Apellis announces 24-month results from Phase 3 DERBY and OAKS studies in GA

Apellis Pharmaceuticals Inc. today announced top-line data at 24 months showing increased effects over time with intravitreal pegcetacoplan, an investigational, targeted C3 therapy, in the Phase 3 DERBY and OAKS studies in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

The company noted in a news release that pegcetacoplan has the potential to become the first-ever treatment for GA, which is a leading cause of blindness.

Eleonora Lad, MD, PhD, lead principal investigator for the OAKS study, associate professor of ophthalmology, director of ophthalmology clinical research unit at Duke University Medical Center, noted in a news release that she was pleased to see the increased effects over time, which suggest that pegcetacoplan is preserving more and more photoreceptor cells that are directly responsible for vision.

“The vision loss caused by GA is devastating for patients, taking away their ability to perform critical daily tasks like driving, reading, and recognizing faces. It is very exciting to finally be on the brink of the first potential GA treatment with pegcetacoplan,” she said in the news release.

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

According to the news release, between months 18 and 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 news release noted that 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.

The company noted that the study found that consistant with expectations, investigators observed no meaningful difference between pegcetacoplan and sham in the key secondary endpoints measuring visual function at 24 months.

Moreover, the news release noted that studies show that GA lesion growth is correlated with loss of visual function over longer periods of time.¹ 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 extension study for an additional 3 years.

"These data further reinforce the breakthrough potential of pegcetacoplan, with both monthly and every-other-month treatment demonstrating increased effects across a broad patient population over 24 months,” said Jeffrey Eisele, PhD, chief development officer, Apellis. “With a U.S. PDUFA date in November and an EU submission planned later this year, we are committed to bringing pegcetacoplan to patients as quickly as possible.”

According to the press release, 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.^2,3,4

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.

The results at 24 months will be included in the marketing authorization application that the company plans to submit to the European Medicines Agency by the end of this year. The U.S. marketing application is under Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of Nov. 26, 2022.

References

1. Sunness JS et al. Ophthalmology. 1999;106:1768–79.

2. Morioka et al. Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics. Scientific Reports 2022

3. Kiss et al. Endophthalmitis rates among patients receiving intravitreal anti-VEGF injections: a USA claims analysis. Clin Ophthalmol 2018.

4. Cox et al. Inflammatory complications of intravitreal anti-VEGF injections. Journal of Clinical Medicine 2021.

5. Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta analysis. Ophthalmology 2012;119:571–580.

6. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116.

7. Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.
8Seddon, JM, Rosner, B. Validated prediction models for macular degeneration progression and predictors of visual acuity loss identify high-risk individuals. Am J Ophthalmol 2019;198:223–261.