The authors write that these data add to the totality of the evidence supporting the biosimilarity of the biosimilar infliximab with its reference.
Sandoz’s infliximab biosimilar, GP1111, was approved in the European Union under the name Zessly in May 2018. Approval of the drug was based on a data package that included findings from the 30-week phase 3 REFLECTIONS B537-02 study in patients with rheumatoid arthritis (RA). Now, investigators have published a new paper that provides data on the biosimilar up to week 54, which includes information on patients who switched to the biosimilar from the reference.
As previously reported, 650 patients were randomized to receive either the biosimilar (n = 324) or the reference (n = 326). At week 30, 566 patients who completed the first treatment phase entered the second phase. Among these patients, 280 continued to receive the biosimilar, and 286 patients treated with the reference in the first study phase were rerandomized to either continue the reference (n = 143) or switch to the biosimilar (n = 143). In total, 89.4% of patients completed the 54 weeks of treatment.
At week 30, as reported elsewhere, response rates as measured by American College of Rheumatology (ACR) criteria for 20%, 50%, and 70% improvement were similar between patients receiving the biosimilar and those receiving the reference. At week 54, ACR response rates were as follows for the biosimilar-only, the reference-only, and the switch groups:
At week 30, Disease Activity Scores in a count of 28 joints with C-reactive protein (DAS28-CRP) were the same—3.8—in the biosimilar and reference groups. At week 54, the mean change in DAS28-CRP from week zero and the mean DAS28-CRP values were as follows for the biosimilar-only group, the reference-only group, and the switch group:
At week 30, mean changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) were similar between groups. Mean changes in HAQ-DI from week 30 to 54 were as follows for the 3 groups:
The percentages of patients who had anti-drug antibodies (ADAs) between week 30 and week 54 were as follows for the 3 groups:
The incidence of treatment-emergent adverse events (TEAEs) and discontinuations related to TEAEs were comparable across groups, with the most frequently reported AEs being infusion-related reactions, nasopharyngitis, and exacerbation of RA. No clinically meaningful differences were present among groups for AEs of special interest, such as infusion-related reactions or hypersensitivity.
The authors conclude that these data add to the totality of the evidence supporting the biosimilarity of the biosimilar infliximab with its reference. “These data provide additional reassurance to physicians who may want to see additional data compared with that required by regulatory agencies, and for those who have concerns about the potential for increased immunogenicity after switching from a reference medicine to a biosimilar,” they write.
While Zessly is available in the European Union, the same biosimilar infliximab product is approved in the United States (where it is known as Ixifi). However, Pfizer, which owns the US rights to the product, has indicated that it does not plan to launch the biosimilar in the US market; at the time of Ixifi’s FDA approval in 2017, a Pfizer representative told The Center for Biosimilars® that the company would continue to focus on marketing its first infliximab biosimilar, Inflectra, in the US market, and that the approval of Ixifi will not impact its strategy with Inflectra.
Alten R, Batko B, Hala T, et al. Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogencity from week 30 to week 54. RMD Open. 2019;5:e000876. doi: 10.1136/rmdopen-2018-000876.