Vunakizumab Meets Primary Endpoint in axSpA

A novel anti–interleukin (IL)-17A monoclonal antibody, vunakizumab, significantly improved disease activity in adults with radiographic axial spondyloarthritis (r-axSpA) compared with placebo at 16 weeks in a randomized, double-blind, placebo-controlled adaptive phase 2/3 trial conducted across 38 hospitals in China, according to findings published in JAMA Network Open.¹

The results add to a growing body of evidence supporting IL-17A pathway inhibition in r-axSpA, where secukinumab, ixekizumab, and the dual IL-17A/F inhibitor bimekizumab are already approved.² Vunakizumab is currently approved in China for moderate-to-severe plaque psoriasis but has not received regulatory approval for any spondyloarthritis indication.¹

“In this randomized clinical trial of patients with r-axSpA, the 120-mg dose of vunakizumab provided significant improvement in signs and symptoms of r-axSpA at week 16, and these clinical benefits were sustained through week 32, with a manageable safety profile. Our findings support vunakizumab as a new treatment option for active r-axSpA,” investigator Jian Zhu, MD, Department of Rheumatology and Immunology, Chinese People’s Liberation Army General Hospital, Beijing, China, and colleagues wrote.¹

The seamless adaptive trial enrolled 548 adults aged 18 years or older with active r-axSpA meeting the modified New York criteria, defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of at least 4 and total back pain score of at least 4, and requiring an inadequate response or intolerance to at least 2 NSAIDs. Patients with prior exposure to 2 or more TNF inhibitors or any prior IL-17, IL-17 receptor, IL-23, or JAK inhibitor use were excluded. Approximately 36% of patients had received prior anti-TNF therapy. The mean (SD) age was 33.0 (8.9) years; 80.3% were male, and 91.5% were HLA-B27 positive.¹

The adaptive design proceeded in 2 stages. In stage 1, patients were randomized 2:2:1 to subcutaneous vunakizumab 120 mg, 240 mg, or placebo at weeks 0, 2, 4, 8, and 12; an interim analysis led the independent data monitoring committee to select 120 mg as the recommended dose for stage 2, in which patients were randomized 2:1 to vunakizumab 120 mg or placebo on the same schedule. The primary endpoint P value for the overall study was derived by combining stage 1 and stage 2 P values via the inverse normal method, with statistical significance set at a 1-sided threshold of P ≤ .025. From week 16 onward, all patients — including those initially assigned to placebo — received vunakizumab 120 mg every 4 weeks through week 32.¹

The primary endpoint — ASAS20 response rate at week 16 — was met. Among patients receiving vunakizumab 120 mg, 65.6% (193 of 294) achieved ASAS20 response, compared with 42.5% (62 of 146) with placebo (difference, 23.2%; 95% CI, 11.8%–34.0%; P <.001). Response was rapid: 34.0% of patients in the vunakizumab group achieved ASAS20 by week 2, versus 11.6% with placebo, and 48.6% versus 26.0% by week 4.¹

All prespecified secondary endpoints at week 16 favored vunakizumab, though these were not adjusted for multiplicity and P values should be considered nominal. ASAS40 response was achieved by 46.3% of vunakizumab-treated patients versus 24.0% with placebo (difference, 22.3%; 95% CI, 13.3%–31.3%; nominal P <.001), and ASAS5/6 response by 55.4% versus 22.6% (difference, 32.8%; 95% CI, 24.0%–41.7%; nominal P <.001). The number needed to treat for 1 additional ASAS20, ASAS40, and ASAS5/6 responder compared with placebo was 4, 4, and 3, respectively. Improvements in BASDAI (least-squares mean change, −2.6 vs −1.7; nominal P <.001), BASFI (−1.7 vs −0.9; nominal P <.001), BASMI (−0.4 vs −0.2; nominal P = .004), AS Quality of Life Questionnaire score (−4.0 vs −2.7; nominal P <.001), and SF-36 Physical Component Summary score (6.3 vs 3.6; nominal P <.001) all significantly favored vunakizumab.¹ In a post hoc analysis, the median ASDAS-CRP at week 16 was 1.7 (IQR, 1.1–2.2) in the vunakizumab group versus 2.6 (IQR, 1.9–3.2) in the placebo group.

Responses were sustained and deepened through the 32-week extension period. Among patients continuing vunakizumab, ASAS20, ASAS40, and ASAS5/6 rates at week 32 reached 77.0%, 62.2%, and 65.4%, respectively. Patients who crossed over from placebo to vunakizumab at week 16 achieved response rates at week 32 similar to those seen in the continuous vunakizumab group.¹

During the placebo-controlled period, overall adverse event (AE) rates were comparable between groups — 83.7% with vunakizumab and 81.5% with placebo. Serious AEs occurred in 1.0% and 0.7% of patients, respectively, and treatment-related serious AEs were rare (0 in the vunakizumab group, 1 in the placebo group). No deaths occurred during the study. Liver enzyme elevations were numerically more common with vunakizumab during the placebo-controlled period: ALT increases were observed in 14.6% versus 4.1%, and AST increases in 6.8% versus 2.1%. Hyperuricemia occurred in 12.6% versus 13.0% of patients, and COVID-19 infection in 12.2% versus 17.1%. No cases of severe infection, opportunistic infection, or malignancy were reported. Injection site reactions occurred in 4.8% of the vunakizumab group versus 2.1% with placebo.¹

Several limitations merit consideration. The trial was conducted entirely in China, limiting direct generalizability to Western patient populations, who differ in HLA-B27 prevalence, anthropometrics, and healthcare-setting practices. Secondary endpoints were not formally tested for multiplicity. The ASDAS-CRP analysis was post hoc. The study duration of 32 weeks does not allow conclusions about longer-term efficacy or safety, including inhibition of radiographic progression. Three of the 29 authors are employees of Jiangsu Hengrui Pharmaceuticals, the study sponsor, which also funded the trial.¹

References

1. Zhu J, Zhao C, Mi C, et al. Vunakizumab for radiographic axial spondyloarthritis: a randomized clinical trial. JAMA Netw Open. 2026;9(5):e2611632. doi:10.1001/jamanetworkopen.2026.11632

2. van der Heijde D, Gensler LS, Deodhar A, et al. Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2020;79(5):595–604. doi:10.1136/annrheumdis-2019-216752