Peter K. Kaiser, MD
Peter K. Kaiser, MD of the Cole Eye Institute at the Cleveland Clinic in Cleveland, Ohio, presented an analysis of intraocular inflammation (IOI) risk factors following abicipar pegol treatment during the Late Breakers session at FLORetina on December 6, 2024.
Introduction to Abicipar Pegol
Abicipar pegol 2 mg administered intravitreally every 8 to 12 weeks has been shown to demonstrate positive visual outcomes in patients with neovascular AMD (nAMD). Abicipar demonstrated noninferiority to standard-of-care ranibizumab administered every 4 weeks in two Phase 3, randomized, controlled clinical trials in patients with treatment-naïve nAMD (CEDAR, NCT02462928;SEQUOIA, NCT02462486).1
Overall, the patients in these trials had stable vision through 52 weeks with no significant differences between those receiving abicipar compared to ranibizumab in mean change from baseline in best corrected visual acuity or central retinal thickness. Despite this promising efficacy data, elevated rates of IOI were observed in those patients receiving abicipar compared to ranibizumab.
“Intraocular inflammation is a serious concern when evaluating treatments administered via intravitreal injections,” stated Dr. Kaiser. “Despite the promising efficacy and durability of abicipar, decreasing the risk of IOI events is the number one priority.”
Clinical Trial Findings Causes of these elevated IOI rates were investigated to better understand overall risk factors of abicipar, with hopes to improve the clinical safety profile while maintaining the long-acting efficacy of the treatment. Clinical safety outcomes and potential risk factors were assessed from a pooled study population from the two randomized Phase 3 trials. However, the analysis of this pooled population did not reveal or identify any single dominant clinical risk factor.
Nonclinical Silicone Oil Study
Dr. Kaiser also shared the results of nonclinical assessments of the role of silicone oil in the presentation of abicipar.
- New Zealand White rabbits were given three intravitreal injections of abicipar from either a syringe known to contain silicone oil (n=13) or from a pre-filled syringe (PFS) known to be free of silicone oil (n=13).
- Silicone oil and proteinaceous particle concentrations were found to be greater than 10-fold higher when abicipar was filled in syringes containing silicone oil compared to silicone oil-free PFS administration, suggesting that silicone oil may increase the risk of clinical IOI.
Conclusions and Implications
These findings suggest that improved clinical safety outcomes may be observed following administration of abicipar from syringes free of silicone oil. Further analyses are being conducted to identify other patient risk factors that may contribute to increased risk of IOI.
Dr. Kaiser concluded, “Understanding the root cause of increased risk of IOI following abicipar treatment allows for improvements in the development process of this novel treatment for nAMD, hopefully leading to more optimal patient outcomes.”
About abicipar pegol
Abicipar pegol is a designed ankyrin repeat protein molecule being developed as a long-acting anti-vascular endothelial growth factor (VEGF) for the treatment of nAMD, with doses administered at fixed 12-week intervals.
About age-related macular degeneration Age-related macular degeneration (AMD) is a progressive retinal degenerative disease and the leading cause of irreversible vision loss in people 50 years of age or older, affecting an estimated 196 million individuals worldwide.2 Neovascular, or “wet” AMD (nAMD), is a severe form of the disease characterized by the choroidal neovascularization or the abnormal growth of blood vessels in the retina.3
Historically, nAMD is treated with anti-VEGFs administered as intravitreal injections. Anti-VEGF therapies inhibit new choroidal neovascularization exudation and may improve visual acuity. However, frequent injections are needed to effectively control the disease. This high treatment burden may lower patient compliance, eventually leading to more advanced disease and vision loss.
References
1. Kunimoto D, Yoon YH, Wykoff CC, et al. Efficacy and Safety of Abicipar in Neovascular Age-Related Macular Degeneration: 52-Week Results of Phase 3 Randomized Controlled Study. Ophthalmology. 2020;127(10):1331-1344. doi:10.1016/j.ophtha.2020.03.035
2. 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(2):e106-e116. doi:10.1016/S2214-109X(13)70145-1
3. Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102(11):1640-1642. doi:10.1001/archopht.1984.01040031330019