Faricimab Data in Wet AMD

Arshad Khanani, MD: In terms of the data we have on faricimab and neovascular AMD [age-related macular degeneration], we have 2 large phase 2 trials—especially AVENUE, a very large trial—which showed efficacy of faricimab given monthly or every other month where patients had good visual acuity gains. The safety was very comparable to ranibizumab. Then the SIERRA [-AMD] trial, where I was the lead author on that paper, we looked at patients receiving faricimab every 16 weeks and every 12 weeks. We know that patients with current treatment—let’s say ranibizumab, based on the EXCITE trial and other trials—they cannot sustain vision with quarterly dosing. When we designed STAIRWAY, we were looking at whether we can sustain visual acuity gains with every 12-week or every 16-week dosing compared to monthly ranibizumab. The STAIRWAY trial really showed the durability, where every 16-week and every 12-week dosing with faricimab was comparable, in terms of visual acuity as well as anatomy, to ranibizumab. That’s why we used that to design the phase 3 pivotal TENAYA and LUCERNE trials. The key thing about the trial design is that the patients receive faricimab. They receive 4 loading doses, and the reason that was done is that, based on prior data, we saw that patients continue to gain vision with faricimab with 4 loading doses. They receive 4 loading doses followed by disease activity at week 20 and week 24. Let’s say the patient gets treated, they’re in the faricimab group, these are all naïve patients that are in this trial. If they had disease activity at week 20, they were moved to the every 8-week treatment because they’re high-need patients. If they had disease activity at week 24, then they were put into the every 12-week treatment arm. But if they had no disease activity at week 24, they continued on and got into the every 16-week arm. One thing to keep in mind, there are no rescues in this trial. Patients, once they are in a swim lane, they stayed in the swim lane throughout the study. The other thing to keep in mind is the fact that the comparator here is different than in STAIRWAY. The comparator here actually is aflibercept, and the reason for that was, as I said, aflibercept is a better drying agent and the most utilized agent. Aflibercept was used for the label where patients receive 3-monthly dosing followed by every 2-month dosing based on the label. When I look at the data, this was a noninferiority trial design. Another thing to keep in mind—when you have good visual-acuity patients, like there were in TENAYA and LUCERNE, and it’s a noninferiority trial design that we are looking at—is whether patients have durability with faricimab, where faricimab patients are getting treated every 8 to up to 16 weeks. Can they do similar or better than aflibercept? Mean visual acuity was about 60 letters in TENAYA at baseline and about 58 to 59 in LUCERNE. I am mentioning that because we are used to seeing 9 to 11 letter gains in ANCHOR and MARINA and VIEW 1 and VIEW 2, but those patients were close to 50 to 55. The visual acuity gains that we’re getting here in TENAYA and LUCERNE are actually 5 to 7 letters, and that’s because patients are starting at better visual acuity.

What was noticed was that these studies met the primary end point of noninferiority, where the patient is treated with faricimab up to 16 weeks, were comparable to patients treated with aflibercept. Then the other thing to look at is obviously the CST [central subfield thickness] or the drying effect of faricimab compared with aflibercept. It appears to me that there is a trend where patients treated with faricimab actually appear to have dry retina and less fluctuations compared with aflibercept. Again, the majority of these patients are not treated q8 weeks. In terms of durability, 45% of patients in LUCERNE and TENAYA went q16 weeks. That’s every 4 months of treatment. I think that is significant in terms of decreasing the treatment burden, and if you look at patients going 12 weeks or longer, almost 80% of patients went 12 weeks or longer in TENAYA and LUCERNE while maintaining their visual acuity, similar to aflibercept, while maintaining their CST, which were similar to aflibercept, and again, patients treated with aflibercept were treated every 8 weeks. Of course, it’s a newer agent. We have large clinical trial data from the phase 2 program, but safety is crucial. The good news is the safety was comparable in faricimab. Compared with aflibercept there were no cases of retinal vasculitis or retinal artery occlusion in this trial, which is really reassuring that we have an agent that is more durable compared with aflibercept but also has comparable safety.

Transcript Edited for Clarity