Shanghai Henlius Biotech has announced the dosing of the first patient in a Phase 2 clinical trial evaluating HLX79, a potential first-in-class human sialidase enzyme therapeutic, in combination with the company's rituximab product HANLIKANG for the treatment of active glomerulonephritis. The milestone represents a significant advancement in addressing a major cause of end-stage renal disease in China.
Novel Glyco-Immunology Approach
HLX79 is developed based on Palleon's EAGLE glycan editing platform and licensed in China by Henlius from Palleon. The therapeutic works through a novel glyco-immunology mechanism by degrading sialic acid to enhance the clearance of two highly pathogenic immune cell populations in autoimmunity: autoreactive memory B cells, which drive inflammation, and M2-like macrophages, which promote fibrosis and organ damage.
Preclinical studies of HLX79 in combination with rituximab demonstrate improved outcomes versus rituximab alone without the risk of cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) associated with CAR T and T cell engagers. HLX79 has demonstrated a favorable safety profile with no dose-limiting toxicities in human clinical trials.
Addressing Significant Unmet Medical Need
End stage renal disease (ESRD), the last stage of chronic kidney disease, is characterized by near-total loss of kidney function, resulting in the need for renal replacement therapy. Patients face high disease severity, complications, and substantial economic burden due to the costs of treatment. China accounts for nearly 30% of global ESRD cases, with approximately 3.5 million patients.
Glomerulonephritis can be classified into primary forms, such as membranous nephropathy and focal segmental glomerulosclerosis, and secondary forms, including lupus nephritis and anti-neutrophilic cytoplasmic antibodies-associated vasculitis, representing the leading cause of ESRD in China.
Trial Design and Objectives
The Phase 2 clinical study (HLX01HLX79-GN201) is a double-blind, randomized, controlled, multi-center trial aimed at evaluating the efficacy, safety, and tolerability of HLX79 in combination with HANLIKANG compared to placebo in patients with active glomerulonephritis, specifically lupus nephritis and membranous nephropathy.
The study consists of two phases. The first phase is a dose-escalation phase, where eligible subjects will receive HLX79 at doses of 10 mg/kg, 20 mg/kg, or 30 mg/kg in combination with HANLIKANG or placebo (375 mg/m²) once a week. The primary objective is to evaluate the safety and tolerability of HLX79 in combination with HANLIKANG compared to placebo in combination with HANLIKANG for the treatment of active glomerulonephritis.
The second phase is an exploratory efficacy phase, where eligible subjects will be assigned in a 2:2:1:1 ratio to receive HLX79 (high dose/low dose) in combination with HANLIKANG (375 mg/m²), HLX79 placebo in combination with HANLIKANG, or HLX79 placebo in combination with HANLIKANG placebo, once a week. The primary objective is to evaluate the clinical efficacy of HLX79 in combination with HANLIKANG, placebo in combination with HANLIKANG, and placebo alone for the treatment of active glomerulonephritis on top of standard therapy.
Secondary objectives include assessing other clinical efficacy, safety, tolerability, pharmacokinetic characteristics, and immunogenicity. Exploratory objectives include evaluating the dynamic changes of potential biomarkers.
Current Treatment Landscape
HANLIKANG, approved in China for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis, remains the only rituximab approved for an autoimmune indication in China. Depleting B cells with targeted antibodies such as rituximab has been approved in multiple markets for the treatment of glomerulonephritis. However, many patients have inadequate response to these drugs.
As of the announcement date, no similar combination therapy has been approved globally, positioning this trial as a potentially groundbreaking development in glomerulonephritis treatment.
