Phase 1 PK Study of SB5 Shows Equivalence to Reference Adalimumab

A study published in the July 3, 2017, issue of the Journal of Clinical Pharmacy and Therapeutics found that SB5, a proposed biosimilar to rheumatoid arthritis (RA) drug adalimumab (AbbVie’s Humira) had pharmacokinetic (PK) equivalence to both European-sourced (EU-ADL) and US-sourced adalimumab (US-ADL), and was also well-tolerated and had a similar safety and immunogenicity profile to both EU- and US- sourced adalimumab. The study was supported by Samsung Bioepis Co., Ltd., the developer of SB5.

Donghoon Shin, MD, PhD, of Samsung Bioepis Co, Ltd., Incheon, Korea, and colleagues conducted the phase 1, single-blind trial in 189 healthy volunteers. The subjects were randomly selected to receive a single 40-mg dose of SB5, EU-ADL, or US-ADL that was administered via pre-filled syringe by subcutaneous injection. Patients’ baseline characteristics and demographics were comparable among the 3 groups; the mean age of the study’s subjects was 39.5 years, and the majority of subjects were male and Caucasian.

The study’s subjects were evaluated for 71 days after receiving the dose of either SB5, EU-ADL, or US-ADL. Serum adalimumab concentrations were measured using enzyme-linked immunosorbent assay (ELISA) testing; PK parameters were calculated based on actual sampling times relative to dosing. Non-compartmental analysis methods and equivalence were determined using pre-defined equivalence margins of 0.8 to 1.25.

Mean values of area under the concentration-time curve from time 0 to infinity (AUC_inf), maximum serum concentration (C_max), and AUC from time 0 to the last quantifiable concentration (AUC_last) were similar between the 3 groups. The 90% confidence interval for these parameters was within the pre-defined equivalence margins for all pair-wise comparisons, the authors concluded.

There were no discontinuations from the study because of treatment-emergent adverse events (TEAEs), and no deaths were reported. The number and type of TEAEs were comparable among the 3 groups, and all were considered mild to moderate. The incidence of study subjects developing antidrug antibodies (ADAs) and the overall incidence of neutralizing antibodies (NAb) were comparable across the 3 groups.

Sixteen patients were excluded from the analysis because they did not satisfy the criteria to be included in the PK analysis (eg, there were insufficient drug concentrations for PK estimations to be made). All of these subjects had positive ADA results on post-dose day 15 and relatively high titers of ADA. The results of a separate sensitivity analysis conducted on all study subjects, including these 16 subjects, were consistent with the primary analysis, and the equivalence criteria were met for all pair-wise comparisons, confirming that SB5 EU-ADL, and US-ADL are all bioequivalent.

The study's authors note that a pivotal phase 3 study of SB5 has already been completed, and that it demonstrated the equivalence of SB5 to EU-ADL in terms of the ACR20 response (

or the American College of Rheumatology 20% improvement in tender and swollen joint counts; patient assessments of pain, global disease activity, and physical function; physician global assessment of disease activity; and acute phase reactant

) at week 24 in patients who have moderate to severe RA despite receiving methotrexate therapy.