Arrowhead Pharmaceuticals’ phase 1/2a study has found the company’s investigational RNA interference (RNAi) candidate was generally well tolerated among 14 patients with kidney disease.
The “select” topline results come from the open-label, two-part trial that enrolled both healthy adult participants and adults with complement-mediated renal disease. The main goal of the study was to assess safety and tolerability of the asset, known as ARO-C3, with the trial’s primary endpoint measuring the number of participants with adverse events or serious adverse events.
ARO-C3 was generally well tolerated among the cohort of patients with IgA nephropathy (IgAN)—also known as Berger’s disease, according to a March 10 release from the California company.
No severe treatment emergent adverse events (TEAEs) were reported through day 169 for the IgAN arm, according to Arrowhead. The only TEAEs reported in more than one participant were headache, cough and cold symptoms, the company said. A full dataset wasn’t shared, with additional results expected to be presented at a medical meeting this year.
Arrowhead also shared data on pharmacodynamic effects from the 14 participants with IgA, who received 400 mg subcutaneous doses of ARO-C3 on days 1, 29 and 113.
ARO-C3—designed to reduce liver production of complement component 3 (C3)—was tied to a greater-than-87% mean sustained reduction in C3 through week 24, according to Arrowhead.
The RNAi asset was also linked to an 85% maximum mean reduction in serum alternative pathway hemolytic assay (AH50), and a 100% maximum mean reduction in Wieslab AP (alternative pathway), according to the biotech. Both are markers of alternative pathway complement activity.
“Such durable and near complete inhibition of the alternative complement pathway achieved with infrequent subcutaneous dose administration may be advantageous,” Arrowhead chief medical officer and R&D head James Hamilton, M.D., said in the release. “In addition, proteinuria, a surrogate marker of renal injury in IgAN, improved with a 41% reduction in spot [urine protein-to-creatinine ratio].”
ARO-C3 is one of Arrowhead’s earliest-stage clinical candidates and is one of two assets designed to target complement-mediated diseases.
Arrowhead’s stock has dropped slightly since market open, slipping 4.3% from $16.56 per share to $16.28 as of 10:30 a.m. The decline came amid a market-wide selloff on Monday.