Faricimab for Wet Age-Related Macular Degeneration

Arshad Khanani, MD: Looking at treatments in the pipeline, the most advanced program currently is faricimab, and luckily, we’ve been involved with faricimab since the early days when we participated in the initial trial. The faricimab program is really done well in terms of collecting and showing data. We recently had a readout of the phase 3 trials in both DME [diabetic macular edema] and neovascular AMD [age-related macular degeneration]. But before we talk about that, let’s talk about what faricimab is. Faricimab is a bispecific antibody. It’s the first bispecific antibody that is being utilized in ophthalmology to treat retinal diseases. It’s an intravitreal injection just like other injections we do. What it does is it blocks VEGF-A. It has two arms, since it’s a bispecific, and VEGF-A has been known to control disease. That’s what we do with ranibizumab, aflibercept, bevacizumab, and brolucizumab. It blocks VEGF-A, but another thing it does is block ANG2 [angiopoietin-2]. There has been a lot of preclinical work, as well as early clinical work, showing the benefit of blocking ANG2. ANG2 is a soluble ligand that gets up-regulated in retinal vascular diseases.

If you look at patients with neovascular AMD, at patients with diabetic retinopathy, at patients with retinal vein occlusion, we have data showing that levels of ANG2 are elevated. In normal quiescent vessels, levels of ANG2 are low, but the levels of ANG1 are activated, the type II receptor is phosphorylated and active, and the vasculatures are stable. There is no leakage, there is no inflammation. The parasites are not lost. When ANG2 goes up, it leads to leakage, it leads to breakdown of the trijunction, it leads to parasite loss leading to inflammation, and fibrosis, based on the preclinical work. It’s exciting that we now have a single injection—basically 1 molecule with 2 targets—to address retinal vascular diseases.

Transcript Edited for Clarity