Apellis Announces 18-Month Data from Phase 1b Study of Pegcetacoplan in Patients with Geographic Atrophy (GA)
October 19, 2020
- First data for 18 months of treatment with intravitreal pegcetacoplan demonstrates continued slowing of GA lesion growth beyond 12 months
- Post hoc analysis demonstrated a 52% decrease in mean lesion growth in seven patients with bilateral GA comparing treated eye vs. untreated fellow eye at 18 months (p=0.01)
- Top-line data from Phase 3 DERBY and OAKS studies expected in Q3 2021
WALTHAM, Mass., Oct. 19, 2020 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in targeted C3 therapies, today announced 18-month data from the Phase 1b APL2-103 study of pegcetacoplan (APL-2) in patients with advanced geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and low vision. GA is a complement-driven eye disease1,2 that can cause blindness, affects approximately five million people globally3,4 and has no approved treatment. The study, which enrolled 12 patients with bilateral GA (disease in both eyes), was initiated to assess the safety of the Phase 3 formulation of pegcetacoplan (15mg/0.1mL).
Patients were dosed monthly with pegcetacoplan in one eye using the fellow eye as an untreated control. Apellis previously reported results at Month 12 in nine patients demonstrating a trend in reduced GA lesion growth in treated eyes versus untreated fellow eyes. The current post hoc analysis reports on the seven Phase 1b study patients for whom data were available for at least 18 months. In this population, the growth rate of GA lesions in the treated eye was on average 52% (mean square root) slower than the opposite untreated eye (p=0.01). It has been shown that lesions in both eyes tend to grow at the same rate in patients with bilateral GA.5 Of the 12 enrolled patients, there were no reported cases of inflammation and, as previously reported, one patient (8%) developed new-onset exudation at Month 12.
“It is exciting to see data for the efficacy of intravitreal pegcetacoplan at 18 months among patients with GA,” said Charles Wykoff, M.D., Ph.D., Director of Research, Retina Consultants of Houston, and Investigator of Apellis’ Phase 1b and Phase 3 GA trials. “These data align with the Phase 2 FILLY results, where patients with bilateral GA in the monthly treated population had a significant reduction in growth relative to their untreated fellow eye in a post hoc analysis at 12 months. Finally, while this is a limited number of patients, I am encouraged to see that the benefit of pegcetacoplan in slowing GA growth seems to be maintained through Month 18. I believe that a 52% reduction in GA lesion growth at Month 18 is likely to be highly clinically meaningful.”
Post hoc analysis at 18 months
Figure 1. Mean (± SE) change from baseline in square root GA lesion measured by fundus autofluorescence in the study eye (SE) and fellow eye (FE). Percentage difference and p value represents the comparison in GA growth between the study and fellow eye at each timepoint.
The ongoing pegcetacoplan development program in GA includes the Phase 1b APL2-103 study and the Phase 3 DERBY and OAKS studies. The patient population enrolled in the Phase 1b study is similar to DERBY and OAKS but allowed for more advanced disease with a wider range of baseline lesion size and lower baseline visual acuity.
The DERBY and OAKS studies were initiated in 2019 with the pegcetacoplan formulation tested in this Phase 1b study and top-line data are expected in the third quarter of 2021.
About the APL2-103 study
The APL2-103 study is a 12-patient Phase 1b, multicenter, open label, single arm, 24-month clinical trial to assess the safety of monthly intravitreal (IVT) injections of pegcetacoplan in patients diagnosed with advanced geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The primary outcome measures include incidence and severity of ocular and systemic treatment-emergent adverse events (TEAEs).
About the FILLY study
The FILLY study was a 246-patient, Phase 2, multicenter, randomized, single-masked, sham-controlled clinical trial evaluating pegcetacoplan in patients with GA secondary to AMD conducted at over 40 clinical sites in the United States, Australia and New Zealand. Pegcetacoplan was administered as an intravitreal injection monthly or every other month (EOM) for 12 months, followed by six months of monitoring after the end of treatment. The primary efficacy endpoint was the change in GA lesion area from baseline to Month 12 in pegcetacoplan-treated patients compared to sham.
About the DERBY and OAKS studies
The DERBY and OAKS studies are 600-patient prospective, international, multicenter, randomized, double-masked, sham-injection controlled Phase 3 studies assessing the efficacy and safety of multiple IVT injections of pegcetacoplan in patients with GA secondary to AMD. For more information, please visit https://gastudy.com/.
About Pegcetacoplan (APL-2)
Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive complement activation, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b. Apellis is evaluating pegcetacoplan in several clinical studies across hematology, ophthalmology, nephrology, and neurology. Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and the treatment of geographic atrophy, and received orphan drug designation for the treatment of C3 glomerulopathy by the FDA and European Medicines Agency. For additional information regarding our clinical trials, visit https://apellis.com/our-science/clinical-trials.
About Geographic Atrophy (GA)
GA is an advanced form of age-related macular degeneration (AMD), a leading cause of blindness. Excessive complement activation drives irreversible lesion growth in GA,6 and C3 is the only target to precisely control complement overactivation. Pegcetacoplan, studied in early and late-stage trials comprising a total of approximately 1,500 patients, is the only targeted C3 inhibitor being evaluated in late-stage trials to control lesion growth in GA.7
GA lesions affect the central portion of the retina, known as the macula, which is responsible for central vision. GA is progressive and irreversible, leading to central visual impairment and permanent loss of vision. Based on published studies, approximately one million people have GA in the United States and five million people have GA globally.1,2 There are currently no approved treatments for GA.
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop best-in-class and first-in-class therapies for a broad range of debilitating diseases that are driven by uncontrolled or excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visit http://apellis.com.
Apellis Forward-Looking Statement
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether the company’s clinical trials will be fully enrolled and completed when anticipated; whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the company’s clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, C3G, IC-MPGN, ALS, or severe COVID-19 or any other indication when expected or at all; whether, if Apellis’ products receive approval, they will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on July 30, 2020 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
1 Weber, BHF, Issa, PC, et al. The Role of the Complement System in Age-Related Macular Degeneration. Dtsch Arztebl Int 2014; 111(8): 133–8.
2 Heesterbeek, TJ, Lechanteur YTE, et al. Complement activation levels are related to disease stage in AMD. Invest Ophthalmol Vis Sci. 2020; 61(3): 18.
3 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.
4 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.
5 Sunness JS, et al. The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology. 2007 Feb; 114(2):271-7.
6 Seddon, 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.
7 Yates, JRW, Sepp T, et al. Complement C3 Variant and the Risk of Age-Related Macular Degeneration. N Engl J Med 2007; 357.