On September 9, 2021, Apellis Pharmaceuticals, Inc. (the “Company” or “Apellis”) announced top-line data from its Phase 3 DERBY and OAKS clinical trials evaluating intravitreal pegcetacoplan in a total of 1,258 adults with geographic atrophy, or GA, secondary to age-related macular degeneration, or AMD.
DERBY (621 patients enrolled) and OAKS (637 patients enrolled) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of intravitreal pegcetacoplan with sham injections in patients with GA secondary to AMD. The primary objective of the studies is to evaluate the efficacy of pegcetacoplan in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence (p-value less than 0.05) at 12 months. Patients in DERBY and OAKS will continue on masked treatment for 24 months.
Monthly and every-other-month treatment with pegcetacoplan met the primary endpoint in OAKS, significantly reducing GA lesion growth by 22% (p=0.0003) and 16% (p=0.0052), respectively, compared to pooled sham at 12 months. DERBY did not meet the primary endpoint, showing a reduction in GA lesion growth of 12% (p=0.0528) and 11% (p=0.0750) with monthly and every-other-month treatment, respectively, compared to pooled sham at 12 months. In a prespecified analysis of the combined DERBY and OAKS studies, monthly and every-other-month treatment with pegcetacoplan reduced lesion growth by 17% (p<0.0001) and 14% (p=0.0012), respectively, compared to pooled sham at 12 months.
In a prespecified analysis of the primary endpoint, pegcetacoplan demonstrated a greater effect in patients with extrafoveal lesions at baseline. Patients with GA typically present first with extrafoveal lesions, which then progress toward the fovea where central vision is impacted. In the combined studies, monthly and every-other-month treatment with pegcetacoplan decreased GA lesion growth by 26% (p<0.0001) and 23% (p=0.0002), respectively, in patients with extrafoveal lesions, compared to pooled sham at 12 months.
In another prespecified analysis looking at the untreated fellow eye in patients with bilateral GA in the combined studies, monthly treatment with pegcetacoplan reduced lesion growth by 16% and every-other-month treatment with pegcetacoplan reduced lesion growth by 11%, in each case compared to the untreated fellow eye at month 12. In the sham group, the lesion in the study eye grew faster by 4% compared to the lesion in the fellow eye.
The Company also observed that the underlying lesion growth rate in the untreated fellow eye in the monthly pegcetacoplan groups was higher than the untreated fellow eye in the sham groups by 11% in DERBY and 7% in OAKS at month 12. In the every-other-month pegcetacoplan group, the lesion growth rate was higher by 1% in DERBY and 3% in OAKS as compared to the untreated fellow eye in the sham groups at month 12.
Pegcetacoplan was well tolerated in both Phase 3 studies. The pooled rate of new-onset exudations was 6.0% of patients in the monthly pegcetacoplan groups, 4.1% in the every-other-month pegcetacoplan groups, and 2.4% in the sham groups. Two cases of confirmed infectious endophthalmitis and one case of suspected infectious endophthalmitis were observed in the study eye out of a total of 6,331 injections (0.047%). Thirteen events of intraocular inflammation were observed in the studies (0.21% per injection). No events of retinal vasculitis or retinal vein occlusion were observed. There were no clinically relevant changes in vision for patients who developed infectious endophthalmitis or intraocular inflammation.
The Company believes that across the DERBY, OAKS and Phase 2 FILLY trials, pegcetacoplan has demonstrated an efficacy and safety profile with both monthly and every-other-month dosing that supports approval for the treatment of patients with GA. The Company plans to discuss these results with regulatory authorities worldwide. The Company expects to submit an NDA for approval in the United States in the first half of 2022. The Company also plans to submit a market authorization application for approval in Europe. The European Medicines Agency has recommended that the Company include 24-month functional data as part of that submission.
The Company plans to continue the buildout of its ophthalmology commercial and medical affairs team and has hired marketing and sales leadership in the United States and built out its European team and affiliates in Germany and Australia.
