This week, the FDA granted priority review to Novartis’ innovator biologic, RTH258, brolucizumab. The biologic is intended to treat wet age-related macular degeneration (AMD), or neovascular AMD. Novartis said in an announcement that, if the drug is approved, it could launch as soon as the end of 2019.

Brolucizumab is a humanized single-chain antibody fragment with enhanced tissue penetration and rapid clearance from systemic circulation. The structure results in a small molecule, 26 kDa, that allows for the inhibition of all isoforms of vascular endothelial growth factor (VEGF). Single-chain antibodies have been shown elsewhere to be suitable for high, less frequent doses that result in lower systemic exposure, which means that the treatment has the potential to reduce the burden of injections for patients.

The application for the new biologic is based on phase 3 data from 2 prospective, randomized, double-masked multicenter studies, both of which had noninferiority to fellow anti-VEGF agent aflibercept (Eylea) as a primary endpoint. The head-to-head trials demonstrated that the proposed biologic was effective at week 48 and was noninferior to aflibercept.

In terms of a secondary endpoint, brolucizumab outperformed aflibercept; in both studies, significantly fewer patients treated with brolucizumab had disease activity, as well as retinal fluid, versus patients treated with aflibercept.

Novartis’ filing for the anti-VEGF agent comes as biosimilars for anti-VEGF therapies are advancing; Republic of Korea-based Alteogen has recently secured a process patent for its aflibercept biosimilar, which it says has better resilience to high temperatures and a longer shelf-life than the innovator drug. Momenta and Mylan have entered a phase 3 pivotal trial of a biosimilar aflibercept candidate as of August 2018. Additionally, Coherus BioSciences is advancing an aflibercept candidate and a ranibizumab candidate, referencing the anti-VEGF agent Lucentis. Xbrane Biopharma and Samsung Bioepis are also both working on biosimilars of ranibizumab.

Finally, the FDA has approved a biosimilar bevacizumab (referencing Avastin), under the brand name Mvasi. While bevacizumab does not carry an indication for the treatment of eye disorders, it is routinely used off-label as an alternative to other, more expensive anti-VEGF agents in ophthalmology.  

It remains to be seen whether brolucizumab will be able to differentiate itself from a bevy of potentially cost-saving anti-VEFG biosimilars with its superiority in terms of retinal fluid and the benefit of less frequent injections. However, what is clear is that Regeneron, maker of the brand-name aflibercept, would feel significant pressure from both the market entry of biosimilars referencing its product and the launch of a novel competitor, particularly if Novartis chooses to launch its product at an attractive price.



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