Date: 2016-06-10
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the European League Against Rheumatism Annual European Congress of Rheumatology held in London
Company: Coherus BioSciences (USA - CA) Daiichi Sankyo (Japan) Baxalta (USA - IL)
Product: CHS-0214 (investigational etanercept biosimilar)
Action
mechanism: biosimilar/TNF alpha inhibitor/fusion protein. Etanercept is an anti-tumor necrosis factor (TNF) agent. By blocking TNF, etanercept reduces the inflammation and other symptoms of the diseases.
Disease: rheumatoid arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country: USA
Trial
details: The Phase 3 trial is a randomized, double-blind, active-control, parallel-group, multicenter, global study in subjects with active RA who have demonstrated an inadequate response to methotrexate. The study compared the efficacy, safety, and
immunogenicity of CHS-0214 with etanercept for 24 weeks (Part 1) in patients with moderate/severe RA who had an inadequate response to MTX; then all patients received open-label CHS-0214 for 24 weeks with a final evaluation at
Week 52 (Part 2). (NCT02115750)
Latest
news: * On June 10, 2016, Coherus BioSciences, a pure-play, global biosimilars company with late-stage clinical products, announced the release of study data demonstrating the equivalence of etanercept biosimilar CHS-0214 to Enbrel® (etanercept), the reference product, with respect to efficacy as measured by the primary endpoint, ACR20 at 24 weeks. The study data was released at the European League Against Rheumatism Annual European Congress of Rheumatology held in London, United Kingdom. As a part of the study, the research team conducted a randomized, double-blind, two-part study in patients with moderate to severe rheumatoid arthritis and an inadequate response to methotrexate and who were naïve to biologic therapies. Results of the study demonstrated the equivalence of CHS-0214 to etanercept with respect to efficacy as measured by a primary endpoint. Additionally, secondary endpoints supported equivalence of CHS-0214 to etanercept. There were no clinically meaningful differences between CHS-0214 and etanercept with regard to safety and immunogenicity. * On January. 11, 2016, Coherus BioSciences and Baxalta announced that CHS-0214, a proposed biosimilar of Enbrel® (etanercept), met its primary endpoint in a confirmatory, double-blind, randomized, controlled, two-part clinical study. This ongoing study is evaluating the efficacy and safety of CHS-0214 compared to Enbrel® in patients with moderate-to-severe rheumatoid arthritis that is inadequately controlled with methotrexate alone. The study continues as planned until Week 52. The primary efficacy endpoint was the proportion of subjects achieving ACR20 (20% improvement according to the American College of Rheumatology criteria) at Week 24. The primary endpoint was within the pre-specified margins for demonstrating equivalence of CHS-0214 compared to Enbrel. There were no clinically meaningful differences in the safety and immunogenicity profiles of the two products. This rheumatoid arthritis study is the second of two, large, Phase 3 confirmatory trials intended for inclusion in global marketing applications for CHS-0214. Results for the first Phase 3 study in patients with chronic plaque psoriasis were released in November 2015 and showed that this first study also met its primary endpoints. * On August 18, 2014, Daiichi Sankyo announced the start of the Phase 3 trial of CHS-0214, an investigational etanercept biosimilar, in rheumatoid arthritis (the RApsody trial) in Japan. Daiichi Sankyo is a co-sponsor of this trial, in collaboration with the U.S. company Coherus BioSciences. Daiichi Sankyo is developing CHS-0214 in Japan with the intention to enter the biosimilar market in the near future.
Patients were randomized to 50 mg of CHS-0214 or etanercept subcutaneously QWx24 weeks (Part 1). The primary endpoint was the ACR20 response rate at Week 24. To establish the equivalence of CHS-0214 to etanercept, the 95% confidence interval (CI) of the treatment difference between groups had to be within [–15%, 15%]. Secondary efficacy endpoints (ACR50, ACR 70, and change in DAS28-CRP), safety, and immunogenicity were also evaluated.
In 13 countries, 644 patients on MTX were randomized and received treatment. Baseline characteristics were comparable between treatment groups. At 24 weeks, 512 patients were evaluable for efficacy. The ACR20 response rate was 91.0% (233/256) in the CHS-0214 group and 90.6% (232/256) in the etanercept group. The 95% CI of the treatment difference was [- 4.55, 5.37], which was within the pre-defined equivalence range. The response rates at 24 weeks were 67.6% vs. 63.7% for ACR50 and 38.3% vs. 37.9% for ACR70 in the CHS-0214 and etanercept groups, respectively. Mean (±SD) DAS28-CRP scores were 5.45 (± 1.00) and 5.42 (±1.00) at baseline and decreased to 2.67 (± 1.18) and 2.73 (±1.14) at 24 weeks in the CHS-0214 and etanercept groups, respectively.
Among the 644 patients, adverse events (AEs) occurred in 60.8% and 65.0% of patients in the CHS-0214 and etanercept groups, respectively, including all infections combined in 34.3% and 32.2%, respectively. Investigator-designated treatment-related AEs occurred in 16.4% and 21.9% of patients, respectively, and most commonly included: injection site reactions (2.2% and 13.4%) and all infections combined (7.7% and 5.3%). Treatment-related serious AEs occurred in 3 (0.9%) patients treated with CHS-0214 (cholecystitis, increased blood creatinine phosphokinase, and bronchospasm) and 1 (0.3%) patient treated with etanercept (sepsis). These results demonstrated equivalence of CHS-0214 to etanercept with respect to efficacy as measured by the primary endpoint (ACR20 at Week 24) and other measures (ACR50, ACR70, and DAS28-CRP). CHS-0214 was well tolerated with no clinically meaningful differences to etanercept with regard to safety and immunogenicity.
* On June 23, 2014, Coherus BioSciences announced the start of its Phase 3 trial of CHS-0214, an investigational etanercept biosimilar, in rheumatoid arthritis (RA). The company is also preparing a two part study comparing CHS-0214 to Enbrel® in patients with chronic plaque psoriasis who have not yet received any biologic therapy for any indication (other than insulin or hormones).
