IBI303, a biosimilar to adalimumab, for the treatment of patients with ankylosing spondylitis in China: a randomised, double-blind, phase 3 equivalence trial. (September 2019) - Xu, Huji
Summary: Background: China approved adalimumab for the treatment of ankylosing spondylitis in 2013. However, the cost of the standard dose regimen exceeds ¥15 000 (around US$2250) per month, which is well beyond affordability for most Chinese patients. No biosimilars of adalimumab are available in China; IBI303 is a monoclonal antibody against TNFα that is currently in development. This study aimed to assess the clinical equivalence of IBI303 to adalimumab in patients with ankylosing spondylitis. Methods: This phase 3, multicenter, double-blind, parallel, randomised controlled equivalence trial was done in 20 centers across China. Patients were randomly assigned in a 1:1 ratio to receive either 40 mg of IBI303 or 40 mg of adalimumab as a subcutaneous injection every 2 weeks until week 22. Patients were eligible for inclusion if they were between 18 and 65 years old, fulfilled the 1984 Modified New York Criteria for ankylosing spondylitis, were non-responders, inadequate responders, or intolerant to treatment with NSAIDs for 4 or more weeks, and had active ankylosing spondylitis defined by two or more indicators of disease severity. The investigators, site staff, patients, sponsors, and the contract research organisation were masked to treatment allocation. The primary outcome was the proportion of patients who met the Assessment of SpondyloArthritis international Society (ASAS) Response Criteria for a 20% improvement (ASAS20) at week 24 after treatment. Equivalence was established if the 95% CI of the difference in responses between groups was between −15% and 15%. Efficacy analyses were done in the full analysis population and in the per-protocol population. Safety analyses were done in all randomly assigned patients who received at least one drug dose. This trial is registered with ClinicalTrials.gov, number NCT02893254 . Findings: Between Sept 22, 2016, and May 11, 2018, 438 patients were randomly allocated either to the biosimilar IBI303 group (n=220) or the adalimumab group (n=218). In the full analysis population, 165 (75%) of 220 patients in the IBI303 group (95% CI 68·7–80·6) and 158 (72%) of 218 patients in the adalimumab group (66·0–78·3) reached the primary outcome of ASAS20 at week 24. The difference between the two groups was 2·3% with a 95% CI of −5·9 to 10·6, which fell within the pre-specified equivalence boundaries at week 24 (–15 to 15). In the per-protocol population, 163 (80%) of 203 patients in the IBI303 group reached ASAS20 at week 24 (95% CI 74·1–85·5), compared with 150 (80%) of 188 patients in the adalimumab group (73·3–85·3%). The difference between the groups was 0·6% with a 95% CI of −7·4 to 8·6%, which also fell within the pre-specified equivalence boundaries at week 24. Safety and tolerability profiles were similar between the two groups; 174 (79%) of 220 patients in the IBI303 group and 178 (82%) of 218 patients in the adalimumab group had treatment-emergent adverse events. Interpretation: This trial showed therapeutic equivalence of IBI303 and adalimumab in the treatment of ankylosing spondylitis. The efficacy, safety, and immunogenicity of both drugs are highly similar. IBI303 could be an alternative treatment option for patients with ankylosing spondylitis in China. Funding: Innovent Biologics, National Major Scientific and Technological Special Project for "Significant New Drugs Development".