Nanobody shows early promise in axSpA

In the first clinical trial for sonelokimab in axial spondyloarthritis (axSpA), most patients achieved at least a 40% improvement in symptoms within the first month, with responses sustained through week 12. These phase 2 findings were accompanied by measurable reductions in inflammatory joint lesions on imaging.

“One important aspect of axSpA is inflammation, and it has an impact on physical function. We can even visualise osteoblast activity in the disease,” explained Prof. Xenofon Baraliakos (Ruhr University, Germany) [1]. Sonelokimab is a nanobody, essentially a monoclonal antibody stripped to its functional core, with a molecular weight of approximately 40 kDa compared with 150 kDa for a conventional antibody. According to Prof. Baraliakos, this smaller size allows the agent to penetrate deep tissues more readily. The current phase 2 study provided the first evidence of robust multidomain efficacy with this approach.

The open-label, single-arm study enrolled 26 patients with typical characteristics of axSpA. All patients had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and had evidence of active disease on MRI and PET scans. Sonelokimab was administered by subcutaneous injection every 2 weeks over an 8-week treatment period. Despite the open-label design, the response rates were notable: more than 80% of patients achieved both Assessment of SpondyloArthritis international Society (ASAS) 40 and ASAS20 responses. Specifically, 77% achieved an ASAS40 response at week 4, increasing to 81% at week 12, with improvements observed across all assessed disease domains.

“To me, the most impressive result was that more than 50% achieved ASAS partial remission after only 12 weeks, despite the caveat of the open-label design,” commented Prof. Baraliakos. Patient-reported symptoms and physical function also improved significantly.

The imaging findings supported the clinical outcomes. Both MRI and PET demonstrated marked, statistically significant reductions in inflammatory lesions, including a significant decline in active osteoblast signal. The inhibition of bone remodelling activity suggests a rapid disease-modifying effect of sonelokimab within affected joints.

The treatment was well tolerated, with no new safety signals identified.

These first clinical data in axSpA suggest that the compact nanobody format of sonelokimab may translate to rapid, high-level ASAS responses and objective improvements on imaging. However, these findings require confirmation in controlled trials.

Baraliakos X, et al. Impact of sonelokimab, a novel IL-17A/F-inhibiting nanobody, on clinical and imaging outcomes in axial spondyloarthritis: first results of a phase 2 study supported by ¹⁸F-NaF PET imaging and MRI. LB0002, EULAR 2026, 3–6 June, London, United Kingdom.