Radiographic Progression Comparable in Patients Receiving Etanercept, Biosimilar

A phase 3 study comparing Samsung Bioepis’ etanercept biosimilar, SB4, to its reference found that SB4 had comparable efficacy—including radiographic progression—to week 52 of treatment in patients with rheumatoid arthritis (RA).

SB4 has been approved by regulatory authorities in the Republic of Korea, the European Union, Australia, and Canada. Pharmacokinetic equivalence between the biosimilar and its reference was demonstrated in an earlier phase 1 study, and equivalent efficacy and comparable safety of the 2 drugs had been demonstrated up to 24 weeks in the phase 3 study. A paper published in Rheumatology provided data up to week 52.

Conducted at 73 centers across 10 countries in Europe, Latin America, and Asia, the study monitored 596 patients with RA who had been diagnosed for 6 months to 15 years and who had taken methotrexate for 6 months or more at the time of screening. Patients were randomized to receive either SB4 (n = 299) or reference etanercept (n = 297) for up to 52 weeks by self-administered injection, with background methotrexate and folic acid.

The primary study endpoint was the proportion of patients achieving a response of ACR20 (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). Efficacy endpoints up to week 52 included ACR20 as well as ACR50 and ACR70 (50% and 70% improvement in the same areas as ACR20); the numeric index of the ACR response, and change in Disease Activity Score 28 scale score (DAS28).

Radiographs of the hands and feet were taken at baseline and week 52, and the images were evaluated by 2 independent readers for changes in the modified total Sharp score (mTSS). Safety assessments included incidents of adverse events (AEs), serious AEs, and anti-drug antibodies (ADAs).

The researchers found that ACR responses of SB4 and reference etanercept were comparable over the time course of the study:

• ACR20 at week 52 was reported in 80.8% of patients in the SB4 arm and 81.5% of patients in the reference etanercept arm
• ACR50 at week 52 was 58.5% and 53.2%, respectively
• ACR70 at week 52 was 37.5% and 31.0%, respectively

Among patients who had ACR responses at week 24, a similar proportion of patients in both treatment arms maintained the level of response at week 52. Among patients who did not have an ACR response at week 24, a similar proportion in both arms achieved ACR responses at week 52.

DAS28 improved by 2.91 from the baseline for the SB4 group and by 2.80 for the reference etanercept group. While radiographic progression from baseline up to week 52 was comparable between the groups, the average change in mTSS from the baseline value was .045 and 0.74 in the SB4 and reference etanercept groups, respectively (95% confidence interval, —0.80 to 0.26).

In terms of safety, 175 patients (58.5%) in the SB4 group and 179 (60.3%) in the reference etanercept group reported at least 1 treatment emergent AE during the study up to week 52: upper respiratory tract infections and increased expression of alanine aminotransferase (ALT) were the most common AEs in the SB4 arm; injection site erythema and increases in ALT were the most commonly reported AEs in the etanercept group. Most AEs were mild to moderate in severity.

Incidence of ADAs was significantly lower in the SB4 arm up to week 52. After week 24, only 1 patient in the SB4 arm developed ADAs. The overall incidence of ADAs to week 52 was 1% for the SB4 arm and 13.2% for the reference etanercept group. The difference in immunogenicity profiles between the 2 treatments did not affect clinical efficacy or safety, the authors note.

The authors conclude that SB4 not only improves clinical and functional outcomes, but also reduces the rate of radiographic progression to an extent that is comparable to that of reference etanercept.