Sonia T. Oskouei, PharmD, BCMAS, DPLA, is vice president of Biosimilars for Cardinal Health.

Sonia T. Oskouei, PharmD, BCMAS, DPLA

The evolution of biosimilars so far in the United States has revealed one thing for certain: Generalizations cannot be made about biosimilar market dynamics across different therapeutic areas. Although therapeutic oncology biosimilars gained significant market share in the year after they became available, adoption of infliximab biosimilars in rheumatology over the past few years has been sluggish at best. As products in other therapeutic areas make their way through the development pipeline, questions remain about how quickly uptake will occur. One therapeutic area to watch in the coming year is ophthalmology.

Ophthalmology biosimilars, specifically anti–vascular endothelial growth factor (VEGF) agents, are poised to compete with some of the most commonly used therapies for neovascular (eg, wet) age-related macular degeneration (AMD). With Samsung/Biogen’s FDA filing for SB11 (a ranibizumab biosimilar) in November 2020, and with several more candidates in the pipeline, biosimilars are about to make an impact on the ophthalmology market.

AMD is the leading cause of irreversible visual impairment in people aged 60 and older and is projected to affect over 288 million people globally by 2040 as the population ages. It is an eye disease that affects the macula (the central area of the retina), resulting in the loss of sharp central vision. Without central vision, people are unable to carry out critical daily activities such as reading, driving, and recognizing faces, which can lead to an overall decline in quality of life. In addition to lowering quality of life, AMD is associated with significant economic and treatment burdens for patients, as current management strategies include frequent monitoring and recurrent intravitreal injections with anti-VEGF agents. It is estimated that the US annual economic burden from direct health care costs due to AMD is $4.6 billion.

Three of the most common treatment options for AMD include anti-VEGF agents: ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin, off-label).

 Bevacizumab has been used off-label for several years by being repackaged by compounding facilities for intravitreal administration.

 Both Lucentis and Eylea have multiple biosimilar candidates in development by various manufacturers, but there are no approved biosimilars for these agents. In the case of Avastin, biosimilars are already approved and available on the market, but the role of bevacizumab biosimilars in ophthalmology is unclear. Known utilization has been for on-label oncology indications.

To gain early insight into levels of awareness and perspectives on the role of biosimilars in ophthalmology, Cardinal Health conducted research via a series of survey questions with community-based retina specialists (N = 37) from across the country. Interim results of the survey revealed significant opportunities to help prepare the market for the entrance of ophthalmology biosimilars. When asked about their familiarity with biosimilars, 31% of physician respondents (29 total responses) said they are not very familiar with biosimilars, and more than half (55%) said they have read research about them but are not familiar with the specifics, such as manufacturing, approval processes, and clinical trial design. However, the majority of respondents (83%) perceive biosimilars as fitting into the treatment armamentarium to help keep drug costs down (29 total responses), and more than half of respondents said they would consider using a ranibizumab biosimilar or aflibercept biosimilar once they become available.

When asked what their primary concern with prescribing ophthalmologic biosimilars would be, 43% responded they would be uncomfortable from a clinical standpoint and 35% responded with payer coverage concerns. These responses serve as critical reminders that, when it comes to driving biosimilar adoption, it is important to provide proactive education to all key stakeholders, including providers, practice administrators, payers, and patients. For example, payers, and strategies such as step-therapy, will play a significant role in the ability to adopt ophthalmology biosimilars. Therefore, early payer engagement and education are critical to support clinically and financially sound formulary decisions that are best for patients and practices. Topics including the regulatory approval pathway and clinical trials structure and terms, such as extrapolation and interchangeability, are important in developing stakeholder familiarity and confidence in biosimilars. In fact, the vast majority of provider survey respondents said they would like to receive more educational information about the safety, efficacy, and performance of biosimilars (

Although the trajectory for ophthalmology biosimilars in the United States is still unknown, there are key lessons that can be applied from current and past experiences to better prepare the market for the launch of the first ophthalmology biosimilar. Education should be at the forefront of this drive. As the country prepares for the market entrance of the first ophthalmology biosimilar, the time to focus on educational efforts is now. Biosimilars are poised to bring significant cost savings to help mitigate the financial burden associated with the management of AMD, and in order to realize the full benefits of these agents, providers, payers, and patients must be well equipped to evaluate and adopt them as soon as they hit the market.

Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. 

. 2016;3:34. doi:10.1186/s40662-016-0063-5

Holekamp NM. Review of neovascular age-related macular degeneration treatment options. 

. 2019;25(1suppl 10):S172-S181. www.ajmc.com/view/review-of-neovascular-agerelated-macular-degeneration-treatment-options

Cardinal Health. 2020. Cardinal Health survey of US retinal specialists. Internal report. Unpublished.

Articles

Samsung Bioepis has filed for FDA approval for a ranibizumab biosimilar candidate (SB11), and more ophthalmology biosimilars are in the pipeline. 

Opinion: Is the Ophthalmology Market Ready to Embrace Biosimilars?

Rheumatoid arthritis (RA) is one of the most rapidly growing and evolving therapeutic areas, with the global market for RA drugs 

The United States is expected to have the most rapid growth of any country due to increased awareness and prevalence of RA among an aging population. As the country nears its 4-year anniversary of having an infliximab biosimilar on the market (Inflectra, November 2016), significant barriers to biosimilar adoption still persist. Inflectra and Renflexis (launched July 2017) can be viewed as the more “seasoned” biosimilars in the United States, given that most FDA biosimilar approvals and launches have occurred just within the past couple years. However, time on the market does not strongly correlate with adoption: Biosimilars still have less than 10% of the overall market for infliximab molecules.

To take a deeper dive into one of the fastest growing categories of specialty medicines, Cardinal Health Specialty Solutions has produced a Rheumatology Insights 

 that includes results from a survey of over 100 US-based rheumatologists on their perceptions and experiences with biosimilars in rheumatology thus far.

An overwhelming number of rheumatologists surveyed (98%) were familiar with biosimilars, and (90%) felt comfortable prescribing them to their patients. However, the majority (66%) were unlikely to switch their patients from the reference products to biosimilars until there was greater adoption of biosimilars among payers.

Interchangeability and extrapolation continue to create hesitation among providers; and when asked about top concerns with prescribing biosimilars, efficacy was the leading response. These findings are aligned with both 

investigations conducted over the past year that showed rheumatologists understand biosimilars but lack confidence to use them.

In addition to the payer landscape, which has been a frequently cited barrier to US biosimilar adoption, there is a continued lack of clinical confidence among rheumatologists, recent findings show. This highlights the significant need for additional real-world evidence (RWE) on biosimilar utilization. As more providers and patients gain experience with switching to biosimilars, stakeholder support for the abbreviated 351(k) FDA approval pathway, which provides certification for safety and efficacy equivalence to the reference product, will be further strengthened. Additionally, peer-to-peer knowledge sharing will continue to be critical in building confidence in biosimilars, including the concept of extrapolation. In fact, multiple studies have found that physician adoption of new drugs is heavily influenced by the extent to which their peers have adopted those new drugs.

 The more the United States can build experience with biosimilars, the more peer influence and clinical confidence will improve biosimilar uptake.

It is important to note that to develop more robust RWE with the goal of influencing clinical acceptance, a multi-stakeholder approach is necessary. As noted in the Cardinal Health study, 65% of survey respondents feel that the economics of biosimilars are not favorable enough to motivate them to switch from the reference product. Reimbursement, accessibility, support services, and other considerations all must align to enable provider adoption of biosimilars. With additional RA therapeutic biosimilars already FDA approved and “on deck” to come to market over the next few years (most notably in 2023 with the adalimumab biosimilars), provider confidence in both the clinical evidence and the payer and reimbursement landscape will be critical to the future success of biosimilars in the United States.

1. Kalkan A, Roback K, Hallert E, Carlsson P. Factors influencing rheumatologists’ prescription of biological treatment in rheumatoid arthritis: an interview study. 

2. Donohue JM, Guclu H, Gellad WF, et al. Influence of peer networks on physician adoption of new drugs. 

Cardinal Health Specialty Solutions has produced a Rheumatology Insights report that includes results from a survey of over 100 US-based rheumatologists on their perceptions and experiences with biosimilars in rheumatology thus far.

Sonia T. Oskouei, PharmD, BCMAS, DPLA

Opinion: Is the Ophthalmology Market Ready to Embrace Biosimilars?

US Rheumatologists Are Comfortable With Biosimilars, but Still Hesitant to Prescribe