Roche Submits sBLA for CD20 Monoclonal Antibody Gazyva (Obinutuzumab) in Systemic Lupus Erythematosus
Genentech
Pharmaceutical R&D Manufacturer
Gazyva is a humanized monoclonal antibody designed with a Type II anti-CD20 fragment (for direct induction of B-cell apoptosis) and a glycoengineered Fc fragment (to increase binding affinity and enhance antibody-dependent cellular cytotoxicity).The drug has been approved by the US and EU for the treatment of adult lupus nephritis.. In addition, Gazyva has been approved in 100 countries for the treatment of various hematologic malignancies.
ALLEGORY Study (NCT04963296) is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial designed to evaluate the efficacy and safety of Gazyva in combination with standard therapy for the treatment of adult patients with active systemic lupus erythematosus (SLE). The study enrolled approximately 300 patients, who were randomly assigned in a 1:1 ratio to receive either Gazyva or placebo. The treatment period lasted up to 52 weeks, followed by an open-label extension phase lasting up to 104 weeks. The primary endpoint was the proportion of patients achieving the SLE Responder Index 4 (SRI-4) at Week 52.
The research results show that,At week 52, the SRI-4 response rate (at least a 4-point improvement in score) was 76.7% in the Gazyva plus standard therapy group, significantly higher than 53.5% in the placebo plus standard therapy group (adjusted difference 23.1%, 95% CI: 12.5-33.6, p<0.001).. In terms of safety,The safety profile of Gazyva was consistent with the known information, and no new safety signals were identified.Moreover, Gazyva outperformed the placebo across all key secondary endpoints and achieved other secondary endpoints.
Research shows,Gazyva Combined with Standard Treatment Significantly Reduces the Risk of Recurrence Before Week 52(Hazard ratio 0.58, 95% CI: 0.40-0.82, p=0.002), and recurrence may lead to permanent organ damage; the median time to first recurrence in this group could not be estimated.
In terms of remission rate,The proportion of patients in the Gazyva group achieving systemic lupus erythematosus remission (DORIS) at week 52 was 33.8%, more than double that of the placebo group (13.8%).(Adjusted difference 19.9%, 95% CI: 10.6-29.2); the proportion achieving Lupus Low Disease Activity State (LLDAS) was 57.6%, more than twice as high as that in the placebo group (25.0%) (adjusted difference 32.6%, 95% CI: 22.3-43.0).
Phase IIIALLEGORY Study Data Submitted to European Medicines Agency. As one of the four positive Phase III studies of Gazyva in the field of immune-mediated diseases, the other three are the REGENCY study for lupus nephritis, the INShore study for idiopathic nephrotic syndrome, and the MAJESTY study for primary membranous nephropathy. This evidence strongly supports the therapeutic potential of Gazyva across various immune-mediated diseases.
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