Brolucizumab as Good as Aflibercept for Neovascular AMD

By Will Boggs MD

June 04, 2019

NEW YORK (Reuters Health) - Brolucizumab is noninferior to aflibercept and requires less-frequent injections for patients with neovascular age-related macular degeneration (nAMD), according to results from two phase-3 trials.

"Brolucizumab has the potential to treat our patients in a more sustainable and effective fashion," Dr. Pravin U. Dugel from Retinal Consultants of Arizona, in Phoenix, and the University of Southern California's Roski Eye Institute, in Los Angeles, told Reuters Health by email.

Earlier this month, Novartis announced that the U.S. Food and Drug Administration accepted the company's brolucizumab application for the treatment of nAMD. The filing was based on data from the two trials, called HAWK and HARRIER, in which more than 1,800 patients at 408 sites around the world were randomized to receive brolucizumab or aflibercept (Eylea, Regeneron Pharmaceuticals).

After injections at weeks 0, 4 and 8 (loading phase), patients on brolucizumab received injections every 12 weeks unless disease activity was identified, at which time dosing was permanently adjusted to every eight weeks. Patients on aflibercept received injections every eight weeks.

About half of brolucizumab-treated eyes (49.4% with 3 mg and 55.6% with 6 mg in HAWK and 51.0% with 6 mg in HARRIER) were maintained on every 12 week dosing after loading through week 48.

The primary endpoint, mean change in best-corrected visual acuity (BCVA) from baseline to week 48, was similar for brolucizumab 3 mg and 6 mg and for aflibercept in both HAWK and HARRIER. Improvements ranged from 6.1 to 6.9 letters gained with brolucizumab and from 6.8 to 7.6 letters gained with aflibercept, differences that were within the noninferiority criteria.

Reductions in central subfield thickness (CST) on optical coherence tomography (OCT) from baseline to week 16 and to week 48 were significantly greater with brolucizumab than with aflibercept in both trials. And fewer brolucizumab-treated eyes than aflibercept-treated eyes in both studies had intraretinal fluid or subretinal fluid during follow-up, the researchers report in Ophthalmology, online April 12.

"The anatomic superiority of brolucizumab is the most important finding," Dr. Dugel said. "We treat based on the OCT, as this is the most objective biomarker we have available. The fact that brolucizumab has consistently shown anatomic superiority in 3 studies (HAWK, HARRIER and OSPREY) is impactful."

Overall ocular and nonocular adverse event rates were similar with brolucizumab and aflibercept in both trials.

"Brolucizumab gives us a better drug to treat a validated target," Dr. Dugel concluded. "We will be using this drug for treatment-naive patients as well as patients who have responded inadequately to our current drugs."

In email to Reuters Health, a spokesperson for Regeneron said Eylea has "set a high bar for many retinal disease treatments, with every 4-, 8- and 12-week dosing regimens approved for wet AMD per the label. For many people with wet AMD, what matters is maintaining their vision or regaining vision lost to the disease. To date, we have not seen any pivotal clinical data showing that any other therapy can improve visual acuity better than Eylea in wet AMD."

Novartis Pharma AG funded the studies, employed two authors and had various relationships with six others. Dr. Dugel reported no conflicts of interest.

SOURCE: https://bit.ly/2GuRVOY

Ophthalmology 2019.

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