Ophthalmology Biosimilars May Face a Formidable Challenger

In researching an update on Oncobiologics, an organization that once had an interest in producing biosimilars (adalimumab and bevacizumab), I found a compelling issue that could seriously affect the likelihood of success for several other biosimilar manufacturers.

It turned out that Oncobiologics was rebranded Outlook Therapeutics in 2018. At the time, the newly rechristened company announced that it would no longer develop biosimilars for the US market. Although it dropped its interest in an Avastin® biosimilar, if successful, Outlook Therapeutics may undermine the expectations of ophthalmologic biosimilar makers.

Compounded Bevacizumab Still Number 1 for Wet Macular Degeneration

According to Outlook’s data, Avastin’s off-label use dominated the age-related wet macular degeneration market in 2016, at roughly half of the patient volume. In a 2018 survey of 740 US retinal specialists, off-label Avastin use for this disorder was even greater, at 70%. This off-label version must be compounded by a pharmacy to create the lower-dose solution required for intravitreal administration.

A study published in 2011 in the New England Journal of Medicine found that the compounded formulation of bevacizumab and the biologic ranibizumab (Lucentis®) were of equivalent efficacy for this indication. This makes sense, because ranibizumab and bevacizumab are derived from the same monoclonocal antibody; ranibizumab is a fragment of the full bevacizumab molecule. Another clinical trial found that compounded bevacizumab was as effective as aflibercept (Eylea®) in treating central retinal vein occlusion–associated macular edema. When compounding pharmacies created the ophthalmic formulation from a single vial of Avastin, the yield was dozens of doses, costing a fraction of that for Lucentis and Eylea. The only issue was whether the compounding pharmacies could ensure a contaminant-free product for patient use.

Outlook Therapeutics’ lead pipeline product is a manufactured ophthalmologic form of bevacizumab (ONS-5010). In commercializing a cGMP-produced ophthalmic formulation of bevacizumab, Outlook seeks to retain the drug’s value and efficacy while ensuring its safety. The drug maker is hoping to file a 351(a) biologic licensing application in the second half of 2021. A phase 3 trial was completed in August 2020 in which 61 Australian patients with choroidal neovascularization secondary to age-related macular degeneration were given either ranibizumab or ONS-5010. A larger phase 3 trial of 227 patients is set to wrap up in July 2021.   

Shrinking Market Expectations

This development may certainly affect the sales potential for the developing Lucentis and Eylea biosimilars marketplace. As covered last year, Lucentis’ sales are slipping, mostly due to competition with Eylea. Roche indicated an estimated annualized 2020 US sales of approximately $1.7 billion. Eylea’s 2020 annualized US sales may be about $4.8 billion, based on Regeneron’s third-quarter 2020 net sales figures. A corporate presentation by Outlook indicated that Eylea’s share is more than 30% of the wet macular degeneration market.

Assuming Outlook Therapeutics is successful in obtaining approval of its 351(a) application with the FDA, this could first occur in late 2022. The earliest any aflibercept biosimilar will come to the market will be around that same time. Two ranibizumab biosimilars may be ready for launch in 2021. If Outlook prices its new ophthalmologic formulation of bevacizumab at a solid discount to the aflibercept and ranibizumab biosimilars, payers would be justified in requiring the reference brands and biosimilars be stepped through ONS-5010. Such a prior authorization requirement or step edit, especially in the Medicare space, could significantly limit the projected revenues of ranibizumab and aflibercept biosimilars.

Since compounded bevacizumab is the dominant treatment in the age-related macular degeneration category, providers have already experienced ramifications on buy-and-bill practices relative to Eylea or Lucentis prescribing. After obtaining FDA approval, payers would need little incentive to utilize specialty pharmacies for product purchase and delivery of ONS-5010 to the physicians’ offices.

This rosy scenario for Outlook Therapeutics may not last, however. Investigational anti-VEGF treatments are being studied for their improved duration of action, requiring less-frequent intravitreal injections. This characteristic alone could make them more attractive than today’s options.

It is possible that developers of ranibizumab and aflibercept biosimilars are solely focused on their smaller reference targets with multibillion-dollar sales. Yet, the manufacturer of ONS-5010 may gain additional, significant marketshare at the expense of the biosimilar makers, if they play their cards right.

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