Shanghai, China, June 17, 2019 – Shanghai Henlius Biotech, Inc. announced new data from the Phase 1 HLX01-RA01 study, which show that HLX01 is bioequivalent to European-Union (EU) sourced MabThera® in rheumatoid arthritis (RA). HLX01 (汉利康®; rituximab injection) was approved by China National Medical Products Administration (NMPA) on February 22, 2019, for the treatment of non-Hodgkin’s’ lymphomas (NHLs). MabThera® is a CD20 targeting antibody that is approved to treat various of hematological malignancies (such as NHLs) and rheumatoid arthritis (RA) in the USA and Europe. In China, MabThera® has been approved for NHL indication only. HLX01 demonstrated pharmacodynamic/ pharmacokinetic (PD/PK) and safety equivalence between HLX01 and EU-rituximab in HLX01-RA01 study. The results from the phase 1 study support the ongoing phase 3 study, evaluating efficacy and safety of HLX01 versus standard-of-care in patients with moderately- to severely- active RA who had inadequate response to disease-modifying anti-rheumatic drugs (DMARSs).
In addition to the HLX01, HLX03-HV01 phase 1 study, which demonstrates that HLX03, its adalimumab biosimilar candidate, is bioequivalent to the subcutaneous injection of the China-sourced Humira®. Humira® is a tumor necrosis factor (TNF) antibody that has been approved in the USA for the treatment of RA, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis. In the HLX03-HV01 study, HLX03 met all the pre-defined PK, safety and immunogenicity endpoints in healthy individuals.The results support the ongoing HLX03-PS03, which is a randomized, double-blind phase 3 study evaluating efficacy and safety of HLX03 versus Humira® in patients with plaque psoriasis (PS).
HLX01-RA01 (NCT03355872) was a randomized, double-blind, multiple dose, parallel-controlled phase 1/2 clinical study of HLX01 compared to EU-rituximab in patients with moderately- to severely-active RA who had inadequate response to disease-modifying anti-rheumatic drugs (DMARSs). A total of 179 patients [HLX01: 88 vs. EU-rituximab: 91] who were randomised at 1:1 ratio to 2 doses (days 1 and 15) either HLX01 or EU-rituximab in the per-protocol analysis completed 24-week evaluation. The area under the concentration-time curve from time 0 to infinity (AUC0-inf) [HLX01: 200753.72 ug*h/mL versus EU-rituximab: 192435.09 ug*h/mL] were similar. The geometric mean ration of AUC0-inf for HLX01 and EU-rituximab was 104.32% and the two-sided 90% confidential intervals (CIs) was (96.49%, 112.80%) within the 80-125% bioequivalence margin. The safety and immunogenicity profiles were similar between HLX01 and EU-rituximab. There was no report on Grade >/= 3 adverse events. There were no significant differences in the proportions of patients with >20% changes in American College of Rheumatology (ACR20) with p=0.5604, ACR50 (p=0.0704) and ACR70 (p=0.1259) at week 24 between HLX01 and EU-rituximab. The changes in disease activity score 28 based on C-reactive protein (DAS28-CRP) scores significantly decreased from baseline in both HLX01 (p<0.0001) and EU-rituximab (p<0.0001) groups with no significant differences between two treatment arms (p=0.6181). The results support the development of HLX01 in an ongoing phase 3 study (HLX01-RA03; NCT03522415) investigating the efficacy and safety of HLX01 combined with methotrexate comparing with standard-of-care in RA.
HLX03-HV01 (NCT03357939) was a randomized, double-blind, single-dose, parallel-controlled phase 1 clinical study of HLX03 compared to CN-adalimumab in healthy male individuals aged 18-45 years with a body mass index of 19-28 kg/m2 and a weight of 50-80 kg. A total of 210 individuals [HLX03: 104 vs. CN-adalimumab: 106] who were randomised at 1:1 ratio to either HLX03 or CN-adalimumab in the per-protocol analysis for PK, the drug maximum serum concentration (Cmax) [HLX03: 3.421 ug/mL vs. CN-adalimumab: 3.345 ug/mL], area under the concentration-time curve from time 0 to the last measurable concentration and to infinity (AUC0-t and AUC0-inf, respectively) [HLX03: 1938.75 ug*h/mL and 2017.61 ug*h/mL vs. CN-adalimumab: 1847.85 ug*h/mL and 1936.47 ug*h/mL] were similar. The two-sided 90% CIs for the geometric mean ratios for all PK parameters were contained within 80-125% bioequivalent margin. The safety and immunogenicity profiles were similar between two treatment groups (p>0.05) and most treatment-emergent adverse events were mild to moderate. The data further support an ongoing phase 3 study (HLX03-PS03; NCT03316781) evaluating the efficacy and safety of HLX03 and CN-adalimumab in the treatment of PS.