Avacincaptad Pegol Slows Progression of Geographic Atrophy

Intravitreal injections of avacincaptad pegol (ACP) (2mg and 4mg), a complement C5 inhibitor, slows the progression of geographic atrophy (GA) relative to sham for 1 year, according to research presented at the American Academy of Optometry 2022 annual meeting, held in San Diego, CA, from October 26 to October 29, 2022. The research also shows the treatment is well tolerated.

Currently, no approved treatments for preventing or slowing the progression of GA exist, according to Mohammad Rafieetary, OD, who presented on the trial at the conference. In the GATHER1 and GATHER2 trials, the efficacy and safety of ACP in slowing the progression of GA was evaluated. 

GATHER1 was a randomized, double-masked, sham-controlled, 18-month, phase 2/3 trial that evaluated the efficacy and safety of monthly intravitreal injections of ACP in participants with GA. Participants in GATHER1 were randomly assigned 1:1:1 to ACP 1 mg, ACP 2 mg, or sham (part 1) or 1:2:2 to ACP 2 mg, ACP 4 mg, or sham (part 2).

GATHER2 is currently an ongoing randomized, double-masked, sham-controlled, 24-month, phase 3 trial assessing monthly and every-other-month intravitreal injections of ACP 2 mg in participants with GA. Participants in GATHER2 were randomly assigned 1:1 to ACP 2 mg monthly or sham. At month 12, the participants were re-randomly assigned to ACP 2 mg monthly or ACP 2mg every other month.

In both studies, participants were 50 years of age or older with GA inside or outside of the 1.5 mm-diameter foveal area.

GATHER1 included a total of 286 participants. The least squares average change from baseline to month 12 in GA lesion area (square root transformation) was 0.292 mm for participants receiving ACP 2 mg and 0.402 mm for the corresponding sham group, which translated into a 27.4% decrease in the average GA growth rate with ACP 2 mg (P =.0072). The least squares average change from baseline to month 12 in GA lesion area was 0.321 mm for participants receiving ACP 4 mg and 0.444 mm for the corresponding sham group, which was a 27.8% decrease in the average GA growth rate with ACP 4 mg (P =.0051). 

During the 18 months of GATHER1, 1 or more ocular treatment-emergent adverse event (TEAE) in the study eye was noted in 63.6% of participants in the combined ACP groups as well as 40.9% of participants in the combined sham groups. The majority of the most frequent TEAEs were related to the injection procedure, according to the report. 

“The topline 12-month efficacy and safety results of the GATHER2 study will be presented,” according to the research. “The complement C5 inhibitor ACP (2 mg and 4 mg) was found to slow the progression of GA relative to sham over 12 months and was tolerated in the GATHER1 trial.”