Pharmacokinetics, safety, and immunogenicity of HLX03, an adalimumab biosimilar, compared with reference biologic in healthy Chinese male volunteers: Results of a randomized, double‐blind, parallel‐controlled, phase 1 study

Abstract

The primary objective of this randomized, double‐blind, parallel‐controlled study (from December 2016 to October 2018) was to evaluate pharmacokinetic (PK) equivalence of adalimumab biosimilar HLX03 and reference adalimumab in healthy volunteers, and to assess safety, and immunogenicity of HLX03. The primary PK endpoints were maximum observed plasma concentration ( C max ) and area under the concentration curve from time zero to the last quantifiable concentration (AUC 0–t ). Equivalence was determined if the 90% confidence interval (CI) of geometric least square mean ratio between the two treatment groups were within the predefined range of 80%–125%. Safety and immunogenicity were monitored during the study. Healthy Chinese males ( N = 220) were randomized 1:1 to receive a single subcutaneous 40 mg dose of HLX03 or China (CN)‐sourced adalimumab. The ratios of the geometric mean of C max and AUC 0–t were 102.2% and 105.7%, respectively, with corresponding 90% CIs falling in the predefined margins, which demonstrated PK equivalence between HLX03 and CN‐adalimumab. The incidence of treatment‐emergent adverse events (TEAEs) was similar in the two groups (73.8% and 66.0% in the HLX03 and CN‐adalimumab groups, respectively). Grade 3–4 TEAEs were reported in 7.5% and 5.7% of participants, respectively. The incidences of participants with antidrug antibodies (HLX03: 96.2%; CN‐adalimumab: 93.4%) or neutralizing antibodies (HLX03: 40.6%, CN‐adalimumab: 41.4%) were comparable between groups. This study demonstrated PK bioequivalence between HLX03 and CN‐adalimumab, with similar safety and immunogenicity profiles. These data support further clinical development of HLX03 as an adalimumab biosimilar.

Biosimilar monoclonal antibodies in China: A patent review

“…With these improving techniques and scientific studies, the similarity of the marketed anti-tumor biosimilars with their reference drugs in terms of clinical efficacy, safety, and immunogenicity has been confirmed in the results of different registered clinical trials and clinical studies [ 25–27 , 29 , 38–41 , 81 , 82 , 114 , 115 ].…”

“…Listed in 2019, HS016 (Hisun) has similar safety, efficacy, and immunogenicity according to clinical trials (CTR20160450, CTR20160398, http://www.cde.org.cn ) and is the first biosimilar approved for all indications of Humira® [ 25–27 ]. The clinical trial reports of IBI303 (Innoventbio, CTR20160219, CTR20160628, CTR20160687, http://www.cde.org.cn )[ 28 ] and HLX03 (Henlius, CTR20160930, CTR20171123, http://www.cde.org.cn )[ 29 ] supported the clinical development of two biosimilars.…”

A novel therapeutic vaccine targeting the soluble TNFα receptor II to limit the progression of cardiovascular disease: AtheroVax™

“…Humera (adalimumab) is a recombinant human monoclonal antibody that binds TNF-α administered as a 40 mg dose SQ. The elimination half-life was 231.9 h in adult male healthy volunteers with a 71 percent coefficient of variation ( 21 ). This study identified 93.4 percent of patients with ADA by day 70 and 41.4 percent of patients with Nabs by day 70.…”