Biosimilar Aflibercept P041 as Effective, Safe as Originator in nAMD

Biosimilar aflibercept (P041) demonstrated comparable safety and efficacy to the originator aflibercept (Eylea) in treating patients with retinal conditions like neovascular age-related macular degeneration (nAMD). | Image Credit: Yakobchuk Olena - stock.adobe.com

Biosimilar aflibercept (P041) exhibited similar effectiveness and safety as originator aflibercept (Eylea) in retinal conditions like neovascular age-related macular degeneration (nAMD), according to a study published in the American Academy of Ophthalmology.¹

Both patients with AMD and nAMD have retinal conditions caused by choroidal neovascularization that impairs vision. Vascular endothelial growth factor (VEGF) is heavily responsible in active intraocular neovascularization and preventing VEGF can treat neovascular disease.

The reference product received FDA approval for patients with nAMD in November 2011 following the positive results from the VIEW 1 and VIEW 2 studies.² The first 2 biosimilars referencing aflibercept came a little over 10 years later, with the approval of aflibercept-yszy (Opuviz) and aflibercept-jbvf (Yesafili) in the latter half of May 2024.³

Majority of the population with AMD or nAMD is elderly, thus biosimilar options offer accessible treatment that is priced lower than the reference products, significantly beneficial for those living on fixed incomes after reaching retirement.¹

“The aim of this trial was to assess the efficacy, safety, and immunogenicity of P041 in comparison with the reference aflibercept over 52 weeks,” stated the study authors.

Participants were enrolled in a phase 3 randomized, double-masked active control trial over a 52-week duration across multiple centers. Patients were randomly assigned either biosimilar aflibercept (P041) or the reference product (Eylea) via intravitreal injections. Both groups received treatment every 4 weeks with 3 loading doses then every 8 weeks until week 48.

The primary outcome was to evaluate the noninferiority of intravitreal P041 compared with originator aflibercept at week 52. The secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity throughout the study.

The study included 1 individual eye from 168 patients who were each randomly assigned to a study arm, both groups evenly split into 84 participants each (P041, originator aflibercept) with an average age of 68 years. Of the 168 patients, there were 145 who completed the study for the entire 52 weeks (P041, n = 72; aflibercept, n = 73).

By week 52, 94.44% of patients in the P041 group and 94.52% in the aflibercept group maintained their vision from baseline. No significant differences were identified between the 2 groups (difference, –0.0008; 95% CI, –0.074-0.074; P = .98).

Both groups demonstrated a percentage of 93.98% of patients who maintained vision (difference, 0; 95% CI, –0.072-0.072; P = 1). The predefined noninferiority margin was lower than the percentage difference.

Secondary outcomes found no significant differences between the 2 groups and best corrected visual acuity improved in both arms as well (P = .96). Across the P041 biosimilar arm and the originator aflibercept group, all differences were considered nonsignificant (all P > .05). Immunogenicity ruled efficacy date proved the treatment could maintain visual acuity, change central subfield thickness, and achieve a dry macula by week 52.

Adverse events (AEs) were present among 44 patients in the aflibercept originator group and 47 patients in the P041 biosimilar group. Injection site irritation and rhinorrhea were the most reported ocular AE and the most reported nonocular AE, respectively, for both groups.

The COVID-19 pandemic disrupted the study, resulting in limited visitations and follow-up schedules for some patients. Data was also reviewed by a research coordinator but the evaluation of the images in an image reading center may improve the validity of data.

“This phase 3 clinical trial showed P041 is noninferior to aflibercept in terms of maintaining vision,” concluded the study authors. “Other efficacy and safety outcomes were also similar between the 2 products through 52 weeks of the study.”

References

1. Karkhaneh R, Faghihi H, Riazi-Esfahani H, et al. Evaluating the efficacy and safety of aflibercept biosimilar (P041) compared with originator product in patients with neovascular age-related macular degeneration. Ophthalmology Retina. 2024;8(8):744-753. doi:10.1016/j.oret.2024.02.012

2. Regeneron announces Eylea (aflibercept ophthalmic solution) receives unanimous recommendation for approval for treatment of wet AMD from FDA advisory committee. Drugs.com. November 18, 2011. Accessed October 28, 2024. https://www.drugs.com/nda/eylea_110617.html

3. Jeremias S. FDA approves first Eylea biosimilars. The Center for Biosimilars^®. May 20, 2024. Accessed October 28, 2024. https://www.centerforbiosimilars.com/view/fda-approves-first-eylea-biosimilars