IBI303 Therapeutically Equivalent to Reference Adalimumab in Ankylosing Spondylitis in Phase 3 Study

Results of a phase 3 trial of IBI303, a proposed adalimumab biosimilar referencing Humira, showed that it is therapeutically equivalent in terms of efficacy, safety, and immunogenicity to the originator product, according to a study published in the first issue of The Lancet Rheumatology.

IBI303 is being developed by Innovent Biologics, a China-based biopharmaceutical company, as an alternative treatment option for the treatment of ankylosing spondylitis (AS); it could be the first biosimilar adalimumab product approved in China. The application for the biosimilar was accepted in late 2018 by the National Medical Products Administration (NMPA, formerly known as the China Food and Drug Administration).

China approved adalimumab for AS in 2013, but the cost of brand-name adalimumab exceeds ¥15 000 (around US $2250) per month, which is beyond the means of most patients.

The researchers said this is the first major phase 3 trial of a biosimilar developed in China, as well as the first head-to-head study that compares the efficacy, safety, and immunogenicity of a biosimilar and adalimumab in the treatment of AS.

This phase 3, multicenter, double-blind, parallel, randomized controlled equivalence trial was performed in 20 centers across China. Patients were eligible for inclusion if they met diagnostic criteria for AS; if they were non-responders, inadequate responders, or intolerant to treatment with nonsteroidal anti-inflammatory drugs for 4 or more weeks; and if they had active disease defined by 2 or more indicators of severity.

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. 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.

In total, 438 patients were randomly allocated either to the biosimilar IBI303 group (n = 220) or the reference group (n = 218).

By week 24, initial results showed ASAS20 response rates of 75% and 72.5%, indicating clinical equivalency between IBI303 and the originator product, respectively. 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 reference group (95% CI, 66.0%-78.3%) reached the primary outcome of ASAS20 at week 24. The difference between the 2 groups was 2.3%, with a 95% CI of −5.9% to 10.6%, which fell within the prespecified equivalence boundaries for 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 reference group (73.3%-85.3%). The difference between the groups was 0.6%, with a 95% CI of −7.4% to 8.6%.

There were comparable results in terms of disease activity, improvement of physical functions, spinal mobility, tendonitis, overall patient assessment, and quality of life. In addition, IBI303 was well tolerated, with comparable safety and immunogenicity; 174 (79%) of 220 patients in the IBI303 group and 178 (82%) of 218 patients in the reference group had treatment-emergent adverse events.

The authors said that one limitation of the study is that it lasted for just 24 weeks, so they were unable to observe effects on efficacy and safety that might only appear after long-term use. They did include a pharmacoeconomic analysis of the 2 drugs, the results of which will be released separately.

Reference

Xu H, Li Z, Wu J. IBI303, a biosimilar to adalimumab, for the treatment of patients with ankylosing spondylitis in China: A randomised, double-blind, phase 3 equivalence trial. Lancet Rheumatol. 2019;1(1):e35-43. doi: 10.1016/S2665-9913(19)30013-X.