3 Studies Report on Biosimilar Adalimumab

During the American College of Rheumatology’s Annual Meeting, held in Chicago, Illinois from October 19-24, 2018, various researchers will present findings on the safety, efficacy, and immunogenicity of 3 adalimumab biosimilars.

The first study¹ investigated the clinical equivalence of Boehringer Ingelheim’s BI 695501 (Cyltezo) in a 48-week open-label, multicenter phase 3b extension study (VOLTAIRE-RAext). The trial enrolled 430 adult patients with moderately to severely active rheumatoid arthritis (RA) who could benefit from continuing treatment.

All patients received 40mg of BI 695501 or the reference product in a self-administered pre-filled syringe every 2 weeks. The primary endpoint of the study was proportion of patients with drug-related adverse events (AEs) from the start of VOLTAIRE to the end of 10 weeks’ followup.

The trial comprised 3 arms: 225 patients administered BI 695501 continuously, 102 patients switched from reference adalimumab to BI 695501 at week 24, and 103 patients who continued taking the reference product. In total, 87 patients (20.2%) experienced 1 drug-related AE or less, with a slightly lower proportion in the switch arm (n = 18; 17.6%) compared with patients who took BI 695501 continuously (n = 48; 21.3%) and patients who only took the reference (n = 21; 20.4%). One patient in the BI 695501 continuous-treatment arm experienced AEs that resulted in death, though the study investigator assessed the death as not drug-related.

Overall, the study did not identify new safety or immunogenicity concerns from the original VOLTAIRE study.

A second study² evaluated the effectiveness of a short therapeutic regimen of biosimilar adalimumab (Bsmr-ADL, sold as Exemptia by Zydus Cadila) in ankylosing spondylitis. The observational trial enrolled 50 patients. Each patient was administered 40 mg of subcutaneous biosimilar adalimumab every 2 weeks for 12 weeks.

According to the authors, improvement was quick, clinically significant, and sustained. In total, 80% of patients met criteria for Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) at weeks 12-14. However, 12 patients withdrew from the trial, 1 due to fears about the drug, 4 due to logistical challenges, 5 due to poor response, and 2 for unknown reasons, though none experienced any severe AE.

Overall, the authors noted that the study demonstrated a prolonged benefit of a 12-week regimen with biosimilar adalimumab, although future validation studies are required to confirm the finding.

Finally, the third study³ investigated the efficacy, safety, and immunogenicity of a proposed biosimilar adalimumab, Innovent Biologics’ IBI303, compared with the reference in patients with ankylosing spondylitis.

The trial was a randomized, double-blind, controlled phase 3 study. Patients were randomized to receive IBI303 or the reference product in a 1:1 ratio.

A total of 438 patients were enrolled and randomized (IBI303, n = 220; reference adalimumab, n = 218). The primary endpoint was ASAS20 at week 24. In total, 75% (n = 165) of patients achieved an ASAS20 response in the IBI303 arm, and 72.5% (n = 158) achieved ASAS20 in the reference adalimumab arm. The study's authors further noted that the proposed biosimilar indicated clinical equivalence in terms of efficacy.

The overall incidence of AEs was 79.1% for the IBI303 group, and 81.7 for the reference adalimumab group. The most common AE was an upper respiratory tract infection (24.5% in IBI303 group, and 20.6% in the reference adalimumab group). The authors concluded that IBI303 demonstrated biosimilarity to the reference product in terms of efficacy, safety, and immunogenicity.

References

1. Cohen S, Czeloth N, Lee E, Klimiuk PA, Peter N, Jayadeva G. Biosimilar BI 695501 and adalimumab reference product (RP) have similar efficacy and safety in patients (pts) with moderately-to-severely active rheumatoid arthritis (RA): long-term results from a phase IIIb extension study (VOLTAIRE®-RAext). Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 2522. https://acrabstracts.org/abstract/biosimilar-bi-695501-and-adalimumab-reference-product-rp-have-similar-efficacy-and-safety-in-patients-pts-with-moderately-to-severely-active-rheumatoid-arthritis-ra-long-term-results-from-a-pha/.

2. Chopra A, Khadke N, Saluja M, Kainifard T, Venugopalan A. Prolonged effectiveness of a 12 week regimen of biosimilar adalimumab in indian (Asian) patients suffering from symptomatic acute-chronic ankylosing spondylitis (AS). Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 2617. https://acrabstracts.org/abstract/prolonged-effectiveness-of-a-12-week-regimen-of-biosimilar-adalimumab-in-indian-asian-patients-suffering-from-symptomatic-acute-chronic-ankylosing-spondylitis-as/.

3. Huji X, Zhijun L, Jian W, et al. Similar efficacy and safety of biosimilar candidate IBI303 and reference products of adalimumab in patients with ankylosing spondylitis: results from a randomized, double-blind, phase III Study. Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 2593. https://acrabstracts.org/abstract/similar-efficacy-and-safety-of-biosimilar-candidate-ibi303-and-reference-products-of-adalimumab-in-patients-with-ankylosing-spondylitis-results-from-a-randomized-double-blind-phase-iii-study/.