Apellis unveils 18-month results from phase 3 OAKS and DERBY studies

According to the company, pegcetacoplan demonstrated continuous and clinically meaningful effects at month 18 in the studies, which also found that treatment effects in DERBY were comparable to OAKS during months 6 to 18. The combined 18-month data show the potential for improving treatment effects over time.

Apellis Pharmaceuticals Inc. today announced longer-term data from the Phase 3 DERBY and OAKS studies, which showed that intravitreal pegcetacoplan, an investigational, targeted C3 therapy, continued to reduce geographic atrophy (GA) lesion growth and demonstrate a favorable safety profile at month 18 for the treatment of GA secondary to age-related macular degeneration (AMD).

According to the company, these data will be included in the New Drug Application (NDA) that the company plans to submit to the US Food and Drug Administration (FDA) in the second quarter of 2022.

Jeffrey S. Heier, MD, principal investigator of the DERBY study and director, retina service and director, retinal research, Ophthalmic Consultants of Boston, noted in a news release that it was exciting to see these positive data with pegcetacoplan, which demonstrated continuous and potentially improving effects over time.

“These 18-month results provide further evidence that pegcetacoplan meaningfully slows disease progression and has the potential to preserve vision longer,” Heier said in a statement. “In my practice, I have seen how devastating it can be for people living with GA to lose more of their vision year after year. There is an urgent unmet need in GA, and these results reinforce the potential of pegcetacoplan to become the first-ever treatment for patients with this debilitating disease.”

In a longer-term analysis of the primary endpoint, pegcetacoplan continued to reduce GA lesion growth compared to pooled sham at month 18 (all p values are nominal):

  • In OAKS, pegcetacoplan reduced GA lesion growth with both monthly (22%; p<0.0001) and every-other-month treatment (16%; p=0.0018).
  • In DERBY, pegcetacoplan reduced GA lesion growth with both monthly (13%; p=0.0254) and every-other-month treatment (12%; p=0.0332).
  • Pegcetacoplan demonstrated marked improvements in DERBY during months 6-12 with reductions of 17% with monthly and 16% with every-other-month treatment compared to months 0-6, and the treatment effects were sustained through month 18. The treatment effects observed in DERBY were comparable with OAKS during months 6-18.
  • Data at 18 months from the combined studies show the potential for improving treatment effects with pegcetacoplan over time. The reduction in GA lesion growth improved with monthly pegcetacoplan treatment from 13% to 21% from months 0-6 to months 12-18. The reduction in GA lesion growth improved with every-other-month pegcetacoplan treatment from 12% to 17% from months 0-6 to months 12-18.

Federico Grossi, MD, PhD, chief medical officer at Apellis, noted in the news relese that pegcetacoplan is the only therapy to continuously reduce GA lesion growth across a large and broad patient population in Phase 3 studies.

“Building on our 12-month results, both monthly and every-other-month pegcetacoplan demonstrated clinically meaningful effects and a favorable safety profile with longer-term use,” Grossi said in a statement. “We look forward to submitting these data to the FDA and working with regulatory agencies to bring pegcetacoplan to people living with GA around the world as quickly as possible.”

According to Apellis, at month 18, pegcetacoplan continued to demonstrate a favorable safety profile, consistent with safety at 12 months and longer-term exposure to intravitreal injections. The rate of infectious endophthalmitis was 0.044% per injection, and the rate of intraocular inflammation was 0.23% per injection. Rates of endophthalmitis and intraocular inflammation continue to be generally in line with those reported in studies of other intravitreal therapies.1,2,3

No events of retinal vasculitis or retinal vein occlusion were observed. The combined rate of new-onset exudations at month 18 was 9.3%, 6.2, and 2.9% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively.

The company announced that it will present detailed data at an upcoming scientific meeting.

References
1. Morioka et al. Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics. Scientific Reports 2020.
2. Kiss et al. Endophthalmitis rates among patients receiving intravitreal anti-VEGF injections: a USA claims analysis. Clin Ophthalmol 2018.
3. Cox et al. Inflammatory complications of intravitreal anti-VEGF injections. Journal of Clinical Medicine 2021.