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Results of two national multicenter prospective randomized clinical trials show that the drug brolucizumab (Novartis) delivers a superior retinal drying effect compared with aflibercept (Eylea, Regeneron Pharmaceuticals) for patients with neovascular age-related macular degeneration (nAMD).
“The ability to dry the retina is an important outcome,” says Rishi P. Singh, MD, retina specialist at Cole Eye Institute, who presented results of the HAWK and HARRIER trials at the Association for Research in Vision and Ophthalmology annual meeting. “These studies found that brolucizumab dries the retina better than we see with any other drugs that are currently on the market.”
The two 96-week studies also found that brolucizumab has a greater durability of action, crucial for patients who struggle to adhere to once-a-month or every-other-month injection regimens due to health or travel, Dr. Singh says.
“This helps us keep their disease under control for longer times between appointments,” he explains.
HAWK and HARRIER
In the HAWK study, patients were randomly assigned to receive 3 or 6 mg doses of brolucizumab or 2 mg of aflibercept. In HARRIER, they were randomly assigned to 6 mg of brolucizumab or 2 mg of aflibercept.
In the loading phase of the studies, all treatments were given monthly (Weeks 0, 4 and 8) with no treatment given at Week 12. Next, the brolucizumab patients received an injection every 12 weeks, with an option of dosing every eight weeks for patients who showed signs of disease activity as determined by masked investigators. Aflibercept patients received a dose every eight weeks, as per the labeling.
Brolucizumab achieved superior reductions in central subfield thickness (CST) from baseline to Week 16 and Week 48, and the difference was maintained at Week 96. More patients achieved fluid resolution with brolucizumab during both the matched and maintenance phases up to Week 96, and more patients demonstrated sustained dryness for ≥ two and ≥ three consecutive visits to Week 96 with brolucizumab.
Importantly, more than three-quarters of the patients who were given 6 mg of brolucizumab who completed Week 48 on every-12-week dosing were able to remain on that schedule through the studies’ completion at Week 96 (82% in HAWK and 75% on HARRIER). These numbers are consistent with those seen at Week 16, when just 24% of patients receiving 6 mg of brolucizumab showed disease activity in HAWK (compared with 34% of aflibercept patients) and 22.7% in HARRIER (compared with 32.2% for aflibercept). Not only was this seen within the HAWK and HARRIER studies but also replicated in the OSPREY phase 2 study of brolucizumab versus aflibercept which he presented at the ARVO meeting further validating the results.
Brolucizumab, which was found to have an overall safety profile comparable to that of aflibercept, is not available commercially yet, but it is widely expected to launch early next year. Dr. Singh says he believes it will become an important part of retina specialists’ armamentarium of drugs for nAMD.
“We are very lucky to have a number of drugs to pick from to help our patients and we now look forward to having our patients on current therapy who have persistent fluid receive this new drug when approved,” he says. “They are all quite effective at helping us manage this condition.”
Real world applications TBD
He stresses that while the ophthalmic community has high hopes for brolucizumab based on clinical trials, real-world results can be very different.
“Patients don’t necessarily have the same disease they would have in a clinical study, so we will need to monitor outcomes carefully once the drug is available,” he says. “It will be interesting to see how patients do over the course of their treatments.”
While any patient with nAMD is a potential candidate for brolucizumab, Dr. Singh says that those who have logistical issues that make less-frequent dosing appealing are particularly good candidates. He says the drug is expected to cost in the same range as other drugs that are currently available.