Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial

Bing Li; Ke Fan; Tonghe Zhang; Zhifeng Wu; Siming Zeng; Mingwei Zhao; Qian Ren; Dongping Zheng; Lifei Wang; Xiaoling Liu; Mei Han; Yanping Song; Jian Ye; Cheng Pei; Jinglin Yi; Xian Wang; Hui Peng; Hong Zhang; Zhanyu Zhou; Xiaoling Liang; Fangliang Yu; Miaoqin Wu; Chaopeng Li; Chunling Lei; Jilong Hao; Luosheng Tang; Huiping Yuan; Shanjun Cai; Qiuming Li; Jingxiang Zhong; Suyan Li; Lin Liu; Min Ke; Jing Wang; Hui Wang; Mengli Zhu; Zenghua Wang; Yang Yan; Feng Wang; Youxin Chen

doi:10.1007/s40123-023-00836-4

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. 2024 Jan;13(1):353-366. doi: 10.1007/s40123-023-00836-4. Epub 2023 Nov 21.

Authors

Bing Li^#¹, Ke Fan^#², Tonghe Zhang³, Zhifeng Wu⁴, Siming Zeng⁵, Mingwei Zhao⁶, Qian Ren⁷, Dongping Zheng⁸, Lifei Wang⁹, Xiaoling Liu¹⁰, Mei Han¹¹, Yanping Song¹², Jian Ye¹³, Cheng Pei¹⁴, Jinglin Yi¹⁵, Xian Wang¹⁶, Hui Peng¹⁷, Hong Zhang¹⁸, Zhanyu Zhou¹⁹, Xiaoling Liang²⁰, Fangliang Yu²¹, Miaoqin Wu²², Chaopeng Li²³, Chunling Lei²⁴, Jilong Hao²⁵, Luosheng Tang²⁶, Huiping Yuan²⁷, Shanjun Cai²⁸, Qiuming Li²⁹, Jingxiang Zhong³⁰, Suyan Li³¹, Lin Liu³², Min Ke³³, Jing Wang³⁴, Hui Wang³⁴, Mengli Zhu³⁴, Zenghua Wang³⁴, Yang Yan³⁴, Feng Wang³⁵, Youxin Chen³⁶

Affiliations

¹ Ophthalmology Department, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.
² Ophthalmology Department, Henan Provincial Eye Hospital, Zhengzhou, China.
³ Ophthalmology Department, Jinan Second People's Hospital, Jinan, China.
⁴ Ophthalmology Department, Wuxi Second People's Hospital, Wuxi, China.
⁵ Ophthalmology Department, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, China.
⁶ Ophthalmology Department, Peking University People's Hospital, Beijing, China.
⁷ Ophthalmology Department, Shijiazhuang People's Hospital, Shijiazhuang, China.
⁸ Ophthalmology Department, Shanxi Ophthalmic Hospital, Taiyuan, China.
⁹ Ophthalmology Department, Hebei Eye Hospital, Xingtai, China.
¹⁰ Ophthalmology Department, Eye Hospital, WMU Zhejiang Eye Hospital, Wenzhou, China.
¹¹ Ophthalmology Department, Tianjin Eye Hospital, Tianjin, China.
¹² Ophthalmology Department, General Hospital of Central Theater Command, Wuhan, China.
¹³ Ophthalmology Department, Army Medical Center of PLA, Chongqing, China.
¹⁴ Ophthalmology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁵ Ophthalmology Department, Affiliated Eye Hospital of Nanchang University, Nanchang, China.
¹⁶ Ophthalmology Department, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
¹⁷ Ophthalmology Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹⁸ Ophthalmology Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹⁹ Ophthalmology Department, Qingdao Municipal Hospital, Qingdao, China.
²⁰ Ophthalmology Department, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
²¹ Ophthalmology Department, The First Hospital of Nanchang, Nanchang, China.
²² Ophthalmology Department, Zhejiang Provincial People's Hospital, Hangzhou, China.
²³ Ophthalmology Department, Huai'an First People's Hospital, Huai'an, China.
²⁴ Ophthalmology Department, Xi'an People's Hospital, Xi'an, China.
²⁵ Ophthalmology Department, First Hospital of Jilin University, Changchun, China.
²⁶ Ophthalmology Department, The Second Xiangya Hospital of Center South University, Changsha, China.
²⁷ Ophthalmology Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
²⁸ Ophthalmology Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
²⁹ Ophthalmology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³⁰ Ophthalmology Department, The First Affiliated Hospital of Jinan University, Guangzhou, China.
³¹ Ophthalmology Department, Xuzhou First People's Hospital, Xuzhou, China.
³² Ophthalmology Department, Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
³³ Ophthalmology Department, Wuhan University Zhongnan Hospital, Wuhan, China.
³⁴ Clinical Research Center, Qilu Pharmaceutical Co., Ltd., Jinan, China.
³⁵ Ophthalmology Department, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an, 710004, China. wfoculist@126.com.
³⁶ Ophthalmology Department, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China. chenyx@pumch.cn.

^# Contributed equally.

Abstract

Introduction: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD).

Methods: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated.

Results: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups.

Conclusions: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice.

Trial registration: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Keywords: Aflibercept; Biosimilar; Neovascular age-related macular degeneration; QL1207.

Associated data

ClinicalTrials.gov/NCT05345236