Preparing for the third decade of biosimilars

KEYWORDS:

• biosimilars
• generics
• pharmacoeconomics
• affordable healthcare
• innovation

It has been 17 years since the approval of the first biosimilar in Europe (Omnitrope®, somatropin) and only 8 years since the approval of the first biosimilar in the US (Zarxio®, filgrastim). As of this writing, 75 biosimilars have been launched in the European Union and 37 (out of 41 approved) in the US [1]. The European portfolio is broader than the US, at least at this time, and includes biosimilar versions of several hormonal agents, granulocyte-stimulating growth factors, erythropoiesis-stimulating agents, anti-angiogenic agents, anti-tumor necrosis factor agents, anticoagulants, insulins, immunosuppressive agents, and various monoclonal antibodies used to treat solid and hematological malignancies. The pipeline goes even deeper as the patents of, for instance, the CTLA-4, PD-1, and PD-L1 inhibitors that have revolutionized cancer care lose exclusivity in the coming years.

It has not been a smooth path, at least not initially. Similar to when generic versions of small-molecule agents emerged in the 1960s, there were concerns, if not fears, about the (presumed) unknowns of biosimilars. Some of these were clinically understandable (efficacy, effectiveness, and safety), yet some were fueled by misinformation spread by stakeholders who shall remain unnamed.

In retrospect, the parallel to generics may have been helpful and may have helped overcome the reluctance on the part of clinicians and patients to accept biosimilars. However, perhaps the greatest force to biosimilar adoption have been the payers – in markets with national public health insurance systems as well as in markets with a mix of public and private/commercial payers. Biosimilars are (or should be) cheaper, which generates savings – something payers like. This creates another opportunity for payers: to use these savings to provide, on a budget-neutral basis, expanded access to care to patients who might otherwise not receive care, as simulation studies over the past decade have shown for both high-income [2,3] and middle-income countries [4]. For instance, these savings could be applied to treat more cancer patients with novel agents that still have exclusivity and for which no cheaper biosimilars are available.

Especially in recent years, the biosimilar industry has come to realize some hard and harsh realities, as I have discussed in a series of columns on the Center for Biosimilars website [5]. What should be the evidence base for approval? Should Phase 3 trials be required or should demonstration of pharmacokinetic and/or pharmacodynamic comparability of the biosimilar to its reference be sufficient, as the World Health Organization argues in its revised 2022 biosimilar guideline [6]? How should biosimilars be priced to enable fair reimbursement and fair competition of biosimilar and reference alike? Should competitive price erosion be avoided, considering that biosimilar manufacturers have development and other pre-market expenses to recover? Should biosimilar manufacturers coalesce in an advocacy organization that differentiates and promotes its industry – as opposed to merely competing against each other for market share? And, very importantly, are biosimilar manufacturers ready to accept that biosimilars are commodities and that biosimilar markets are commodity markets: a market of interchangeable products. Who produced the commodity is of little regard. As we have seen with generics, in time, brand name will be of limited relevance. The lower the price, the better. Slim profit margins. Volume contracts. This begs a sensitive question: is there room for 10 adalimumab or 6 pegfilgrastim or 5 trastuzumab biosimilars in the US? Conversely, how many should there be to assure competition and keep products affordable?

Does this mean that some biosimilars or, worse, some manufacturers may not make it through the upcoming third decade? The future may indeed look rather grim if the market does not expand beyond the current 1 billion people: the high-income countries of Northern, Western, Central, and Mediterranean Europe; North America; Oceania; East Asia; and the Middle East. Indeed, the sustainability of a biosimilar commodity market will depend on the other 7 billion people in the world, starting with the many middle-income countries with good health-care systems and in time encompassing low-income countries, including sub-Saharan Africa. The future sustainability, commercial and humanistic, of biosimilars lies well beyond the high-income countries. Biosimilars will prove to be the channel to bring biological treatment to the rest of the world.

These questions are the major drivers of this third Special Issue on biosimilars of Expert Opinion on Biological Therapy. A first section casts a broad geographic net as several Perspective papers focusing on underserved regions of the world were solicited. A first paper [7] addresses dynamics between the economics of biosimilars and challenges in the adoption of biosimilars to address unmet clinical needs in low- and middle-income countries (LMIC). Subsequent papers take a regional look at biosimilars, starting with Latin America, where biosimilars have already gained some traction and where some countries have a nascent biosimilar industry [8]. In fact, Latin America might prove to be a case in point where local or regional biosimilar manufacturers need to be fostered independently but also where distributors need to be better aligned and deployed to support larger global manufacturers of biosimilars. This is followed by a paper reviewing the opportunities and challenges in several of the LMICs of the Middle Eastern and North African (MENA) region [9]. Staying, geographically (but not economically) speaking, in the Middle East, a paper on biosimilars in Saudi Arabia is a case study in how an affluent country with high access to medical care is restructuring its health sector so that it can provide high-quality but value-based health care – biosimilars being a key channel in this regard [10]. With one of the world’s largest (potential) biosimilar markets and home to well-established and well-regarded generics and biosimilars industries, a paper from the South Asian region presents a case study of how biosimilar agents, current and future, could have a major impact on the management of endemic vascular diseases of the retina [11]. A team from India also discussed the global uptake of insulin biosimilars and the steps that need to be taken to expand their use [12]. Unfortunately, we were unable to find experts willing to write on biosimilars in sub-Saharan Africa, but will endeavor to do so as a later add-on. The second section of this Special Issue consists of 15 contributed papers on clinical studies at various stages of development, from the very early to the post-approval. Collectively, these articles reflect the ongoing work in developing biosimilars and bringing them to market in various regions of the world.

The third decade of biosimilars will be challenging. Not only are pronounced market share struggles in the current ‘1 billion’ biosimilar markets likely but the biosimilar industry will need to expand beyond the borders of its current markets. In addition, another class of competitors to both originators and their biosimilars is on the horizon, especially in the immuno-oncology space. I would like to call them bioparallels: new biological molecules (for instance, PD-1 inhibitors) without the ambition of being early-in-class innovators but later-in-class replications instead, approved not on the basis of biosimilar approval pathways but as new biological agents and intending to be lower-priced market disruptors, just like biosimilars but also competing with biosimilars.

Declaration of interest

I Abraham currently holds equity in Matrix45, LLC and has held equity in predecessor companies, which have been contracted for research, analytics, dissemination, consulting, and training services related to biosimilars as well as their referencing originators by Janssen/Johnson&Johnson, Amgen, Novartis, and Roche on the originator side and by Sandoz/Novartis, Coherus Biosciences, Mylan/Viatris/Biocon, Hospira/Pfizer, and Teva on the biosimilars side; with past and current conversations with Celltrion, Fresenius-Kabi, Merck KGaA, Apobiologix, and Apogenix. Matrix45, LLC also has been contracted by the Eastern Research Group for advisory services related to a US federal study on the cost of bringing biosimilars to market. According to 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. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

I wish to thank Alice Bough, Commissioning Editor, Expert Opinion on Biological Therapy, for her expertise and work on realizing this Special Issue on biosimilars.

Additional information

Funding

This paper was not funded.