Biosimilar QL1207 Confirms Equivalent Efficacy to Reference Aflibercept

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Results from a randomized, double-blind, phase 3 trial provided new insight into the efficacy and safety profile of QL1207, an aflibercept biosimilar, in the treatment of neovascular age-related macular degeneration (nAMD).¹

Data from the phase 3 trial showed the difference in best-corrected visual acuity (BCVA) changes from baseline at 12 weeks was within the predefined equivalence margin between the biosimilar QL1207 and reference aflibercept treatment groups.

Thus, the investigative team, led by Bing Li of the department of ophthalmology at Peking Union Medical College Hospital, suggested QL1207 may serve as an alternative anti-vascular growth factor (VEGF) agent for clinical practice.

“The totality of evidence for QL1207 supports it as the first aflibercept biosimilar and an alternative option for patients with nAMD in China,” Li and colleagues wrote.

A leading cause of global visual impairment and blindness, the pathogenesis of nAMD is not confirmed, but likely results from factors including inflammation, oxidative stress, and lipid metabolism. VEGF also plays a crucial role in retinal diseases and anti-VEGF treatments are now considered the standard-of-care.

QL1207 is the first biosimilar aflibercept in China, with preclinical studies suggesting the medicine is comparable to the reference product. The phase 3 trial sought to evaluate the equivalence of efficacy, the similarity of safety, immunogenicity, and pharmacokinetics (PK) between biosimilar QL1207 and reference aflibercept.

The trial was conducted at 35 centers in China—key eligibility criteria included an age ≥50 years, untreated subfoveal choroidal neovascularization (CNV) secondary to nAMD, and BCVA letter score of 73–34 using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Eligibility was determined through medical history, ophthalmic and physical examination, optical coherence tomography (OCT), and fluorescein angiography (FA) before randomization in the screening period.

Patients matching inclusion criteria were randomly assigned 1:1 to receive intravitreal QL1207 or aflibercept 2 mg in the study eye every 4 weeks during the first 3 months, followed by 2 mg every 8 weeks until week 48. Randomization was stratified by BCVA ≥ or ≤45 letters at baseline. The primary trial endpoint was considered the change in BCVA from baseline to week 12, with an equivalence margin of ± 5.

The trial screened 533 patients from August 2019 to January 2022, with 366 enrolled and randomized to the QL1207 (n = 185) or aflibercept group (n = 181). Baseline characteristics of the population were well-balanced between the two groups in the full analysis set. In particular, the mean BCVA was 56.1 ± 11.7 letters in the QL1207 group and 56.3 ± 11.8 letters in the aflibercept group at baseline.

Upon analysis, the mean BCVA changes from baseline at week 12 were 10.2 ± 8.8 letters in the QL1207 group and 11.0 ± 9.2 letters in the aflibercept group. The least-squares mean changes in BCVA from baseline were 10.4 letters vs. 11.5 letters in the two groups, for a difference of –1.1 letters (95% CI, –3.0 to 0.7; P = .2275). As the difference was within the equivalence margin of ± 5, investigators were able to confirm the efficacy equivalence of QL1207 and the reference aflibercept.

Safety data revealed the incidence of treatment-emergent adverse events (TEAE) was comparable between QL1207 and reference aflibercept (132 [71.4%] vs. 130 [71.8%]). TEAEs were considered related to the study drug in 11 (5.9%) and 15 (8.3%) patients in the two cohorts, respectively. Serious TEAE were identified in 26 (14.1%) and 23 (12.7%) patients in the two groups, but none were considered related to the study drug.

Immunogenicity profiles identified similar incidences of positive anti-drug antibodies (ADA) between the two groups (7.1% vs. 7.7%). Li and colleagues also confirmed the pharmacokinetic profiles and plasma VEGF concentrations were comparable between groups, irrespective of free or bound state.

“This study indicated that QL1207 had potent efficacy, acceptable safety, immunogenicity, and PK profile similar to the aflibercept on the treatment of nAMD,” investigators wrote.

References

1. _{Li, B., Fan, K., Zhang, T. 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. Ophthalmol Ther 13, 353–366 (2024). https://doi.org/10.1007/s40123-023-00836-4}
2. _{Ardeljan D, Chan CC. Aging is not a disease: distinguishing age-related macular degeneration from aging. Prog Retin Eye Res. 2013 Nov;37:68-89. doi: 10.1016/j.preteyeres.2013.07.003. Epub 2013 Aug 9. PMID: 23933169; PMCID: PMC3830684.}