The study concludes that the VOLTAIRE-RA study showed that the biosimilar Cyltezo and reference Humira are highly similar, and that switching from the reference to the biosimilar had no impact on efficacy, safety, or immunogenicity.
Research has already demonstrated the structural similarity and comparable functionality of Boehringer Ingelheim’s FDA-approved biosimilar adalimumab (Cyltezo), referencing Humira, and the VOLTAIRE-PK study established 3-way pharmacokinetic similarity between Cyltezo and both EU- and US-approved Humira. Newly released data from the 58-week VOLTAIRE-RA trial (48-week data from which were previously announced in an abstract), according to findings published in Annals of the Rheumatic Diseases, demonstrates that switching from the reference drug to the biosimilar had no impact on efficacy, safety, or immunogenicity.
VOLTAIRE-RA was a randomized, double-blind, parallel-arm equivalence trial of Cyltezo and US-sourced Humira in 15 sites in 14 countries. Patients (n = 645) with moderate to severe rheumatoid arthritis (RA) who were stable on methotrexate (and had not been previously exposed to adalimumab or to more than 1 other biologic) were randomized to receive 40-mg subcutaneous doses of either the biosimilar (n = 324) or the reference adalimumab (n = 321) by pre-filled syringe once every 2 weeks for 24 weeks.
Continuing patients who received the reference adalimumab were then re-randomized at week 24 to continue on the reference (n = 148) or to switch to the biosimilar (n = 147), while those who had been receiving the biosimilar (n = 298) continued with the existing treatment. At week 48, qualifying patients (n = 559) could enter an open-label extension in which they received the biosimilar. Those who did not enter the extension were followed up at week 58 for safety.
The study’s coprimary endpoints were the percentage of patients meeting the American College of Rheumatology’s criteria for a 20% improvement (ACR20) at week 12 (requested by FDA) and week 24 (requested by European Medicines Association [EMA]). Equivalence was demonstrated when the difference in ACR20 response rates (biosimilar minus reference) was within —12% and 15% (90% CI, week 12 per FDA) and within −15% and 15% (95% CI, week 24 per EMA).
The researchers found that the difference in the proportion of patients achieving an ACR20 response was within the prespecified interval at week 12 (90% CI, −0.9 to 12.7) and week 24 (95% CI, −3.4 to 12.5). At week 48, the 3 treatment groups generated at re-randomization had similar proportions of patients who achieved ACR20, 50, and 70 response rates.
For all patients who did not enter the open-label extension, the safety follow-up at week 58 showed that the proportion of patients with drug-related adverse events (AEs) was similar between the treatment groups.
The number of patients who had at least 1 drug-related AE from day 1 to week 58, and from week 24 to 58, respectively, were the following among the treatment groups:
Among serious AEs, infections and infestations were the most commonly reported (0.6% for the biosimilar and 4.0% for the reference). No deaths were reported during the study.
In terms of immunogenicity, 50.2% of patients were positive for anti-drug antibodies (ADAs) at any time point up to week 24, with similar frequencies between the biosimilar group (47.4%) and the reference group (53.0%). ADA titers at week 24 and neutralizing antibody frequencies up to week 24 were also similar between groups, and were not altered by a transition from the reference to the biosimilar. Similar immunogenicity was observed in all re-randomized groups up to week 48.
The study concludes that the VOLTAIRE-RA study showed that the biosimilar Cyltezo and reference Humira are highly similar, and that switching from the reference to the biosimilar had no impact on efficacy, safety, or immunogenicity. These data, together with analytical and phase 1 data, suggest that the 2 products are therapeutically equivalent, say the authors.
Cohen SB, Alonso-Ruiz A, Klimiuk PA, et al. Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study. [Published online March 7, 2018.] Ann Rheum Dis. doi:10.1136/annrheumdis-2017-212245.