Ankylosing spondylitis is a chronic inflammatory disease that primarily affects the sacroiliac joints and spine, causing persistent pain, stiffness and declining function. Although multiple biologic drugs are currently available for clinical treatment, a large number of patients cannot achieve stable and ideal disease control after conventional and targeted therapy, which is a long-standing unmet clinical problem. Because IL-17A and IL-17F can act synergistically to amplify inflammation, dual inhibition has been proposed as a strategy that may provide broader inflammatory control.
This large-scale long-term clinical study confirms that the independently developed dual-target antibody XKH004 can effectively and stably improve various symptoms and physical functions of patients with active ankylosing spondylitis over 52 weeks of treatment. Compared with placebo treatment, XKH004 significantly increases the proportion of patients achieving standard clinical remission. It not only quickly relieves back pain and morning stiffness, but also continuously reduces systemic inflammation, improves spinal mobility and patients’ daily living ability. Meanwhile, the long-term safety performance of the drug is stable and controllable, without additional adverse reaction risks, proving its value for long-term standardized treatment of ankylosing spondylitis.
“Different from traditional single-target IL-17 inhibitors, XKH004 can simultaneously block two core inflammatory factors, IL-17A and IL-17F, which fundamentally compensates for the insufficient anti-inflammatory effect of existing drugs. The 52-week complete clinical data fully verify that this domestic innovative drug has both excellent curative effect and long-term safety, and will provide a new reliable treatment option for refractory ankylosing spondylitis patients who have poor response to existing therapies,” said Professor Huji Xu, Chief of the Department of Rheumatology and Immunology, Changzheng Hospital, Naval Medical University.
The superior clinical efficacy of XKH004 stems from its unique dual-target pharmacological mechanism. As a novel humanized IgG1 monoclonal antibody, it can specifically neutralize both IL-17A and IL-17F, completely block the synergistic pro-inflammatory cascade reaction of the two key pathogenic factors, and achieve more comprehensive inflammatory suppression than single-target drugs. This study adopts a multi-center, randomized, double-blind, placebo-controlled phase III clinical design with rigorous experimental logic and a large sample size. It sets standardized multi-time-point and multi-dimensional evaluation indicators covering disease activity, physical function, pain degree, inflammatory level and quality of life, and monitors adverse events and drug immunogenicity throughout the whole cycle, ensuring the authenticity, reliability and clinical practicability of the research results.
This 52-week long-term clinical study fills the research gap of long-term efficacy and safety of domestic dual-target IL-17A/F antibodies in the treatment of ankylosing spondylitis, and provides high-level evidence-based medical support for the clinical application of XKH004. As a domestically originated biologic agent, XKH004 offers a safe and effective alternative for patients with suboptimal responses to existing targeted therapies, greatly expanding the current treatment landscape for ankylosing spondylitis.
The work was conducted by researchers at Changzheng Hospital, Naval Medical University, together with investigators from 36 other clinical centers in China. Support was provided by the National Natural Science Foundation of China (82320108010 and 31821003), the National Key Research and Development Project (2018AAA0100302), Shanghai Municipal Key Clinical Specialty (shslczdzk02602), and Shanghai Science and Technology Development Funds (2020-SH-XY-2). Kanova Biopharmaceutical Co., Ltd. participated in study design, supplied XKH004 and placebo, and contributed to statistical analysis. The trial was registered as CTR20232310 and NCT07498634.
About Author
Professor Huji Xu is director of the Department of Rheumatology and Immunology at Changzheng Hospital, Naval Medical University, and deputy director of the National Key Laboratory for Immunity and Inflammation. He also holds academic appointments at Tsinghua University School of Medicine and the Tsinghua-Peking Center for Life Sciences. As Chief Scientist of China’s National Basic Research Program (973 Program), his research focuses on translational diagnosis and innovative treatment of rheumatic and immune-mediated diseases, including ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus. Until now, he has published more than 280 papers in Nature , Cell , Nature Medicine , The Lancet Rheumatology , and other journals, presided over dozens of national key scientific research projects, and received multiple municipal-ministerial first-class science and technology awards.
D OI Link:
https://doi.org/10.1016/j.hlife.2026.07.005
hLife
Efficacy and safety of XKH004, a novel dual interleukin-17A/F inhibitory monoclonal antibody, in active ankylosing spondylitis: A 52-week phase 3 randomized study
8-Sep-2026