SYSA1902 Clinically Equivalent to Ustekinumab for Plaque Psoriasis

A recent multicenter, randomized, double-blind, parallel controlled, phase 3 study showed that SYSA1902 has clinical equivalence to ustekinumab in terms of safety, efficacy, pharmacokinetics, and immunogenicity when used to treat moderate-to-severe plaque psoriasis.1

Ustekinumab is one of the most recommended and widely used treatments for plaque psoriasis globally; previous studies indicated its effectiveness in reducing psoriasis area and severity index (PASI) scores.2 SYSA1902 is a generic biosimilar for ustekinumab – early, preclinical studies indicated a similar binding activity between the two treatments.1

“Our findings indicated that the efficacy of SYSA1902 and ustekinumab were similar in the PASI 75 response rate, and other second efficacy endpoints, which resulted in a significantly improved symptoms and quality of life in patients with moderate-to-severe psoriasis,” wrote Lixin Xia, MD, PhD, department of dermatology, The First Hospital of China Medical University, and colleagues.1

The study was conducted across 42 sites in China, involving 446 patients aged 18-75 years who had been diagnosed with moderate-to-severe plaque psoriasis for at least 6 months. Additionally, included participants had baseline psoriasis involving ≥10% of the body surface area (BSA), a PASI score ≥12, and a static physician global assessment (sPGA) score ≥3.1

Xia and colleagues randomized participants in a 1:1 ratio, stratified by weight (<70kg or ≥70 kg), previous treatment with biological agents (yes or no), and presence of psoriatic arthritis (yes or no). 224 patients were given SYSA1902 and 222 were given ustekinumab. By the end of the study, 28 from each group had discontinued for various reasons.1

Safety evaluations were conducted at weeks 6 and 12, and efficacy assessments were performed at baseline and every 4 weeks through 52. Pharmacokinetics and immunogenicity analysis were performed on blood samples collected prior to administration at week 0, 4, 16, 28, and 40, and at any timepoint at week 12, 20, 44, and 52.1

The study’s primary endpoint was the percentage change in PASI from baseline at week 12. Secondary endpoints included percentage change in PASI from baseline at weeks 4-8 and weeks 16-52, percentage of patients achieving PASI 50, 75, 90, and 100 at weeks 4-52, percentage of patients achieving sPGA (0/1) at weeks 4-52, change from baseline in sPGA, BSA, and dermatology life quality index at weeks 4-52, and safety and immunogenicity.1

In the full analysis set, the mean percentage change from baseline in PASI at week 12 was 86.4% in the SYSA1902 group and 84.7% in the ustekinumab group, with a 1.68% difference (95% CI, -1.45 to 4.81). The difference in percentage change was consistent across all subgroups, and all fell within the equivalence margins save for patients with psoriatic arthritis due to lower sample size (n = 17).1

In the safety analysis set, investigators noted that 89.3% of patients in the SYSA1902 group and 85.6% in the ustekinumab group exhibited at least one treatment-emergent adverse event (TAEA). The most common TEAEs were upper respiratory tract infection (SYSA1902 vs ustekinumab 33.0% vs 26.6%), hyperlipidemia (24.6% vs 24.8%), elevated liver enzymes (20.1% vs 13.1%), and increased uric acid levels (14.7% vs 13.1%).1

Pharmacokinetic profiles were comparable between both treatments – treatment-induced anti-drug antibody positivity was exhibited in 37 (16.6%) of 223 patients receiving SYSA1902 vs 62 (28.2%) of 220 patients receiving ustekinumab. Among these, the neutralizing antibody positivity was seen in 18 (48.6%) of 37 SYSA1902 recipients and 30 (48.4%) of ustekinumab recipients.1

Xia and colleagues found that, across all four primary measurements, SYSA1902 and ustekinumab exhibited relative equivalence, thereby achieving the primary endpoint. Additionally, the secondary efficacy endpoints also indicated the similarity between the two treatments.1

“Further studies will be conducted to explore the efficacy and safety of SYSA1902 in the general population with the above characteristics,” Xia and colleagues wrote.1

References

1. Xia L, Miao G, Yang X, et al. Efficacy and safety of SYSA1902 versus reference ustekinumab in moderate-to-severe plaque psoriasis: A Multicenter, randomized, phase III study. Journal of the American Academy of Dermatology. Published online April 10, 2025. doi:10.1016/j.jaad.2025.03.018

2. Zhu X, Zheng M, Song M, et al. Efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis: results from a phase 3 clinical trial (LOTUS). J Drugs Dermatol. 2013;12(2):166-174.