Arrowhead Pharmaceuticals has reported positive results from Part 2 of its Phase 1/2 study of ARO-C3, an investigational RNA interference (RNAi) therapeutic intended for the treatment of patients with IgA Nephropathy (IgAN).
The early-stage study demonstrated an 89% reduction in complement component 3 (C3) levels, highlighting the drug candidate’s potential to target the production of this protein for the treatment of complement-mediated disorders.
Known as AROC3-1001 (NCT05083364), the study is evaluating the safety and efficacy of ARO-C3 in healthy volunteers and patients with complement-mediated renal diseases. In this phase, participants with C3 Glomerulopathy and IgAN received three open-label doses of the therapy.
Arrowhead Pharmaceuticals plans to share additional findings at a medical conference this year.
According to the company, pharmacodynamic results revealed an 85% maximum mean reduction in serum AH50 levels, with sustained reductions above 76% through week 24.
The Wieslab AP assay showed a complete reduction, maintaining an average decrease above 89% from baseline. These data suggest that less frequent dosing, potentially every three months, may be viable in future studies.
Regarding proteinuria, there was an average reduction of 41% in spot urine protein-to-creatinine ratio (UPCR), with some patients experiencing reductions up to 89% by week 24.
Safety assessments indicated that ARO-C3 was generally well-tolerated among IgAN patients, with no serious or severe treatment-emergent adverse events reported. Mild side effects included headache, cough, and nasopharyngitis, with no infections involving encapsulated organisms observed.
Arrowhead Pharmaceuticals chief medical officer and research and development head James Hamilton said: “ARO-C3 has shown potent and consistent results in normal healthy volunteers and now in patients with IgA nephropathy, including up to 89% mean reduction of C3, which led to reductions of 85% in AH50 and 100% in Wieslab AP, both 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.”
