On August 24, 2022, Apellis Pharmaceuticals, Inc. (the “Company” or “Apellis”) announced top-line data at 24 months showing increased effects over time with intravitreal pegcetacoplan in its Phase 3 DERBY and OAKS clinical trials in geographic atrophy (“GA”) secondary to age-related macular degeneration.
In a pre-specified analysis of GA lesion growth over 24 months, both monthly and every-other-month (“EOM”) pegcetacoplan showed a clinically meaningful reduction in GA lesion growth from baseline compared to sham (all p-values are nominal):
| | • | | DERBY: 19% monthly, p=0.0004; 16% EOM, p=0.0030 |
| | • | | OAKS: 22% monthly, p<0.0001; 18% EOM, p=0.0002 |
Between months 18-24, the pegcetacoplan treatment effect accelerated compared to previous six-month periods, with robust reductions of GA lesion growth versus sham (all p-values are nominal). The increased effects were driven by a greater slowing of lesion growth by pegcetacoplan and not by an increase in the lesion growth rate in the sham group, which was highly consistent over each of the four six-month intervals (1.0+/-0.05 mm2).
| | • | | DERBY: 36% monthly, p<0.0001; 29% EOM, p=0.0002 |
| | • | | OAKS: 24% monthly, p=0.0080; 25% EOM, p=0.0007 |
Additionally, the reduction of GA lesion growth in patients with extrafoveal lesions (28% monthly; 28% EOM) was comparable to the reduction in patients with foveal lesions (34% monthly; 28% EOM) in the combined studies between months 18-24.
During the six-month period between months 18-24, the treatment effect of pegcetacoplan in the pooled data increased compared to previous six-month periods, with reductions of GA lesion growth of 30% and 24% in the monthly and every-other-month arms, respectively, with nominal p-values < 0.0001 in both arms, when compared against pooled sham. Due to the statistical model used to analyze combined patient-level data, the treatment effect in the pooled data is not a simple average of the DERBY and OAKS results.
The nominal p-values presented above were calculated using the same methodologies as the month 12 and 18 analyses.
Consistent with expectations, no clinically meaningful difference was observed between pegcetacoplan and sham in the key secondary outcomes measuring visual function at 24 months. Studies show that GA lesion growth is correlated with loss of visual function over longer periods of time. The visual function outcomes at 24 months are believed to be due to the limitations of the endpoints when used for GA and the relatively early assessment timeframe. Patients will be treated with pegcetacoplan in the GALE open label extension study for an additional three years. All patients who completed the DERBY or OAKS studies were invited to participate in the GALE study. The objective of the GALE study is to evaluate the long-term incidence and severity of ocular and system treatment emergent adverse events as well as change in the total area of GA lesions as measured by fundus autofluorescence.
Pegcetacoplan continued to demonstrate a favorable safety profile, consistent with safety data to date and longer-term exposure to intravitreal injections. No cases of endophthalmitis were reported between months 18 and 24. Over 24 months, the rate of infectious endophthalmitis was 0.034% per injection and the rate of intraocular inflammation was 0.24% per injection, which continue to be generally in line with reported rates in studies of other intravitreal therapies. No events of occlusive vasculitis or retinitis were observed over 24 months, and no serious adverse events of ischemic optic neuropathy were reported between months 18 and 24. The combined rate of new-onset exudations at month 24 was 11.9%, 6.7%, and 3.1% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively.
