SB5 Shows Equivalent Response Rate to Humira in Patients With Rheumatoid Arthritis

A phase 3 trial of SB5, a proposed biosimilar to rheumatoid arthritis (RA) drug adalimumab (AbbVie’s Humira), showed that SB5 was equivalent to its reference with respect to the American College of Rheumatology 20% improvement criteria (ACR20). The results were reported in the January 2018 issue of Arthritis & Rheumatology by Michael E. Weinblatt, MD, and colleagues. The study was funded by Samsung Bioepis, developer of SB5 (brand name, Imraldi).

The double-blind, parallel-group study of patients with moderately to severely active RA despite treatment with methotrexate included 542 patients who were randomized 1:1 to receive SB5 (269 patients) or reference adalimumab (273 patients) at a dosage of 40 mg subcutaneously every other week. The primary efficacy endpoint was response rate based on the ACR20 at week 24. The study also evaluated endpoints of efficacy, pharmacokinetics (PK), safety, and immunogenicity assessments. The study was conducted from May 2014 through May 2015 in 7 countries (Bosnia and Herzegovina, Bulgaria, Czech Republic, Lithuania, Poland, Republic of Korea, and Ukraine).

The investigators found:

• Equivalent efficacy between SB5 and reference adalimumab with regard to ACR20 response rate—the primary endpoint—and the ACR20 time-response model showed equivalent efficacy over multiple time points assessed during the study.
• Secondary endpoints, such as the ACR50 and ACR70 response rates and the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) and European League Against Rheumatism (EULAR) responses were comparable between the SB5 and the reference adalimumab groups.
• The safety profile of SB5 was also comparable to that of the reference adalimumab, with similar incidence rates of treatment-emergent adverse events (TEAEs), serious TEAEs, serious infections, and injection-site reactions. Fewer patients in the SB5 group than in the reference adalimumab group experienced TEAEs leading to treatment discontinuation, and most of these TEAES were considered to be related to the study drug, the researchers note.
• Comparable immunogenicity with respect to the incidence of antidrug antibodies was also shown. ACR responses at week 24 in the SB5 group were lower in anti-drug antibody- (ADA) positive patients compared with ADA-negative patients, but there was a weaker correlation between the presence of ADAs and clinical efficacy in the reference adalimumab treatment group, which the investigators attribute to the small number of ADA-positive patients and a fluctuation in the ACR responses.

The researchers explain that their study was conducted to demonstrate equivalence in terms of clinical efficacy in a representative study population, and was designed to be sensitive enough to detect potential differences in efficacy between SB5 and the reference adalimumab in accordance with European Medicines Agency guidelines. It was not focused on demonstrating efficacy per se, because the efficacy of adalimumab in RA has already been well established. “Examining the efficacy of SB5 in comparison with reference [adalimumab] in RA is an appropriate choice for demonstrating similarity in efficacy between the 2 products,” they note, concluding that their findings showed equivalent efficacy between SB5 and the reference product as demonstrated by the ACR20 response rates and other secondary efficacy endpoints at week 24. “The study demonstrates that SB5 was well tolerated and possessed PK, safety, and immunogenicity profiles comparable to those of the reference [adalimumab].”