Etanercept biosimilar(Hanwha Chemical (Thailand) Co. Ltd.)

To evaluate equivalence in efficacy for rheumatoid arthritis (RA) and compare the safety of the biosimilar HD203 with innovator etanercept (ETN) plus methotrexate (MTX) (ClinicalTrials.govNCT01270997).

Patients with active RA received 25 mg HD203 or ETN subcutaneously twice-weekly with MTX for 48 weeks in a phase III, multicentre, randomised, double-blind, parallel-group design. The primary end point was the proportion of patients achieving the American College of Rheumatology 20% response (ACR20) at week 24 for per-protocol study completer set (PPS). Secondary end points included ACR response criteria, ACRn, European League against Rheumatism (EULAR) response, change in Disease Activity Score 28 (DAS28), patient-reported outcomes, safety and immunogenicity.

Of the 294 randomised patients (HD203, n=147; ETN, n=147), 233 comprised the 24-week PPS (n=115 and 118, respectively). ACR20 at week 24 was achieved by 83.48% and 81.36% of PPS patients, respectively, demonstrating equivalent efficacy within predefined margins of ±20% (treatment difference 2.12%, 95% CI −7.65% to 11.89%). Outcomes for secondary end points were consistent with the primary efficacy findings. Groups were comparable for overall incidences of treatment-emergent (all-causality) adverse events (AEs) (HD203 113 (76.9%) vs ETN 114 (78.1%) (p=0.804)), adverse drug reactions, serious AEs and discontinuations due to AEs. Few patients (HD203, n=8; ETN, n=3) tested positive for anti-drug antibodies.

The study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN. HD203 was well tolerated, with safety comparable with ETN in this population of patients with RA.

NCT01270997; Results.

Since the approval of the infliximab biosimilar, CT-P13, by the Korean Ministry of Food & Drug Safety (MFDS) on 23 July 2012,1 biosimilars to treat inflammatory diseases have become available to patients in many countries around the world.2 The European Commission (EC) approved CT-P13 on 10 September 2013,3 and, subsequently, it has been granted marketing authorisation by regulatory agencies in many other countries, including the USA. CT-P13 is now marketed in >70 countries worldwide as Remsima, Inflectra and Flammegis.4 Several other biosimilars of tumour necrosis factor (TNF) inhibitors have also received regulatory approval and are commercially available. HD203 was the first etanercept biosimilar granted marketing authorisation by the Korean MFDS on 11 November 2014 and was marketed as Davictrel in South Korea.5 However, because the facility where it was manufactured was sold, its licence could not be retained and it was withdrawn from the market upon the request of its manufacturer on 30 September 2015. Another etanercept biosimilar, SB4, which received approval by the Korean MFDS on 8 September 2015 and by the EC on 14 January 2016, is marketed as Brenzys in South Korea and as Benepali in the European Union (EU) and in the European Economic Area (EEA) member states of Norway, Iceland and Liechtenstein.5 ,6 SB2, another infliximab biosimilar, was granted marketing authorisation by the Korean MFDS on 4 December 2015 and by the EC on 26 May 2016, and is sold as Renflexis in South Korea and as Flixabi in the EU and EEA member states.5 ,7 In this issue, Bae et al 8 report the results of the phase III clinical trial of HD203 (etanercept biosimilar), Emery and colleagues report the results of the phase III clinical trial of SB4 (etanercept biosimilar)9 and Choe et …