Phase 3 Study Shows Similarity of LBEC0101 to Reference Etanercept

A newly published study evaluating LG Chem’s proposed biosimilar etanercept in comparison with its reference (Enbrel) found that LBEC0101 had equivalent clinical efficacy and a comparable safety profile to the reference etanercept, and that the proposed biosimilar was well tolerated.

The phase 3, multicenter, randomized, double-blind, parallel-group study was conducted in 48 centers in Japan and 30 centers in the Republic of Korea. Patients included in the study were aged 20 to 75 years, had been diagnosed with rheumatoid arthritis (RA) for 6 months or more, and had active RA despite treatment with methotrexate for 12 weeks or more. Patients were randomized to receive 50 mg of either LBEC0101 or the reference etanercept. In total, 159 patients in the biosimilar arm and 163 patients in the reference arm completed the entire treatment period (up to week 52).

The study found that the least square mean changes in baseline in the disease activity score in a count of 28 joints and erythrocyte sedimentation rate (DAS28-ESR) at week 24, the study’s primary endpoint, was —3.01 (95% CI, –3.198 to –2.820) in the LBEC0101 arm and −2.86 (95% CI, –3.051 to –2.667) in the reference etanercept arm. The estimated between-group difference was –0.15 (95% CI, –0.377 to 0.078), which was within the pre-specified equivalence margin of –0.6 to 0.6.

ACR20 response rates—20% improvement by American College of Rheumatology criteria—were a secondary efficacy endpoint. The percentage of patients achieving ACR20 in the LBEC0101 arm was 93.3% (versus 86.7% in the reference etanercept arm).

In total, 172 patients (92.0%) in the LBEC0101 arm and 173 patients (92.5%) in the reference etanercept arm experienced adverse events (AEs). Serious AEs, including 3 deaths (attributed to circulatory failure, acute heart failure, and acute respiratory distress syndrome) were noted in 31 patients (16.6%) receiving the biosimilar. In patients receiving the reference product, serious AEs, including 1 death (which was not considered related to the study drug), were reported in 20 patients (10.7%).

Injection-site reactions occurred in fewer patients and with a lower frequency in the biosimilar arm (19 patients, 77 events) than in the reference drug arm (64 patients, 438 events). Two patients in the etanercept arm had anti-drug antibodies (ADAs) at baseline. After treatment, 3 patients in the LBEC0101 arm and 18 patients in the reference etanercept arm developed ADAs.

The authors note that the present study was conducted in only Asian nations, and the findings may be limited to the Asian population; therefore, further study is warranted. However, they write, “LBEC0101 is very likely to be insensitive to both intrinsic and extrinsic ethnic factors.” The researchers concluded that the proposed biosimilar is equivalent to its reference in terms of clinical efficacy, and that it was well tolerated and had a comparable safety profile to its reference.

An additional 48-week period following the initial 52-week treatment period is currently underway, and will provide long-term safety, efficacy, and immunogenicity data for LBEC0101.