18-Month Results of the FILLY Trial in Geographic Atrophy

The phase 2 FILLY trial found that APL-2 injections both monthly and every other month slowed lesion growth compared to sham.

An investigational complement C3 inhibitor, APL-2, shows promise in slowing the rate of growth of geographic atrophy lesions in the eye. The phase 2 FILLY trial found that injections both monthly and every other month slowed lesion growth at 12 months compared to sham. After injections ended at 12 months, treated patients continued to have less lesion growth compared to sham.

David Brown, MD, the director of research at Retina Consultants of Houston in Texas presented the 18-month results of the FILLY trial at the 2018 American Academy of Ophthalmology Annual Meeting in Chicago, IL.

“It’s really the most positive trial we’ve ever had in geographic atrophy,” Brown told MD Magazine® in an interview. “What it demonstrates is, in these patients that get the complement C3 inhibitor—for the first 6 months the growth rate is about the same as sham, but then from 6 months to 12 months, there’s a statistical and consistent slowing down of the process of that atrophy progression.”

The FILLY trial included 246 patients who were randomized to either APL-2 15 mg monthly (n = 86), APL-2 15 mg every other month (EOM) (n = 79), or sham (n = 81). Participants were treated over the course of 12 months and follow-up extended for 6 additional months after treatment stopped.

As previously reported, at 12 months, geographic atrophy growth slowed by 29% in the monthly APL-2 group (P = .008) and 20% in the EOM APL-2 group (P = .067) compared to sham.

After the cessation of treatment, the lesion growth resumed, but the treatment effects were maintained through 18 months. At 18 months, the lesion growth difference compared to sham was 16% for the EOM group (P = .097) and 20% for the monthly injection group (P = .044).

Unlike many trials conducted in patients with geographic atrophy, the FILLY trial did not exclude participants with neovascular age-related macular degeneration, also known as wet AMD, in the fellow eye.

“In the real world you get ticks and fleas. A lot of our patients have geographic atrophy and neovascularization,” said Brown during a presentation of 18-month data from the FILLY trial at the 2018 AAO Annual Meeting.

Treatment-related ocular adverse events occurred in the study eye of 22 (25.6%) of the monthly injection group, 11 (13.9%) of the EOM group, and in none of the sham group. Of note, endophthalmitis occurred in 2 (2.3%) participants in the monthly group and 1 (1.3%) participant in the EOM group, with no occurrence in the sham group.

The study also showed that there was an increase in exudation in the study eye, with patients with a history of choroidal neovascularization (CNV) in the fellow eye more likely to develop exudation in the study eye.

Among all patients, exudative AMD developed in 18 (20.9%) monthly participants, 7 (8.9%) EOM participants, and 1 (1.2%) sham participant. Among patients with a history of CNV, 13 of 36 (36.1%) in the monthly group, 5 of 28 (17.9%) in the EOM group, and none in the sham group developed exudative AMD. For those with no history of CNV in the fellow eye, exudative AMD developed in 5 of 50 (10.0%) and 2 of 51 (3.9%) in the monthly and EOM groups, respectively, and in 1 of 52 (1.9%) in the sham group.

Brown shared that a long-term phase 3 trial of APL-2 has just started, which will run for 2 years.