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Dr. Khanani highlights data from MERLIN showing noninferiority of brolucizumab to aflibercept in nAMD treatment, but a higher rate of intraocular inflammation.
Adverse events following treatment with brolucizumab of patients with neovascular age-related macular degeneration and persistent retinal fluid led to the discontinuation of the Phase 3a MERLIN trial, according to new data presented at the American Academy of Ophthalmology 2021 Meeting.
In an interview with HCPLive, presenting author, Arshad Khanani, MD, Managing Partner, Sierra Eye Associates, discussed the study meeting the primary endpoint of noninferiority of brolucizumab to aflibercept.
He noted that there was superiority of brolucizumab when looking at change from baseline to week 52, as well as patients who had more dry retina when treated with the agent. However, due to adverse events, it is not recommended to use brolucizumab more often than every 8 or 12 weeks following the loading dose.
“More ocular events of special interest the rate of inflammation in patients treated with Brolucizumab was 9.3%, compared to 4.5% in aflibercept,” Khanani said. “And that's why the second year of the MERLIN trial was discontinued.”
Khanani spoke on the expectation of the adverse events, explaining the prior knowledge of higher rates of intraocular events in brolucizumab treatment, compared to aflibercept. However, in the Phase 3 HAWK and HARRIER studies, the rate was 4%, compared to 9.3% in MERLIN.
“I think it has to do with the intensity and frequency of treatments,” he said. “In HAWK and HARRIER, patients received three monthly dosing and then Q8 and Q12 weeks. In this trial, we have patients who are treated with anti VEGF, and they're getting monthly continuous treatment of Brolucizumab.”
He then noted the goal of the study was to allow patients to control disease activity and stabilize anatomy so vision is not lost over time, as patients with persistent fluid, particularly intraretinal fluid, will lose vision over time.
“Keep in mind that this study was designed before we knew about the safety signals,” he said. “We knew about IOI rates, but there's also retinal vasculitis, retinal artery occlusion, those are the concerning events. We learned about that once Brolucizumab launched.”
Khanani spoke on data presented earlier this year about fluid in patients with a port delivery system, which showed the majority had no fluid and were well controlled. However, he noted that this is a different population of patients who have persistent fluid, despite receiving anti-VEGF injections.
“I think the port delivery system is really exciting to decrease the treatment burden for our patients as well as maintain anatomy,” Khanani said. “But, the question is, is this the right population where you have suboptimal responders to ranibizumab or aflibercept?
As a conclusion, Khanani summed up that brolucizumab cannot be given monthly and it is not for patients with persistent disease activity with vision loss.
“It is not for patients who are well controlled with current agents and and and the reason is the differences in safety,” he said. “Of course, anatomy is important, visual acuity is important, but if there's a safety concern or a signal that's different than obviously, we are going to use that as the last resort for our patients.”