AMD: Brolucizumab Noninferior to Aflibercept in Early Study

Jennifer Garcia

September 18, 2017

Brolucizumab has a comparable efficacy and safety profile to aflibercept among patients with neovascular age-related macular degeneration (AMD), results of a phase 2 study suggest. One expert not involved in the study cautions that the data are preliminary, and longer, large studies are needed to properly test the agent.

The authors, led by Pravin U. Dugel, MD, from Retinal Consultants of Arizona, in Phoenix, note that the experimental drug may reduce the lower treatment burden for patients. They report the results of their study in an article published in the September issue of Ophthalmology.

The researchers enrolled 89 treatment-naive patients with active choroidal neovascularization secondary to AMD. All patients were 50 years of age or older. The researchers randomly assigned patients in a 1:1 manner to receive either intravitreal brolucizumab (6 mg/50 μL) or aflibercept (2 mg/50 μL). Both groups were treated every 8 weeks for 40 weeks after 3 monthly loading doses. During weeks 40 through 56, the brolucizumab group switched to an every-12-week cycle, and the aflibercept group remained on an every-8-week cycle.

The primary endpoints were best corrected visual acuity change from baseline at weeks 12 and 16, based on a noninferiority margin of 5 letters at a 1-sided alpha level of 0.1.

The researchers found that patients in the brolucizumab group had similar best corrected visual acuity results at 12 weeks compared with the aflibercept group (5.75 vs 6.89 letters, respectively; 80% confidence interval [CI] for treatment difference, −4.19 to 1.93). Similar results were found at week 16 (6.04 vs 6.62 letters, respectively; 80% CI, −3.72 to 2.56 letters).

Further, the researchers found that patients in the brolucizumab group required six additional unscheduled treatments in five participants, whereas those in the aflibercept group required 15 treatments in 10 participants.

The adverse events reported between the two groups were similar, with no unexpected events.

The authors caution that treatment regimens for patients with AMD will still require an individualized approach, but they may be able to extend the treatment cycles for brolucizumab. "A 12-week treatment cycle for brolucizumab may be viable in a relevant proportion of eyes," they write.

The authors point out that these results have been used to design phase 3 studies that are currently underway ( identifiers: NCT02307682 and NCT024343).

Encouraging Results, but More Studies Needed

"This is a small phase 2 trial, and it shows promise, but that is all," wrote Abdhish Bhavsar, MD, clinical spokesperson for the American Academy of Ophthalmology, in an email interview with Medscape Medical News.

Dr Bhavsar expressed concern about the primary endpoints being assessed at weeks 12 and 16, noting that "[s]hort term results in smaller phase 2 trials have proven to be unreliable in predicting the outcomes of larger, well-designed phase 3 clinical trials."

"While this very short-term study shows promise in the treatment of neovascular AMD, we must await the results of the larger phase 3 clinical trial," concluded Dr Bhavsar.

Funding for this study was provided by Alcon Research, Ltd. All study authors have disclosed a financial relationship with Alcon. Dr Bhavsar has disclosed no relevant financial relationships.

Ophthalmology. 2017;124(9):1296-1304. Abstract

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