Charles Clifton Wykoff
With more than one million people affected by sight-threatening geographic atrophy secondary to age-related macular degeneration in the US alone, the need for a useful treatment is urgent. One-year results of a clinical trial with a novel complement C3 inhibitor suggest potential for this treatment approach, according to a report at the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting, in Honolulu, Hawaii.
Charles Clifton Wykoff MD, PhD, Retina Consultants of Houston, Blanton Eye Institute, Houston, Texas, US, presented the latest results from the FILLY trial, a multi-centre phase II placebo controlled randomised clinical trial. The 18-month trial looked at the safety and efficacy of a complement C3 inhibitor, APL-2 (pegcetacoplan, Apellis Pharmaceuticals), in 246 patients with geographic atrophy secondary to age-related macular degeneration (AMD).
Inclusion criteria included geographic atrophy measuring from 2.5 to 17.5mm2 and visual acuity of at least 20/320. Patients received one of three regimens, monthly intravitreal injections of APL-2, APL-2 injections every other month, placebo injections monthly or placebo every other month.
The study met its 12-month primary efficacy outcome, which was the difference in mean change from baseline of the square-root geographic area based on fundus autofluorescence. Monthly injection of APL-2 was associated with a statistically significant 29% reduction in the rate of geographic atrophy lesion growth. Patients treated with the active compound every other month showed a 20% slowing in lesion growth. These effects continued to increase through the 12-month study period. Patients on active treatment did not show any improvement in best-corrected visual acuity.
One unexpected finding was a dose-dependent difference in study eye conversion to the exudative form of AMD. Eighteen eyes (21%) receiving monthly injections converted to exudative AMD, as did seven eyes (9%) in the group treated every other month, along with one eye (1.2%) treated with sham injections. Active treatment was discontinued in all of those patients.
Subsequent analysis showed that patients who had a history or presence of choroidal neovascularisation in the other, non-study eye had a higher rate of conversion to the exudative form of the disease, with those receiving monthly treatment having the highest rate.
During a six-month follow-up period without active treatment, geographic atrophy lesions grew at a rate similar to that observed in placebo recipients. Patients previously treated with monthly APL-2 showed a slightly greater reduction over the six-month follow-up, 12% reduction compared to placebo. Those who had received treatment every other month showed a 9% reduction.
A phase III protocol for APL-2 for the treatment of geographic atrophy is scheduled to begin later this year (2018).
Charles Clifton Wykoff: ccwmd@houstonretina.com
