the savings? As our group has shown for 10 years now, savings generated from biosimilar conversion can be parlayed, on a budget-neutral basis, into expanded access for patients. More patients could receive expensive treatments; say, novel immunotherapies for cancer that have not yet lost protection. Even better, more patients could be treated with biosimilars. For instance, breast cancer patients could be treated with a biosimilar trastuzumab or colorectal cancer patients with a biosimilar bevacizumab. Pay less, treat more.
Evidence. Though the misinformation messaging has abated, the call for more and better evidence on biosimilars should be heeded. This should be done collectively by the biosimilar industry rather than piecemeal biosimilar-by-biosimilar and manufacturer-by-manufacturer. It should be done with the statistical power of well-designed observational studies and registries, rather than alarmic case reports and case series. It should be forward-looking rather than defensive, pre-emptive rather than reactive. The pan-European MONITOR-GCSF trial assessing a biosimilar filgrastim in cancer and the MONITOR-CKD5 trial evaluating a biosimilar erythropoietin in end-stage renal disease that we helped Sandoz design, implement, and disseminate in the late 2000’s to early 2010’s reassured clinicians, payers, and patients of the safety and efficacy of these 2 biosimilars. More broadly, the studies provided an evidence base and reference point for the subsequent breakthrough of biosimilars in the European marketplace. These studies also demonstrated the scientific potential of biosimilars: answering new questions with older products.
Tort. If originator TNF-αinhibitors such as originator infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel) are any indication, it may only be a matter of time until biosimilars of these agents will be the subject of spill-over malpractice lawsuits because of the risk of malignancies, serious infections, lupus, among other diseases. In the worst case, we may see “extortion” litigation: law firms (yes, the type that advertises on roadside billboards, bus stop benches, public transportation, and late-night cable) threaten litigation or file a lawsuit, seek a “quick flip” settlement, and pocket their 30% to 45% contingency fee. Building a collective safety and efficacy repository of data and evidence on biosimilars, at the class level, will prove to be an effective and affordable approach to thwart or respond to litigation.
Maybe we should get the dialogue among biosimilar manufacturers going. Will anyone be at the American Society of Clinical Oncology meetings in Chicago in early June?
Ivo Abraham is chief scientist of Matrix45 and professor of pharmacy, medicine, and clinical translational sciences at the University of Arizona, where he is associated with the Center for Health Outcomes and PharmacoEconomic Research. He has worked in biologic drugs since the late 1990s and in biosimilars since their introduction in the European marketplace – collaborating closely with Karen MacDonald, who is also his wife. On both the private and academic sides, his group published the first economic evaluations of biosimilars, a line of studies that continues to date. Building on large international observational studies on biological therapies that the Abraham-MacDonald tandem implemented in the late 1990s and early 2000s, they worked with Sandoz on the MONITOR-GCSF and MONITOR-CKD-5 studies that proved to be instrumental in the breakthrough of biosimilars in Europe. As biosimilars entered the US market, Matrix45 added studies in support of biosimilar adoption in the United States. More recently, Matrix45 has ventured into biosimilars in emerging markets, including low- and middle-income countries. He may be reached at email@example.com.
Statement of Disclosures of Relevance to this Column
Matrix45 as well as predecessor companies in which I hold or held equity have been contracted for research, analytics, dissemination, and consulting services by Janssen/Johnson&Johnson, Amgen, Novartis, and Roche on the originator side and by Sandoz/Novartis, Coherus Biosciences, Mylan/Viatris, Hospira/Pfizer, and Teva on the biosimilars side; with past and current conversations with Merck KGaA, Celltrion, Apobiologix, Apogenix, Fresenius Kabi, and Spectrum. By company policy, associates of Matrix45 cannot hold equity in sponsor organizations, nor provide services or receive compensation independently from sponsor organizations. Matrix45 provides its services on a non-exclusivity basis.