BION-1301, an investigational humanized IgG4 monoclonal antibody that blocks APRIL binding to both the BCMA and TACI receptors, is being evaluated in IgA nephropathy.
BION-1301 is a proprietary monoclonal antibody therapeutic targeting APRIL, which is being evaluating for the treatment of IgA nephropathy. Preclinical studies have demonstrated that BION-1301 binds to a specifically defined epitope on APRIL, resulting in complete blockade of APRIL-induced receptor activation. Dosing of BION-1301 in non-human primates led to a significant reduction of blood IgA levels and established a favorable safety profile. Preclinical studies demonstrated that hAPRIL transgenic mice produce rising levels of IgA as well as IgA deposits in the kidney. Administration of mouse anti-human APRIL was shown to reduce levels of IgA in both the serum and the kidney.
The safety and tolerability of BION-1301 was evaluated in a Phase 1 trial in healthy volunteers. In healthy volunteers, BION-1301 was well-tolerated, demonstrated a dose-dependent increase in target engagement as measured by free APRIL levels, and dose-dependently and durably reduced IgA and IgM levels. BION-1301 is currently being evaluated in a Phase 1 clinical trial in patients with IgA nephropathy.
IgA nephropathy is a chronic autoimmune kidney disease. In patients with IgA nephropathy, plasma cells secrete abnormal, galactose-deficient IgA (Gd-IgA1). A critical step in the pathology of IgA nephropathy is the generation of auto-antibodies to Gd-IgA1, leading to the formation of immune complexes, which deposit in the kidney causing inflammation and organ damage. As the disease advances, patients with IgA nephropathy may require dialysis or kidney transplantation. There is no available treatment to reduce production of Gd-IgA1 associated with IgA nephropathy.
APRIL stands for A PRoliferation-Inducing Ligand, a TNF-family ligand involved in regulating plasma cells and normal levels of immunoglobulin production. Specifically, APRIL binds to BCMA and TACI receptors on the surface of plasma cells to stimulate production of IgA, high levels of which are known to promote the disease process in cancers and autoimmune diseases involving plasma cells. Studies have shown high levels of APRIL correlate with poor prognoses in patients with IgA nephropathy.
A Phase 1 clinical trial of BION-1301 in healthy volunteers and patients with IgA nephropathy has been initiated. Parts 1 and 2 in healthy volunteers have been completed and Part 3 of this trial is enrolling patients with IgA Nephropathy. If you are interested in this trial, more information is available here, or please visit ClinicalTrials.gov (NCT03945318) for your nearest site contact and location information.
Additional clinical trials are planned to further evaluate the safety and efficacy of BION-1301 in patients with IgA nephropathy.