Arrowhead Pharmaceuticals Announces Topline Results from Part 2 of Phase 1/2 Study of ARO-C3 in Patients with IgA Nephropathy
March 10, 2025
- ARO-C3 achieved deep and sustained reductions in alternative pathway complement activity and proteinuria
- Mean sustained reductions in C3 of =87%, AH50 of =76%, Wieslab AP of =89% through week 24
- Mean reduction in spot urine protein-to-creatinine ratio (UPCR) of 41% by week 24
PASADENA, Calif.--(BUSINESS WIRE)--Mar. 10, 2025-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced topline results from Part 2 of a Phase 1/2 clinical study of ARO-C3, the company’s investigational RNA interference (RNAi) therapeutic designed to reduce liver production of complement component 3 (C3) as a potential therapy for various complement mediated diseases. The company plans to present additional results at a medical meeting in 2025.
Select Phase 1/2 Study Results
Patients with IgA nephropathy (IgAN) (n=14) received subcutaneous doses of ARO-C3 (400 mg) on Days 1, 29, and 113 and were followed through Day 169
Pharmacodynamic effects
Maximum mean reduction in C3 of 89% and mean sustained reduction of greater than 87% from baseline through week 24
Maximum mean reduction in serum AH50 (alternative pathway hemolytic assay) of 85% and mean sustained reduction greater than 76% from baseline through week 24
Maximum mean reduction in Wieslab AP (alternative pathway) of 100% and mean sustained reduction greater than 89% from baseline through week 24
Duration of effect supportive of once every three month or less frequent subcutaneous dosing in later stage studies
Effects on proteinuria
Mean reduction in spot UPCR of 41% and maximum individual reduction of 89% from baseline by week 24
Safety and Tolerability
ARO-C3 was generally well-tolerated in patients with IgAN
No serious or severe treatment emergent adverse events (TEAE) and no TEAEs that led to study or study drug discontinuation
The only TEAEs reported in more than 1 subject were headache, cough, and nasopharyngitis
No infections with encapsulated organisms
“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 complement component 3 (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,” said James Hamilton, M.D., MBA, Chief Medical Officer and Head of R&D. “In addition, proteinuria, a surrogate marker of renal injury in IgAN, improved with a 41% reduction in spot UPCR. We look forward to sharing more data from the Phase 1/2 clinical study of ARO-C3 at an upcoming medical meeting in 2025.”