New Anti-VEGF Agent, Brolucizumab, Cleared by FDA to Treat AMD

Even as biosimilars of anti—vascular endothelial growth factor (anti-VEGF) agents are coming to market and advancing through the pipeline, a new agent that may have substantial benefits for patients with wet age-related macular degeneration (AMD) has been approved by the FDA: brolucizumab, which sponsor Novartis will sell as Beovu.

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), and that makes the product suitable to deliver high concentrations of the drug.

As such, brolucizumab can be dosed once every 3 months, after a 3-month loading phase, without compromising its efficacy. In fact, in the 2 phase 3 clinical trials on which the product’s approval was based, HAWK and HARRIER, the new anti-VEGF agent was noninferior to fellow anti-VEGF therapy aflibercept (Eylea) at 1 year, despite longer treatment intervals for brolucizumab.

Brolucizumab also resulted in greater reductions in central subfield thickness, an indicator of retinal fluid, at week 16 and at 1 year, versus aflibercept. Both of the anti-VEGF agents had similar safety.

“Beovu is the first to offer less frequent dosing in the first year of therapy while maintaining its effectiveness. This gives more time for wet AMD patients to focus on what’s important in their lives,” said Marie-France Tschudin, president of Novartis Pharmaceuticals, in a statement.

Currently, aflibercept, which is targeted by biosimilar developers including Coherus BioSciences and the Momenta—Mylan partnership, is approved for dosing every 8 weeks or every 4 weeks. In 2018, the FDA also approved an updated label for a modified 12-week dosing schedule. Ranibizumab (Lucentis), targeted by biosimilar developers including Samsung Bioepis, is dosed every 1 month.

While less frequent intravitreal administration of anti-VEGF therapy is likely be a boon for patients, it remains to be seen whether such a benefit will help the newly approved product to overcome the appeal of bevacizumab and its biosimliars.

Bevacizumab, which does not have approved indications for eye disorders, has been shown to be noninferior to aflibercept in terms of visual acuity, and has become a widely used treatment option in lower-resource contexts. The off-label use of the agent has been upheld in the EU Court of Justice, and a recent study from Brazil demonstrated that using bevacizumab left over from oncology applications allowed 96.54% more patients to be treated for eye diseases.

Interest in an ophthalmologic indication for bevacizumab appears to be rising as well; during comments given a recent biosimilars congress, Steinar Madsen, MD, director of the Norwegian Medicines Agency, said that when a drug like bevacizumab sees its patents expire, “It should be taken over by authorities so academic research can result in new indications” that biosimilar developers can then use for their products. Bevacizumab, he said, could be granted indications for eye disorders based on the accumulated evidence available in the scientific literature to date. “That is one of the changes we should have in Europe,” he said.