Having worked in the field of biosimilars from first approvals in Europe to market entry in the United States and global uptake in low- and middle-income countries, I am struck by the fact that the uptake of US biosimilars continue to lag behind both early, as well as naive and overly optimistic, and more recent projections. Granted, here in the United States, we may not have the structural hedging mechanisms or soft protectionism that we see in other countries, especially those with a biosimilar manufacturing base – we shouldn’t no more.

However, as the report 2021 on Generics and Biosimilars from the Association for Accessible Medicines tells us that 9 out of 10 prescriptions filled in the United States are mostly generics and few biosimilars. The United States is among the first countries in the world to use generics. Why is biosimilar uptake lagging?

Of course, there are obvious factors. Laws have been passed, regulations published, and federal pricing methods instituted that have not always been fair to biosimilars. After dying out in Europe, disinformation campaigns about the safety and efficacy of biosimilars have crossed the Atlantic in search of a new audience. As in Europe, scientists have questioned the provenance of the recording trials – often with a dose of scientific xenophobia. Protracted and complex litigation has not only slowed biosimilar market entry, but has also removed even more hurdles in terms of time, effort and cost for biosimilar manufacturers. Along the way, political rhetoric aimed at lowering the cost of prescription drugs has raged, seemingly ignoring the 90% market share of generics.

One group of players, all competing against the same adversary, remains noticeably disorganized in the United States: biosimilar manufacturers – large and small, domestic and foreign, with one or more biosimilars approved or in the pipeline, with or without a generic arm , well capitalized investment check or living to investment check. Quite surprising considering the number of advocacy organizations in the United States that support the use of biosimilars.

Biosimilar companies are competing hard for market share – as they should and should continue to do. There are over 10 biosimilar makers in the US market, a few may join in the future, so let’s say there are 15 companies in play. Each is the enemy of the other – so to speak. Yet, let’s face it: they all have a common enemy. It reminds me of my childhood in Europe after the Second World War and during the Cold War: the enemy of my enemy is my friend – maybe not my best friend, maybe a bit of a false friend, but a strategic and tactic after all. Instead of having 14 biosimilar enemies and 1 original enemy, why not have 14 tactical friends and only one enemy?

Biosimilar manufacturers in the United States should join forces on a common platform for collective benefit: focused on non-competitive but shared issues; bring together programmatic, legal, regulatory and financial challenges; strengthen the evidence base for the safety and efficacy of biosimilars; and enhance the integrity, credibility and reliability of biosimilars. Five areas emerge and some initial issues are identified.

Policy. While the Biologics Price Competition and Innovation Act (BPCIA) of 2010 had many strengths, it also reflected the influence of intensive and extensive lobbying by the originator industry. It is fair to say that a number of inequities in the BPCIA have hindered the approval and market entry of biosimilars. It is encouraging to see that last year Congress passed the Advancing Biosimilars Education Act. Less than a year ago, 2 biosimilars were granted interchangeability status, although states differ in their interchangeability laws. The political scene for biosimilars will remain difficult; however, the interest and support from Democrats and Republicans is encouraging and refreshing.

Funding. It is unclear at this time whether external benchmark pricing under the most favored nation model will be resurrected or replaced with an alternative model for federal programs like Medicare. Whether or how it will be applied to biosimilars remains a matter of discussion. The presence of several biosimilars of the same originator can trigger internal reference pricing. The average selling price (ASP) of biosimilars is linked to the price of the originator product. Arguably, this benefits the originator product and may erode the ASP of biosimilars. Commercial payers present biosimilars against originators, and biosimilars against each other, in their formularies.

Health Equity. Disparities in health and access to care are the dark eye of American health care. While deep structural change is essential but far in the future, biosimilars offer a cost-effective middle ground to increase patient access to cutting-edge medicines. The math is simple: Cheaper drugs save money. The question is, what do we do with the savings? As our group has shown for 10 years now, the savings generated by the conversion of biosimilars can be transformed, without impact on the budget, into expanded access for patients. More patients could receive expensive treatments; say, new cancer immunotherapies that haven’t lost their protection yet. Even better, more patients could be treated with biosimilars. For example, breast cancer patients could be treated with a biosimilar trastuzumab or colorectal cancer patients with a biosimilar bevacizumab. Pay less, process more.

Proof. Although misinformation messages have diminished, the call for more and better evidence on biosimilars needs to be heard. This should be done collectively by the biosimilar industry rather than on a piecemeal biosimilar-by-biosimilar and manufacturer-by-manufacturer basis. This should be done with the statistical power of well-designed observational studies and registries, rather than alarming case reports and case series. It must be prospective rather than defensive, preventive rather than reactive. The pan-European MONITOR-GCSF trial evaluating 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 from the late 2000s in the early 2010s reassured clinicians, payers and patients of the safety and efficacy of these 2 biosimilars. More generally, the studies provided an evidence base and benchmark for the subsequent breakthrough of biosimilars in the European market. These studies also demonstrated the scientific potential of biosimilars: answering new questions with older products.

Offense. If the original TNF-α inhibitors such as the original infliximab (Remicade), adalimumab (Humira) and etanercept (Enbrel) are any indication, it may just be a question. long before biosimilars of these agents are subject to malpractice suits. due to the risk of malignant tumors, serious infections, lupus, among other diseases. In the worst case, we can witness the “extortion litigation: law firms (yes, the guy who advertises on roadside billboards, bus stop benches, public transport and late-night cable) threaten to sue or sue, seek a “quick” settlement, and pocket their 30% to 45% contingency fee. Creating a collective repository of data and evidence on the safety and efficacy of biosimilars, at the class level, will prove to be an effective and affordable approach to thwarting or responding to litigation.

Maybe we should start the dialogue between the manufacturers of biosimilars. Will anyone be at the American Society of Clinical Oncology meetings in Chicago in early June?

Organic

Ivo Abraham is Matrix45’s Chief Scientist and Professor of Pharmacy, Medicine, and Clinical Translational Sciences at the University of Arizona, where he is a Fellow in the Center for Health Outcomes and PharmacoEconomic Research. He has been working on biologics since the late 1990s and on biosimilars since their introduction to the European market – working closely with Karen MacDonald, who is also his wife. Both privately and academically, his group published the first economic evaluations of biosimilars, a line of studies that continues to this day. Building on extensive international observational studies of biological therapies that the Abraham-MacDonald tandem implemented in the late 1990s and early 2000s, they worked with Sandoz on the MONITOR-GCSF studies and MONITOR-CKD-5 which have proven instrumental in the breakthrough of biosimilars in Europe. When biosimilars entered the US market, Matrix45 added studies supporting the uptake of biosimilars in the US. More recently, Matrix45 has ventured into biosimilars in emerging markets, including low- and middle-income countries. He can be contacted at [email protected]

Statement of relevance disclosures for this column

Matrix45 and predecessor companies in which I own or had an equity interest were engaged for research, analysis, dissemination and advisory 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 for biosimilars; with past and current conversations with Merck KGaA, Celltrion, Apobiologix, Apogenix, Fresenius Kabi and Spectrum. It is company policy that Matrix45 associates may not hold stock in sponsoring organizations, or provide services or receive compensation independently of sponsoring organizations. Matrix45 provides its services on a non-exclusive basis.