Efficacy and safety of the proposed biosimilar aflibercept, SDZ-AFL, in patients with neovascular age-related macular degeneration: 52-week results from the Phase 3 Mylight study
NCT04864834 | Mylight | Bordon AF et al. (2024)
Bordon, A. F., Kaiser, P. K., Wolf, A., Cen, L., Heyn, J., Urosevic, D., Dodeller, F., Allmannsberger, L., & Silva, R. Efficacy and safety of the proposed biosimilar aflibercept, SDZ-AFL, in patients with neovascular age-related macular degeneration: 52-week results from the Phase 3 Mylight study. Retina, 2024; 44(10):1704-1713.
Locations
103 sites in 16 countries across North America, Europe, Asia, and Australia
Study Period
May 2021 to January 2024
Study Design
Phase 3, prospective, randomized, multicenter, double-masked, parallel-arm trial
Study Population
Experimental Group
Control Group
Follow-up Time: 12 months
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change at Week 8 (Primary Outcome):
• SDZ-AFL = +5.2 letters
• Ref-AFL = +5.5 letters
• Difference = -0.3 letters (90% CI: -1.5 to 1.0, p = 0.62).
Mean BCVA change at Week 52:
• SDZ-AFL = +7.1 letters
• Ref-AFL = +7.5 letters
• Difference = -0.4 letters (95% CI: -1.8 to 1.0, p = 0.53).
Proportion of Patients Losing <15 Letters BCVA
At Week 52:
• SDZ-AFL: 16.7%
• Ref-AFL: 17.2%
• Difference = -0.44% (95% CI: -7.35 to 6.46).
Proportion of Patients Gaining ≥15 Letters BCVA
At Week 52:
• SDZ-AFL: 20.3%
• Ref-AFL: 23.8%
• Difference = -3.52% (95% CI: -11.14 to 4.09, p = 0.35).
Other
N/A
Immunognicity
Pre-existing ADAs:
• SDZ-AFL: 1.2%
• Ref-AFL: 1.7%.
Newly Developed ADAs:
• SDZ-AFL: 0.9%
• Ref-AFL: 2.6%.
Pharmokinetics
Systemic free aflibercept concentrations 24 hours post-dose was low and comparable between groups.
Anatomic
Change in Central Subfield Thickness (CSFT)
Mean CSFT change at Week 52:
• SDZ-AFL = -193.4 µm
• Ref-AFL = -189.6 µm
• Difference = -3.8 µm (95% CI: -14.7 to 7.1, p = 0.48).
Choroidal neovascularization (CNV)
The Mean change in CNV lesion size was comparable between treatment groups at Weeks 8 and 52, respectively.
Presence of intraretinal fluid (IRF)
Week 52:
• 23.9% of participants receiving SDZ-AFL had IRF
• 24.3% of those who received Ref-AFL
• risk difference: -0.45 (95% CI, -8.407 to 7.5057)
Safety
Treatment-emergent AEs (TEAEs)
No. of subjects with at least one TEAE:
• SDZ-AFL: 73.4%
• Ref-AFL: 72.5%
TEAE suspected to be treatment-related:
• SDZ-AFL: 2.5%
• Ref-AFL: 2.9%
Severe TEAE suspected to be treatment-related:
• SDZ-AFL: 0.4%
• Ref-AFL: 0
Serious AEs
Total:
• SDZ-AFL: 16.0%
• Ref-AFL: 12.5%
Suspected to be treatment related:
• SDZ-AFL: 0.6%
• Ref-AFL: 0.4%.
Ocular TEAEs (study eyes)
Suspected to be related to the study procedure:
• SDZ-AFL: 11.5%
• Ref-AFL: 10.8%
Suspected to be related to study procedure and study drug:
• SDZ-AFL: 0.4%
• Ref-AFL: 0.4%
TEAE leading to study drug discontinuation
• SDZ-AFL: 4.5%
• Ref-AFL: 3.3%
AE leading to death
• SDZ-AFL: 2.0%
• Ref-AFL: 0.4%.
Conclusion
SDZ-AFL and Ref-AFL are comparable in efficacy, safety, and pharmacokinetics in patients with neovascular age-related macular degeneration. This Phase 3 study confirms the biosimilarity of SDZ-AFL to Ref-AFL.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: No information of the allocation concealment or randomization. However, “Treatment groups were well balanced across their baseline characteristics and Demographics.”
Missing Outcome Data
Low risk
Note: Sensitivity analysis was performed to confirm hat the result was not biased by missingness.
Selection of the Reported Results
Low risk Note: Registration with protocol.
Deviations from Intended Observations
Low risk Note: This is a double-masked study. Both per protocol set and full analysis set were performed for the primary outcome analysis.
Measurement of the Outcome
Some concerns Note: This is a double-masked 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