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Clinical Trial
. 2022 Jan;39(1):583-597.
doi: 10.1007/s12325-021-01899-0. Epub 2021 Nov 23.

Efficacy and Safety of HLX03, an Adalimumab Biosimilar, in Patients with Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blind, Phase III Study

Lin Cai  1 , Linfeng Li  2 , Hao Cheng  3 , Yangfeng Ding  4 , Zhenshu Biao  5 , Shifa Zhang  6 , Songmei Geng  7 , Quanzhong Liu  8 , Hong Fang  9 , Zhiqi Song  10 , Yan Lu  11 , Shanshan Li  12 , Qing Guo  13 , Juan Tao  14 , Li He  15 , Jun Gu  16 , Qinping Yang  17 , Xiuping Han  18 , Xinghua Gao  19 , Danqi Deng  20 , Shenqiu Li  21 , Qingyu Wang  22 , Jun Zhu  22 , Jianzhong Zhang  23
Affiliations
Clinical Trial

Efficacy and Safety of HLX03, an Adalimumab Biosimilar, in Patients with Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blind, Phase III Study

Lin Cai et al. Adv Ther. 2022 Jan.

Abstract

Introduction: Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis.

Methods: In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated.

Results: In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI - 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups.

Conclusion: HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China.

Clinical trial registration: Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017).

Keywords: Adalimumab; Biosimilar; Plaque psoriasis; TNFα inhibitor.

Plain language summary

Plaque psoriasis is a chronic, autoimmune, inflammatory skin disease associated with significant morbidity and reduced quality of life. In China, the prevalence of plaque psoriasis increased four-fold between 1987 and 2012. Adalimumab is a biologic antibody used to treat plaque psoriasis globally. However, high treatment costs remain as a significant barrier to adalimumab therapy. Therefore, HLX03 has been developed as an adalimumab (Humira®) biosimilar, which is almost identical to the licensed reference adalimumab, but less expensive and more accessible to patients. In this randomized clinical trial, the efficacy (ability of a drug to produce the desired treatment effects), safety, and immunogenicity (ability of a drug to induce immune response which would affect its efficacy and safety) of HLX03 were compared with the reference adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. Efficacy was evaluated by comparing the changes in severity and extent of disease using Psoriasis Area and Severity Index score between treatment initiation and week 16. Safety was monitored by adverse events, laboratory tests and vital signs. Immunogenicity was assessed by the incidence of antidrug antibodies. Among the 262 randomized patients, 131 received HLX03 and 130 received adalimumab. Both groups reported similar improvements in Psoriasis Area and Severity Index scores (between-group difference fell within the prespecified equivalence margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety and immunogenicity profiles. In summary, HLX03 demonstrated equivalent efficacy to adalimumab, validating it as an alternative treatment for patients with plaque psoriasis in China.

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Figures

Fig. 1
Fig. 1
Patient disposition. *Time of primary efficacy endpoint: percentage improvement in PASI score from baseline to Week 16. †FAS includes all randomized patients who received at least one dose of the study drug and had baseline values and at least one post-dose efficacy evaluation. ‡PPS includes all patients in the FAS who had no major protocol violations. Ten treated patients were excluded from the PPS in the HLX03 group (seven patients with < 16 weeks of dosing, two patients for not receiving study treatment at some visits and one patient for use of prohibited drugs). Twelve treated patients were excluded from the PPS in the adalimumab group (eight patients with < 16 weeks of dosing, one patient for not receiving study treatment at some visits, two patients for use of prohibited drugs and one patient erroneously injected with the drug meant for other patients). §Safety population includes all patients who received at least one dose of the study drug and had post-dose safety evaluation data. FAS full analysis set, PASI Psoriasis Area and Severity Index, PPS per protocol set
Fig. 2
Fig. 2
Percentage improvement in PASI over time through week 50 (FAS). FAS full analysis set, LS least square, PASI Psoriasis Area and Severity Index, SE standard error
Fig. 3
Fig. 3
Percentage of patients achieving a PASI 75 and b PGA 0/1 over time through week 50 (FAS). FAS full analysis set, PASI 75 an improvement in Psoriasis Area and Severity Index of at least 75% relative to baseline, PGA 0/1 Physician’s Global Assessment of clear or almost clear
Fig. 4
Fig. 4
Change in DLQI over time through week 50 (FAS). DLQI Dermatology Life Quality Index, FAS full analysis set, LS least square, SE standard error
See this image and copyright information in PMC

References

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