Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial. Ophthalmology Therapeutics
NCT05053659 CTR20190937 | Not reported | Li B et al. (2024)
Li, B., Fan, K., Zhang, T., Wu, Z., Zeng, S., Zhao, M., et al. Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial. Ophthalmology Therapeutics, 2024; 13:353–366.
Locations
35 centers in China
Study Period
August 2019 – January 2022
Study Design
Phase 3, randomized, double-blind, multicenter, parallel-group trial
Study Population
Experimental Group
Control Group
Follow-up Time: 48 weeks
Outcomes
Durability
Number of Injection
The times of study drug injection were similar between the two groups (7.5 ± 1.2 vs. 7.4 ± 1.4).
Vision
Best-Corrected Visual Acuity (BCVA)
The Least-squares mean (LSM) at Week 12 (Primary Outcome):
• QL1207 = +10.4 ± 8.8 letters
• Aflibercept = +11.5 ± 9.2 letters
• Difference = -1.1 letters (95% CI: -3.0 to 0.7, p = 0.2275).
Other
N/A
Immunognicity
Positive anti-drug antibody (ADA) rates:
• QL1207: 7.1%
• Aflibercept: 7.7%
• No significant differences in neutralizing antibody formation.
Pharmokinetics
Plasma free VEGF levels and pharmacokinetic parameters were similar between QL1207 and reference aflibercept.
Anatomic
Change in Central Retinal Thickness (CRT)
The LSM change at Week 52:
• QL1207 = -183.0 ± 12.1 µm
• Aflibercept = -208.4 ± 12.4 µm
• Difference = 25.4 µm (95% CI: -6.4 to 57.1, p = 0.1171).
Change in CNV Leakage Area
The LSM CNV leakage area change at Week 52:
• QL1207 = -2.72 ± 0.26 mm²
• Aflibercept = -2.61 ± 0.26 mm²
• Difference = -0.11 mm² (95% CI: -0.77 to 0.55, p = 0.7397).
Safety
Treatment-emergent AEs (TEAEs)
• QL1207: 132/185, 71.4%
• Aflibercept: 130/181, 71.8%
Serious AEs
• QL1207: 26/185, 14.1%
• Aflibercept: 23/181, 12.7%.
Ocular TEAEs
Ocular TEAE in the study eye:
• QL1207: 52/185, 28.1%
• Aflibercept: 54/181, 29.8%
Ocular TEAE in the fellow eye:
• QL1207: 36/185, 19.5%
• Aflibercept: 25/181, 13.8%
Non-ocular TEAEs
• QL1207: 111/185, 60.0%
• Aflibercept: 103/181, 56.9%.
Study drug-related AEs
• QL1207: 5.9%
• Aflibercept: 8.3%.
Conclusion
QL1207 demonstrated equivalent efficacy and similar safety profiles compared to aflibercept for nAMD treatment, supporting its use as an alternative anti-VEGF agent.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Randomization was stratified…at baseline using Interactive Web Response System.” “The baseline characteristics were well balanced between the two groups in the FAS.”
Missing Outcome Data
Low risk
Note: Evidence that the result was not biased by missing outcome data: “The per-protocol set (PPS) was used for supplementary analysis”
Selection of the Reported Results
Low risk Note: registration with the protocol.
Deviations from Intended Observations
Low risk Note: “Patients and assessors (including the central reading centers) …were blind to allocation.” “The efficacy endpoints were evaluated in the full analysis set (FAS).”
Measurement of the Outcome
Some concerns Note: This is a double-blind study. However, this is a multiple-site study. There is no information on if the primary outcome assessment is consistent across all sites. However, assessment of the outcome could not have been influenced by knowledge of intervention received.
Overall
Some concerns
Categories: Wet AMD