Rozanolixizumab Has Mixed Phase 2A Results in Severe Fibromyalgia

Rozanolixizumab phase 2A trial design and primary BPI-SF results in fibromyalgia

Rozanolixizumab, a neonatal Fc receptor (FcRn) blocker, did not achieve 2-sided statistical significance on its primary endpoint of Brief Pain Inventory-Short Form (BPI-SF) interference score change at 12 weeks in a phase 2A trial of adults with severe fibromyalgia, though the drug met the trial's pre-specified 1-sided 10% threshold.^¹ The 63-patient trial reported a nominally significant improvement in Revised Fibromyalgia Impact Questionnaire (FIQR) total score at 10 weeks, without corresponding improvement in pain or fatigue numeric rating scores.^¹ Results were published online September 16, 2026, in Lancet Rheumatology.^¹

Rozanolixizumab is a humanised IgG4 monoclonal antibody already approved in multiple geographies for generalised myasthenia gravis, where it reduces pathogenic IgG autoantibody concentration by blocking FcRn-mediated IgG recycling.^¹ This trial is the first prospective randomized study to evaluate an IgG-reducing intervention for fibromyalgia symptoms, testing whether pathogenic IgG autoantibodies contribute to severe disease.^¹ No validated assay for pathogenic autoantibodies exists, so patients were enrolled without biomarker selection.^¹

The phase 2A trial (NCT05643794) enrolled patients aged 18 to 70 years with fibromyalgia per 2016 American College of Rheumatology criteria for a minimum of 6 months, symptoms for at least 2 years, a BPI-SF interference score of six or greater, and a 10-day mean Pain Numeric Rating Scale (NRS) score of 6 or greater and less than 10.^¹ Using a semi-crossover, 3-sequence design, 63 participants across 7 United Kingdom sites were randomized 1:1:1 to rozanolixizumab 560 mg once weekly for 24 weeks, placebo for 12 weeks followed by rozanolixizumab for 12 weeks, or placebo for 24 weeks, all administered by subcutaneous infusion.^¹

The primary endpoint was BPI-SF interference score mean change from baseline after 12 weeks.^¹ This endpoint met the pre-specified 1-sided 10% alpha level, with a least squares mean difference of -0.5 favoring rozanolixizumab versus placebo (80% CI, -1.0 to -0.1; P = .065), but the difference was not significant at a 2-sided 5% alpha level (95% CI, -1.2 to 0.2; P = .13).^¹ The improvement was maintained but remained non-significant at 24 weeks (least squares mean change, -0.5; 95% CI, -1.6 to 0.6; P=.36).^¹

What were Rozanolixizumab secondary endpoints and safety in severe fibromyalgia?

FIQR total score improved significantly from baseline versus placebo at 10 weeks (least squares mean difference, -8.4; 95% CI, -13.8 to -3.0; P = .0026), with significant improvement across all 3 FIQR subdomains: activities (-7.5; 95% CI, -12.5 to -2.4; P = .0039), symptoms (-6.4; 95% CI, -11.5 to -1.3; P = .014), and overall impact (-2.6; 95% CI, -4.2 to -1.0; P = .0012).^¹ Pain NRS and fatigue NRS scores showed no improvement with rozanolixizumab versus placebo at 12 weeks (Pain NRS least squares mean change, 0.0; 95% CI, -0.6 to 0.6; P = .88; Fatigue NRS least squares mean change, -0.3; 95% CI, -0.9 to 0.3; P = .35).^¹

No serious treatment-emergent adverse events (AEs) occurred among participants receiving rozanolixizumab during either treatment period, compared with 3 participants (7%) in the combined placebo group.^¹ Headache was the most common treatment-emergent AE, reported by similar proportions of rozanolixizumab- and placebo-treated participants across the study.^¹ No clinically significant abnormalities in laboratory parameters or vital signs were observed following rozanolixizumab.^¹

Median total IgG reduction from baseline reached approximately 60% by 4 weeks after treatment initiation and was sustained thereafter, according to the study authors.^¹ AEs of special monitoring, including severe or serious headache, were reported by 3 participants receiving rozanolixizumab versus 1 participant receiving placebo, with no events of suspected aseptic meningitis in either group.^¹

Andreas Goebel, PhD, MsC, Professor, Pain Research Institute, University of Liverpool, and colleagues wrote, “Rozanolixizumab did not demonstrate broad efficacy in this severe fibromyalgia population. While there was an improvement in BPI-SF, this was not meaningful at a group level.”^¹ The authors noted inability to select patients with confirmed pathogenic autoantibodies may have contributed to the between-patient heterogeneity observed in treatment response.^¹

The authors said response-predictor biomarkers are needed to determine whether IgG reduction benefits specific patient subsets with severe fibromyalgia.^¹ Other than the recent FDA approval of sublingual cyclobenzaprine, there has been little innovation in pharmacological fibromyalgia treatment for many years, according to the study authors.^¹

References

1. Goebel A, Meisner P, Rydevik G, et al. Efficacy and safety of rozanolixizumab in severe fibromyalgia: a phase 2A randomised, double-blind, placebo-controlled, multicentre trial. Lancet Rheumatol. Published online September 16, 2026. doi:10.1016/S2665-9913(26)00252-3

2. ClinicalTrials.gov. Efficacy and safety of rozanolixizumab in adult participants with fibromyalgia. Identifier: NCT05643794. Accessed September 21, 2026. https://clinicaltrials.gov/study/NCT05643794