CT-P47, a biosimilar candidate to tocilizumab, has demonstrated comparable long-term efficacy and safety to the reference product Actemra in treating rheumatoid arthritis (RA), according to results from a comprehensive phase 3 clinical trial. The findings, published in Clinical Drug Investigation, provide crucial evidence supporting biosimilar switching and may strengthen confidence in cost-effective RA treatment alternatives.
Year-Long Trial Confirms Biosimilar Equivalence
The multicenter, randomized, double-blind study enrolled 444 adult patients aged 18-75 years with moderate to severe RA of at least 24 weeks' duration at 22 centers in Poland. All participants were on stable methotrexate therapy for at least 12 weeks prior to enrollment and were randomized 1:1 to receive either CT-P47 or reference tocilizumab intravenously at 8 mg/kg every 4 weeks.
At week 24, patients receiving CT-P47 continued treatment, while those on Actemra were rerandomized to either continue the reference product or switch to the biosimilar. Among the 444 patients who completed the first treatment phase, 225 continued on CT-P47, 109 continued on Actemra, and 110 switched from Actemra to CT-P47.
Disease activity improvements remained consistent through week 52 across all treatment groups. The mean change from baseline in Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) showed comparable results: CT-P47 (-4.279), Actemra (-4.231), and the switch group (-4.376).
Minimal Disease Progression and Stable Drug Levels
Radiographic progression assessment using the modified total Sharp score revealed minimal joint damage advancement, with more than 81% of patients in all groups showing no radiographic progression over the study period. Serum drug concentration levels remained stable across treatment arms, indicating similar pharmacokinetic profiles.
The incidence of antidrug antibodies was low at less than 5%, and the safety profile remained consistent with historical tocilizumab data. Importantly, no new safety concerns were identified in patients who switched from the originator biologic to the biosimilar.
Self-Administration Success with Autoinjector
A separate phase 3 study (NCT05725434) evaluated CT-P47's subcutaneous self-administration capabilities using an autoinjector device. The single-arm, open-label study included 33 patients with moderate-to-severe RA, with 87.9% completing the entire 12-week study. Most participants were White women (72.7%) with a median 4.8 years since diagnosis.
The study met its primary endpoint when scores for all post-Self-Injection Assessment Questionnaire domains at week 2 exceeded 8, except for "self-confidence" (7.11) and "satisfaction with self-injection" (7.98). The "pain and skin reaction during or after the injection" domain received the highest mean score (9.62), indicating minimal injection-related discomfort.
Clinical improvements were observed with mean DAS28 scores for C-reactive protein and erythrocyte sedimentation rate decreasing from baseline to week 12 by -2.810 and -3.659 standard deviations, respectively. CRP levels dropped from baseline 5.487 to 1.416, while ESR decreased from 35.7 to 8.4 by week 12.
Safety Profile and Market Impact
Treatment-emergent adverse events (TEAEs) occurred in 36.4% of patients in the self-administration study, with 36.4% of these considered drug-related. Leukopenia, neutropenia, and injection site reactions were the most common TEAEs, each affecting 9.1% of patients. Most TEAEs were Grade 1 or 2 in intensity and resolved during the study.
Only two patients discontinued due to TEAEs: one developed a cerebrovascular disorder and another experienced Grade 1 erythema, both considered possibly related to the study drug. No autoinjector malfunctions were reported throughout the study.
Growing Biosimilar Market
The tocilizumab biosimilar landscape is expanding rapidly in both US and European markets. The FDA has approved several tocilizumab biosimilars, including Biogen's Tofidence (tocilizumab-bavi) in September 2023, Fresenius Kabi's Tyenne (tocilizumab-aazg) in March 2024, and Celltrion's CT-P47 (Avtozma; tocilizumab-anoh) in January 2025.
Based on Q3 2024 data, tocilizumab biosimilars have launched with wholesale acquisition cost discounts of 16% for tocilizumab-bavi and 26% for tocilizumab-aazg. The 35% average sales price discount for tocilizumab-aazg compared to the originator is driving modest market growth.
Clinical Implications
These findings address a critical gap in long-term biosimilar switching data, as endorsed by the European League Against Rheumatism (EULAR) for biosimilar use when supported by evidence of comparable efficacy and safety. The results support CT-P47 as a viable biosimilar alternative for RA treatment and provide reassurance regarding the safety and efficacy of switching from the originator biologic.
With rising biologic costs and growing RA prevalence, biosimilars such as CT-P47 may expand treatment access and relieve financial pressure on health systems. The successful demonstration of both intravenous and subcutaneous administration options further enhances treatment flexibility for patients and healthcare providers.
