Similar Efficacy and Safety of Biosimilar Candidate IBI303 and Reference Products of Adalimumab in Patients with Ankylosing Spondylitis : Results from a Randomized, Double-Blind, Phase III Study

Xu Huji¹, Li Zhijun², Wu Jian³, Xing Qian⁴, Guixiu Shi⁵, Li Juan⁶, Liu Xu⁷, Lijun Wu⁸, Li Xiaomei⁹, Tan Wenfeng¹⁰, Dongyi He¹¹, Bi Liqi¹², Li Hongbin¹³, Xiao Zhengyu¹⁴, Shuai Zongwen¹⁵, Li Xiaoxia¹⁶, Wang Yongfu¹⁷, Luo Li¹⁸, Zheng Yi¹⁹, Xiao Weiguo²⁰, Zhou Hui²¹, Lu Yushan²¹, Zheng Shirui²¹ and Wang Xiong²¹, ¹Shanghai Changzheng Hospital, Shanghai, China, ²The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, ³The First Affiliated Hospital of Soochow University, Suzhou, China, ⁴Qingdao municipal hospital, Qingdao, China, ⁵The First Affiliated Hospital of Xiamen University, Xiamen, China, ⁶Nanfang Hospital, Southern Medical University, Guangzhou, China, ⁷Peking University People’s Hospitalv, Beijing, China, ⁸People's Hospital of Xinjiang Uygur Autonomous Region, Wulumuqi, China, ⁹Anhui Provincial Hospital, Hefei, China, ¹⁰Jiangsu Province Hospital, Nanjing, China, ¹¹Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China, ¹²China-Japan Friendship Hospital, Changchun, China, ¹³The Affiliated Hospital of Inner Mongolia Medical University, Huhehaote, China, ¹⁴The First Affiliated Hospital of Shantou University Medical College, Shantou, China, ¹⁵The First Affiliated Hospital of Anhui Medical University, Hefei, China, ¹⁶Xuanwu Hospital Capital Medical University, Beijing, China, ¹⁷The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science & Technology, Baotou, China, ¹⁸The First Affiliated Hospital of XinJiang Medical University, Wulumuqi, China, ¹⁹Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China, ²⁰The First Hospital of China Medical University, Shenyang, China, ²¹Innovent Biologics (Suzhou) Co. Ltd, Shanghai, China

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Adalimumab, ankylosing spondylitis (AS) and biosimilars

Session Information

Date: Tuesday, October 23, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster III: Treatment

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: IBI303, an injection of recombinant human anti-tumor necrosis factor-α monoclonal antibody, is adalimumab biosimilar candidate. Physicochemical properties assessment and non-clinical studies showed the structure, pharmacodynamics and pharmacokinetics of IBI303 were similar to adalimumab. This study compared the efficacy and safety of IBI303 with adalimumab in patients with ankylosing spondylitis (AS).

Methods: This was a randomized, double-blind, and adalimumab-controlled phase III clinical study. Patients met the classification criteria of the 1984 modified New York criteria for AS and in active disease were enrolled, and assigned to IBI303 or adalimumab groups in 1:1 ratio. The primary endpoint was the percentage of patients achieving the Assessment of SpondyloArthritis International Society (ASAS) 20 response criteria at week 24. Patients without data at week 24 were treated as non-responders. The safety and immunogenicity of the two groups were also compared.

Results: A total of 438 patients were randomized (IBI303, n=220; adalimumab, n=218) . Baseline demographics were generally similar between the two groups. At week 24, there were 75.0%（165/220） and 72.5%（158/218）patients achieved ASAS20 response in IBI303 and adalimumab group, respectively, and 95% confidence interval (CI) of differences between the two groups was -5.7% to 10.8%, indicating the IBI303 was equivalence to that of adalimumab in efficacy. Results of other efficacy endpoints were comparable between the two groups (Table 1). The overall incidence of adverse events (AEs) was 79.1% for IBI303 group and 81.7% for adalimumab group, respectively (Table 2). The most common AEs in IBI303 group were upper respiratory tract infection (24.5%), alanine aminotransferase increased (12.7%) and hyperuricaemia (10.5%), while in adalimumab group were upper respiratory tract infection (20.6%), alanine aminotransferase increased (19.3%) and Aspartate aminotransferase increased (10.6%). The positive rate of antidrug antibodies was 58.6% and 61.9%, and the positive rate of neutralizing antibodies was 46.5% and 51.1% in IBI303 and adalimumab group, but had no observable impact on ASAS20 response.

Conclusion: This study demonstrated IBI303 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe AS.

Table 1. ASAS response rates at week 24 (Full analysis set)

	IBI303 N=220 n (%)	Adalimumab N=218 n (%)	difference (95%CI)	P value
ASAS20	165（75.0）	158（72.5）	2.5% (-5.7%, 10.8%)	0.5732
ASAS40	137（62.3）	134（61.5）	0.8%（-8.3%, 9.9%）	0.8636
ASAS partial remission	65（29.5）	74（33.9）	-4.4%（-13.1%, 4.3%）	0.3724

Table 2. Summary of AEs

	IBI303 N=220 n (%)	Adalimumab N=218 n (%)
Treatment-emergent adverse events	174 (79.1)	178 (81.7)
Significant AEs	119 (54.1)	113 (51.8)
Serious adverse events	7 (3.2)	8 (3.7)
AEs leading to study discontinuation	6 (2.7)	5 (2.3)

Disclosure: X. Huji, None; L. Zhijun, None; W. Jian, None; X. Qian, None; G. Shi, None; L. Juan, None; L. Xu, None; L. Wu, None; L. Xiaomei, None; T. Wenfeng, None; D. He, None; B. Liqi, None; L. Hongbin, None; X. Zhengyu, None; S. Zongwen, None; L. Xiaoxia, None; W. Yongfu, None; L. Li, None; Z. Yi, None; X. Weiguo, None; Z. Hui, Innovent Biologics (Suzhou) Co. Ltd, 3; L. Yushan, Innovent Biologics (Suzhou) Co. Ltd, 3; Z. Shirui, Innovent Biologics (Suzhou) Co. Ltd, 3; W. Xiong, Innovent Biologics (Suzhou) Co. Ltd, 3.

To cite this abstract in AMA style:

Huji X, Zhijun L, Jian W, Qian X, Shi G, Juan L, Xu L, Wu L, Xiaomei L, Wenfeng T, He D, Liqi B, Hongbin L, Zhengyu X, Zongwen S, Xiaoxia L, Yongfu W, Li L, Yi Z, Weiguo X, Hui Z, Yushan L, Shirui Z, Xiong W. Similar Efficacy and Safety of Biosimilar Candidate IBI303 and Reference Products of Adalimumab in Patients with Ankylosing Spondylitis : Results from a Randomized, Double-Blind, Phase III Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/similar-efficacy-and-safety-of-biosimilar-candidate-ibi303-and-reference-products-of-adalimumab-in-patients-with-ankylosing-spondylitis-results-from-a-randomized-double-blind-phase-iii-study/. Accessed .

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