Povetacicept Shows Promise for IgAN Treatment

Researchers led by James Tumlin presented updated data based on longer follow-up from the RUBY-3 phase 1b/2a study of povetacicept in an abstract at the International Society of Nephrology  World Congress of Nephrology 2024. Initial results of RUBY-3 found that povetacicept 80 mg given subcutaneously once every 4 weeks showed good tolerability with multiple dosing and promising reductions in urine protein-to-creatinine ratio (UPCR) and galactose-deficient IgA1 (Gd-IgA1) in study participants with immunoglobulin A nephropathy (IgAN).

RUBY-3 participants are aged ≥18 years with biopsy-confirmed IgAN, lupus nephritis, and primary membranous nephropathy, on maximally tolerated angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy, and with well-controlled blood pressure and disease-specific immunosuppressive therapy as applicable. They receive povetacicept 80 or 240 mg subcutaneously once every 4 weeks. The primary objective of the study is safety; efficacy is among the secondary objectives.

As of December 1, 2023, 12 participants were enrolled and receiving povetacicept 80 mg; seven (58%) of them received ≥24 weeks of treatment. Povetacicept has been well-tolerated, with no incidences of severe hypogammaglobulinemia (IgG <3 g/L) or severe infections. Povetacicept 80 mg was associated with a UPCR reduction of 52.6% at 24 weeks (n=7) and with reductions in Gd-IgA1, stable renal function (based on estimated glomerular filtration rate), and pharmacodynamically expected decreases in immunoglobulin levels.

In sum, povetacicept is well-tolerated with multiple dosing and shows promising activity in IgAN. These results support further study of povetacicept in IgAN and other glomerulonephritis and autoantibody-associated diseases.

Source: KI Reports