Is a better anti-VEGF molecule on the horizon for neovascular AMD?

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Despite several different therapies currently in use for the treatment of nAMD, multiple pathways are currently being evaluated to improve treatment options, according to a presentation by Dr Singh at Hawaiian Eye and Retina 2021.

Anti-VEGF is most often used to treat patients with nAMD and does so quite well, said Dr Sing, who said there has been a 72% reduction in the rate of legal blindness in the United States during over the course of the ant-VEGF area. Current anti-VEGF treatments for nAMD include bevacizumab (Avastin), aflibercept (Eylea), ranibizumab (Lucentis), and brolucizumab (Beovu).

“We are doing a great job but there are certainly areas we can improve upon,” said Dr Singh, noting high treatment burden, vision loss, and addressing only 1 mechanism of action as current issues.

One strategy for addressing these problems is building a better anti-VEGF molecule. Dr Singh highlighted several therapies that are currently being investigated including GB-102 (Graybug Vision Inc), abicipar (Allergan), KSI-301 (Kodiak), conbercept (Chengdu Kanghong Biotech), and aflbercept high dose (8 mg).

Preliminary topline results from the ALTISSIMO trial evaluating GB-102 compared to a single control arm of patients on aflibercept showed that the mean change from baseline for BCVA for all patients was about 9 letters lower across all time points than the control group.

In the CEDAR and SEQUOIA Phase 3 clinical trials comparing abicipar with ranibizumab, abicipar extended dosing intervals and resulted in a “significant improvement in vision compared to what was seen with ranibizumab in the treatment arm,” said Dr Singh. However, concerns over higher rates of interocular inflammation were noted.

Preclinical data on KSI-301 show promising improvement in bioavailability and durability has been reported and a phase 1b open-label study is currently underway to investigate further.  

Conbercept was approved by the Chinese Food and Drug Administration for the treatment of exudative AMD but after not meeting its primary endpoint in the PANDA trials, the “pathway forward is a concern,” said Dr Singh.

The current dose for aflbercept is 2 mg. A higher dose—8 mg—is currently being evaluated in the Phase 2 Candela and Phase 3 Pulsar/Photon trials.

Singh RP. Emerging Therapies for Neovascular AMD. Presented at: Hawaiian Eye and Retina 2021.

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