Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration
NCT05587062 | Not reported | Karkhaneh R et al. (2024)
Karkhaneh, R., Faghihi, H., Riazi-Esfahani, H., Abrishami, M., Bazvand, F., Ebrahimiadib, N., Johari, M., Akhlaghi, M., Shoeibi, N., Norouzzadeh, M. 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; 8:744-753.
Locations
12 medical centers in Iran
Study Period
October 2019 – July 2022
Study Design
Phase III, multicenter, randomized, double-masked, active control trial
Study Population
Experimental Group
Control Group
Follow-up Time: 52 weeks
Outcomes
Durability
N/A
Vision
Maintaining Vision
Primary Outcome: the proportion of patients maintaining vision (a loss of < 15 letters) at week 52:
• 94.4% in the P041 group compared with 94.5% in the AFL group.
• The 95% confidence interval (CI) for the difference in maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference=-0.0008; 95% CI: 0.074 to 0.074; P = 0.98).
Mean Change in BCVA (ETDRS Letters)
The mean changes from baseline to week 52:
• P041: +7.95 (SD 17.61)
• AFL: +6.91 (SD 12.98)
• Difference = -0.13 (95% CI: -4.79 to 4.53, p = 0.96)
Proportion Gaining ≥15 Letters
The percentage of eyes with BCVA gain ≥15 letters from week 0 to week 52
• P041: 33.7% vs. AFL: 25.3% (p = 0.23)
Other
N/A
Immunognicity
One patient in P041 group tested positive for antidrug antibodies at Week 52 but maintained visual and anatomic response.
Pharmokinetics
Not reported
Anatomic
Change in Central Subfield Thickness (CST)
At week 52:
• P041: -167.3 µm (SD 189.1)
• Aflibercept: -148.4 µm (SD 109.6)
• Difference = -1.68 (95% CI: -40.4 to 37.0, p = 0.93).
Intraretinal fluid (IRF) and subretinal fluid (SRF)
• At the end of the study, the percentages of patients with no IRF or SRF were 63.75% and 54.88% in the P041 and Aflibercept patients, respectively (P = 0.25).
• In the P041 group, 61.25% exhibited the resolution of IRF at week 12 based on OCT, whereas in the Aflibercept group, 64.63% showed IRF resolution.
• SRF was resolved in 73.75% of patients in the P041 group and 69.51% in the Aflibercept group.
Safety
Patients experienced ≥ 1 AE
• P041= 47/84, 55.9%
• Aflibercept= 44/84, 52.4%
Any ocular AE
• P041= 38/84, 45.2%
• Aflibercept= 36/84, 42.8%
Any Nonocular AE
• P041= 30/84, 35.7%
• Aflibercept= 25/84, 29.8%
Serious AEs
Total event number:
• P041: 9 cases
• Aflibercep: 12 cases
Patients with ocular SAEs:
• P041= 2/84, 2.4%
• Aflibercept= 1/84, 1.2%
Patients with non-ocular SAEs:
• P041= 5/84, 6.0%
• Aflibercept= 5/84, 6.0%
Conclusion
P041 demonstrated non-inferiority to originator aflibercept, with similar efficacy, safety, and immunogenicity profiles at 52 weeks, supporting its use as a biosimilar treatment for nAMD.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: Randomization “using block randomization (with block sizes of 2 or 4) for generated by R-CRAN software version 3.2.3.” and baseline characteristics look balanced.
Missing Outcome Data
Low risk
Note: Evidence that the result was not biased by missing outcome data: “To conduct a sensitivity analysis for the primary end point, the primary analysis was performed using both per-protocol (PP) and intention-to-treat (ITT) sets.”
Selection of the Reported Results
Low risk Note: Registration with protocol
Deviations from Intended Observations
Low risk Note: “…all patients, clinical investigators, and data assessors were masked...”and ITT principle applied for the primary analysis.
Measurement of the Outcome
Some concerns Note: “…all patients, clinical investigators, and data assessors were masked...” As this is a multiple site study, the assessment for the primary outcome may exist difference. However, assessment of the outcome unlikely to be influenced by knowledge of intervention received
Overall
Some Concerns
Categories: Wet AMD