Infliximab Biosimilar CMAB008 Demonstrates Non-Inferior Efficacy, Safety

The non-inferior efficacy of infliximab biosimilar CMAB008 was proven in a double-blind study and showed comparable early and sustained therapeutic effects and equivalence in patients with rheumatoid arthritis (RA), according to research published in Rheumatology and Therapy.¹ The biosimilar was well tolerated among patients and had comparable safety when compared with the reference drug.

In patients with poor response to methotrexate, adding a biological disease-modifying antirheumatic drug (bDMARD) is recommended. Infliximab has been successfully treating patients with RA since 1999. Now, CMAB008, a recombinant chimeric immunoglobulin G (IgG) 1κ monoclonal antibody, may be another, more affordable, treatment option for this patient population.²

“The high comparability in structure, physicochemical characteristics, and potency of CMAB008 and innovator infliximab are demonstrated,” wrote lead investigator, Hua Ye, associated with the Rheumatology Department at Peking University People’s Hospital, in Beijing, China, and colleagues. “It is theoretically possible that CMAB008 might induce lower anaphylactic reactions due to avoiding expression of the gene for α1, 3-galactosyltransferase of SP2/0 cell.”

A parallel, positive control design, multicenter, phase 3 study was conducted in 31 centers in China between April 2018 and August 2019, in which patients were randomized to receive the biosimilar (3 mg/kg) or reference product (3 mg/kg) concurrently with a stable dose of background methotrexate. Patients received intravenous doses at weeks 0, 2, 6, 14, 22, and 30.

The primary endpoint was achievement of the American College of Rheumatology 20% improvement criteria (ACR20) at week 30. Non-inferiority was determined if the lower limit of the 1-sided 97.5% confidence interval (CI) for the difference was greater than -15%, while equivalence was determined if the 2-sided 95% CI was within ±15% in the analysis. Other endpoints included safety, immunogenicity, pharmacokinetics, and other efficacy assessment parameters. Adverse events were collected throughout the study and pharmacokinetics were assessed through blood samples.

Eligible patients were adults with clinically diagnosed RA, moderate-to-severe active disease, experienced failure with ≥1 type of DMARD, and received methotrexate for ≥3 months with a fixed dose of 7.5 – 15 mg/week for ≥4 weeks.

A total of 191 patients received CMAB008 and 193 received the reference infliximab. Of these patients, 57.6% (n = 110) in the biosimilar cohort and 62.2% (n = 120) in the bio-originator cohort achieved ACR20 at week 30. The exploratory efficacy analysis differences of the rates of patients in both cohorts achieving ACR20 was -4.6% and the lower limit of the 1-sided 97.5% CI was -14.29%. Therefore, CMAB008 was deemed non-inferior to innovator infliximab.

The secondary endpoints, such as safety, efficacy, immunogenicity, and pharmacokinetics, were also highly similar between the drugs. Most (82.4%) patients had at least 1 treatment emergent adverse event (TEAE), with comparable frequencies between the CMAB008 cohort (83.3%) and the infliximab cohort (81.5%). The TEAEs were predominantly categorized as mild to moderate. The frequency of TEAEs leading to discontinuation or dose reduction, severe adverse events, and infusion reaction were similar across treatment groups. The most common adverse reaction was infection.

Limitations noted by investigators included the relatively short study duration and exclusively enrolling Chinese patients.

“The development of biosimilars like CMAB008 provides a tremendous benefit to the large patient population in China with autoimmune and rheumatic diseases, especially inflammatory bowel or RA diseases, whose medical needs are hindered by the high prices of originator drugs,” investigators concluded. “CMAB008 will lead to significant annual cost savings in the treatment of these chronic diseases.”

References

1. ^{Ye H, Liu S, Xu J, et al. Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study. Rheumatol Ther. 2023;10(3):757-773. doi:10.1007/s40744-023-00544-2}
2. ^{Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999;354(9194):1932–9. https://doi.org/10.1016/s0140-6736(99)05246-0}