HLX01 ( rituximab injection) is the first monoclonal antibody (mAb) biosimilar independently developed by Henlius and the first-ever China-manufactured biosimilar approved by the NMPA in accordance with the Technical Guidelines for the Development and Evaluation of Biosimilars (Tentative). It has been approved for the treatment of Non-hodgkin's lymphoma and leukemia, covering all the indications approved for the rituximab originator in Chinese Mainland. Since the rituximab originator has not been approved for RA in China, Henlius has adopted a differentiated strategy to fully develop the potential of HLX01 (rituximab injection) in RA and to benefit a broader patient population. In December 2021, the National Medical Products Administration (NMPA) has accepted the New Drug Application (NDA) for a new indication of HLX01 to treat RA. 

Details of the publications of HLX01-RA03:

● Title

Efficacy and Safety of HLX01 in Patients with Moderately to Severely Active Rheumatoid Arthritis Who Had Inadequate Responses to Methotrexate: Results of a Randomised, Double-blind, Placebo-controlled Phase 3 Study

● Leading PI

Xiaofeng Zeng, MD, PhD, Peking Union Medical College Hospital

● Form

Abstract and Poster 

● Abstract No.

2099

● Study Design

HLX01-RA03 is a randomised, double-blind, placebo-controlled, phase 3 study aimed to evaluate the efficacy and safety of HLX01 (rituximab injection) in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis (RA) who have had MTX-inadequate response (MTX-IR). Eligible patients were randomised 2:1 to receive 1000 mg HLX01 or placebo on day 1 and day 15 by intravenous infusion. Patients were retreated with or switched to receive (if initially assigned to placebo) 1000 mg HLX01 on day 169 (the first day of week 24) and day 183. A stable dose of MTX was administered to all patients during the study. Patients with inadequate responses at week 16 and week 20 could receive rescue treatments. The primary endpoint of the study is the proportion of patients who met American College of Rheumatology 20 (ACR20) criteria at week 24.

● Results

1) Efficacy

a) Primary endpoint

275 patients were enrolled (HLX01 group, n = 183; Placebo group, n = 92) in this study. A significantly greater proportion of patients achieved ACR20 response in the HLX01 group compared with the placebo group in the ITT population at week 24 (60.7% vs 35.9%; odds ratio [OR], 2.756 [95% CI 1.640, 4.632]; P < 0.001).

b) Secondary endpoints

The secondary efficacy endpoints include proportions of patients achieving ACR20/50/70, disease activity score measured by 28 joints (DAS28) based on C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), improvement in physical function assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI), and so on. The results demonstrated that the secondary efficacy endpoints were also significantly improved in HLX01 group compared with placebo group.

2) Safety

The overall incidence of treatment emergent adverse events (TEAEs), adverse drug reactions (ADRs), and TEAEs leading to drug discontinuation were similar among treatment groups.

● Conclusion

HLX01 plus MTX showed significantly improved clinical outcomes and comparable safety profiles compared with placebo in Chinese patients with moderate to severe active RA who had inadequate responses to MTX, demonstrating HLX01 in combination with MTX as a well-tolerated, safe, and efficient treatment option.