Arrowhead Pharmaceuticals recently announced positive interim results from a phase 1/2 clinical trial of ARO-C3, an investigational RNA interference (RNAi) therapeutic with potential application in several complement-mediated diseases, including paroxysmal nocturnal hemoglobinuria (PNH).

“ARO-C3 has achieved encouraging results in part 1 of this phase 1/2 clinical study, including a mean reduction of 88% in C3 and 91% in AH50 [a marker of alternative complement pathway hemolytic activity] at the highest dose tested,” said James Hamilton, MD, MBA, chief of discovery and translational medicine at Arrowhead. “These data in healthy volunteers provide us with further confidence as we begin part 2 of the study, which includes patients with various complement-mediated diseases.”

The results, from the ongoing AROC3-1001 trial, showed that ARO-C3 was generally well-tolerated by healthy adult volunteers. No dose-limiting toxicity, serious or severe adverse events, or study discontinuation due to adverse events were reported. Moreover, the investigators did not find clinically relevant laboratory findings or patterns of adverse changes in any clinical laboratory parameters.

The most common adverse events included headache, COVID-19, generally mild injection site reactions, and seasonal allergies.

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“Substantial unmet medical need remains in the treatment of multiple complement-mediated diseases, including IgA nephropathy, C3 glomerulopathy, PNH, and additional renal and hematologic indications, despite the availability of approved complement C5 inhibitors that have significantly improved treatment,” Dr. Hamilton added. “In addition, we believe C3 inhibition has interesting potential, as it is upstream of C5 in the complement cascade.”

The results suggest that the pharmacologic effect of ARO-C3 would be compatible with quarterly or less frequent subcutaneous dose administration.

Given the positive results from part 1, the company plans to initiate dosing in part 2 of AROC3-1001, which will enroll up to 42 adult patients with PNH or complement-mediated renal disease, in the first half of 2023.


Arrowhead announces interim results from ongoing phase 1/2 study of ARO-C3 for treatment of complement mediated diseases. News release. Arrowhead Pharmaceuticals Inc; February 28, 2023.