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Charles Clifton Wykoff, Federico Grossi; APL-2, a Complement C3 Inhibitor, Slows the Growth of Geographic Atrophy Secondary to AMD: 18-month Results of a Phase 2 Trial (FILLY). Invest. Ophthalmol. Vis. Sci. 2018;59(9):72.
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To evaluate the safety and efficacy of APL-2 (pegcetacoplan, 15mg), a complement C3 inhibitor, administered intravitreally for 12 months, with follow-up for an additional 6 months, in subjects with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Patients with GA area measuring 2.5-17.5 mm2 and best-corrected visual acuity (BCVA) of 24 letters or better (20/320 Snellen equivalent) were eligible. There were no exclusions based on fellow eye disease state. Subjects were randomized (2:2:1:1) to four arms; APL-2 monthly, APL-2 every other month (EOM), sham monthly, & sham EOM. Total treatment period was 12 months with additional assessments at 15 & 18 months. The 12-month primary efficacy outcome was the difference in mean change from baseline of the square-root GA area based on fundus autofluorescence. Secondary endpoints included change in BCVA & incidence of conversion to exudative AMD.
Among the 246 randomized patients, treatment groups were well balanced with respect to demographics, GA area, GA bilaterality, & history of fellow eye exudative AMD. The primary outcome was assessed using a pre-specified modified intent-to-treat population (mITT; N=243). At 12 months, monthly APL-2 (N=84) slowed GA growth by 29% (p=0.008) and EOM APL-2 (N=78) slowed GA growth by 20% (p=0.067) versus the pooled sham group (N=80). The effect increased in the second six months of treatment, during which monthly & EOM APL-2 slowed GA growth by 47% (p<0.001) & 33% (p=0.01) respectively vs sham. No differences in BCVA outcomes were observed between treatment & sham groups. There was a dose-dependent difference in onset of investigator-determined study eye conversion to exudative AMD: 15 eyes in monthly APL-2, 6 eyes in EOM APL-2, & one eye in sham. These eyes discontinued active APL-2 treatment at the time of conversion to exudative AMD and overall visual and anatomic outcomes were not negatively impacted. Most other adverse events were attributable to the intravitreal injection procedure.
At 12 months, intravitreal APL-2 slowed GA growth and this treatment effect was more pronounced in the second six months of therapy. APL-2 was associated with an increase in study eye conversion to exudative AMD, though overall visual and anatomic outcomes were not negatively impacted.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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