Arrowhead's RNAi Candidate for Kidney Disease Shows Tolerance in Phase 1/2 IgAN Trial

Arrowhead Pharmaceuticals recently reported positive findings from their phase 1/2a study on ARO-C3, an investigational RNA interference (RNAi) candidate aimed at treating complement-mediated diseases. The trial focused on patients with kidney disease, particularly those diagnosed with IgA nephropathy (IgAN), often referred to as Berger’s disease. ARO-C3, an early-stage clinical candidate, is intended to inhibit the production of complement component 3 (C3) in the liver, thereby addressing the underlying pathology of certain renal conditions.

The study, which enrolled 14 patients with complement-mediated renal disease, was structured as an open-label, two-part trial involving both healthy adults and those with specific kidney conditions. The primary objective was to evaluate the safety and tolerability of ARO-C3, as measured by the incidence of adverse events or serious adverse events among participants.

According to Arrowhead, the RNAi therapy was generally well tolerated by participants, including those with IgAN. No severe treatment emergent adverse events (TEAEs) were reported in the IgAN arm of the study through day 169. The most common TEAEs, reported in more than one participant, were headache, cough, and cold-like symptoms. While a complete dataset was not disclosed, additional results are anticipated to be presented at an upcoming medical meeting.

The pharmacodynamic data from the trial revealed significant findings. Participants with IgAN received 400 mg subcutaneous doses of ARO-C3 on days 1, 29, and 113. The treatment led to a sustained reduction in C3 levels of more than 87% through week 24. Additionally, the RNAi candidate was associated with an 85% maximum mean reduction in serum alternative pathway hemolytic assay (AH50) and a 100% maximum mean reduction in Wieslab AP, both of which are indicators of alternative pathway complement activity.

James Hamilton, M.D., Arrowhead’s chief medical officer and head of R&D, emphasized the potential advantages of ARO-C3. He noted that the durable and near-complete inhibition of the alternative complement pathway, achieved through infrequent subcutaneous dosing, could be beneficial for patients. Furthermore, the study showed a 41% reduction in the urine protein-to-creatinine ratio, a surrogate marker of renal injury, indicating potential improvements in kidney function for those with IgAN.

ARO-C3 is one of two assets developed by Arrowhead Pharmaceuticals to target complement-mediated diseases. Despite the promising clinical findings, Arrowhead’s stock saw a minor decline of 4.3%, dropping from $16.56 per share to $16.28. This decrease occurred amid a broader market downturn.

The outcome of the phase 1/2a study underscores the potential of RNA interference technology in addressing complex renal disorders associated with complement dysregulation. As Arrowhead advances its clinical program, further data and insights from ongoing research will be critical in determining the future therapeutic role of ARO-C3 in complement-mediated renal diseases. With additional studies and presentations expected, the medical community eagerly anticipates further developments in this promising area of treatment.