Oncology supportive care, oncology, and immunology biosimilars make up the 3 main classes of biosimilars that have emerged on the US market. However, rates of uptake are vastly different owing to a variety of factors.
To date, 46% of the 26 FDA approved biosimilars have come to market in the United States. The 12 launched products have experienced challenges with uptake, at first largely attributed to the uncertainty around biosimilars. Now 5 years since the introduction of the first biosimilar, Zarxio (filgrastim), uptake remains a challenge for a multitude of reasons, including payer support, stakeholder education, and patent dances. To date, 3 main classes of biosimilars have emerged in the United States. There are some key similarities and differences across these categories that have impacted utilization and continue to do so.
Oncology Supportive Care
Colony-stimulating factors (CSFs) were the first biosimilar entrants in the US market. In total, there are 3 biosimilars for reference pegfilgrastim (Neulasta) and 2 for the originator filgrastim (Neupogen). Zarxio, a CSF, became the first biosimilar on the US market when it launched in September 2015. To date, it has a market share of roughly 50%. Biosimilars to Neulasta are increasing in share, such as Udenyca (pegfilgrastim-cbqv), which has captured a roughly 20.5% market share since launching in January 2019.
In terms of gaining market share, the oncology supportive care biosimilars have fared well compared with other classes. Fewer market barriers have allowed for more entrants. Clinically, these products are short-term therapies resulting in a quick therapeutic effect, such as an increase in red or white blood cells. As a result, stakeholders have generally been accepting of these agents. Payers such as Prime Therapeutics have preferred biosimilar CSFs over reference products, and healthcare professionals are prescribing them, leading to improved market share.
The immunology class has seen the most approvals with 5 adalimumab, 4 infliximab, and 2 etanercept biosimilars. However, only 2 infliximab biosimilars are available in the United States. Inflectra (infliximab) was the first infliximab biosimilar to launch in this market, followed by Renflexis (infliximab); together, these have captured only an estimated 12% of the total infliximab market share, which is far less than for CSF agents.
Market penetration in immunology has been challenging for biosimilars due to many factors. For one, this class is one of the most competitive across the board, with many agents including anti-TNFs and anti-interleukins. Biosimilars face competition from reference products, other anti-inflammatories, and even biosimilars.
Biosimilar launches have experienced delays due to litigation challenges. Reference adalimumab (Humira) has an extensive patent library and, therefore, biosimilar launches are delayed until 2023. Etanercept biosimilars face similar barriers and may not be expected until 2029.
Compared with CSFs, immunology biosimilars have seen less stakeholder acceptance. The indications of rheumatology, inflammatory bowel diseases (IBD), and psoriasis are chronic conditions requiring long-term treatment. Patients and prescribers are hesitant around the efficacy of biosimilars, as a response to treatment (eg, remission) is not immediate. Further there is a concern about switching stable patients from a reference biologic to a biosimilar due to immunogenicity, even though many real-world data from Europe, including findings from the NOR-SWITCH study, generally show similar efficacy and safety without an increase in immunogenicity.
Another key challenge for prescribers has been indication extrapolation. Biosimilars do not undergo robust clinical studies for all approved indications, and prescribers may be less accepting of biosimilars in these indications due to a lack of clinical data.
Although payers generally favor biosimilars due to the potential for cost savings, biosimilars have failed to fully integrate in immunology. Aggressive contracting by reference manufacturers, such as Johnson & Johnson has done for Remicade (infliximab), has limited biosimilar uptake. However, the payer push for biosimilars has improved in some cases; United Healthcare Medicare Advantage now prefers the infliximab biosimilars Inflectra and Renflexis.
Biosimilars in oncology are the latest entrants, with 8 product launches since 2019. Although barriers to uptake remain, the experience of biosimilars in immunology does not directly translate here. Since launch, oncology biosimilars have been able to capture a sizeable market share. For example, Amgen’s oncology biosimilars, Mvasi (bevacizumab) and Kanjinti (trastuzumab) have achieved a 15% and 17% market share for trastuzumab and bevacizumab, respectively. Payers such as United Healthcare have also started including oncology biosimilars to formularies. United Healthcare is accelerating utilization.
There remain concerns around indication extrapolation. For instance, clinical trials to demonstrate biosimilarity for rituximab biosimilars were conducted in rheumatoid arthritis rather than oncology, leading to an absence of oncology data. As rituximab bevacizumab and trastuzumab are approved across many indications, therapeutic response data take time as key oncology end points focus on survival; as a result, prescribers may hesitate to extrapolate findings across indications. The absence of oncology-relevant data also means there is a lack of immunogenicity data, which has been a mainstay concern around biosimilars.
Thus far we have seen 3 key classes of biosimilars emerge, each with a different commercial trajectory. The CSF biosimilars have had a growing market share over the years with relatively good acceptance by healthcare stakeholders. On the other hand, biosimilars have seen limited market penetration in immunology, although it is the largest market. Perhaps the sluggishness of acceptance and utilization will change once biosimilars for adalimumab enter and as more real-world data are generated from Europe around tumor necrosis factor inhibitors. The oncology class of biosimilars has seen success in early days of product launches, which signifies an accelerating US market.
Biosimilar manufacturers should continue to educate and generate real-world data on biosimilars, especially in challenging categories such as immunology. This, alongside a greater payer shift toward biosimilars, continues to prime the US market for biosimilar uptake.