James Hamilton on RNA interference
From AHA 2019: RNA Interference Targeting Apolipoprotein C-III — Dr James Hamilton · · Radcliffe Cardiology
“A single dose of Arrowhead's RNAi therapeutic can silence the apoC-III gene by up to 94%, resulting in a 60 to 70% reduction in triglyceride levels, demonstrating deep and durable effects.”
On , James Hamilton, Chief Medical Officer and Head of R&D at ARROWHEAD PHARMACEUTICAL INC, spoke about RNA interference during AHA 2019: RNA Interference Targeting Apolipoprotein C-III — Dr James Hamilton on Radcliffe Cardiology.
About James Hamilton
During Arrowhead Pharmaceuticals' fiscal year 2025 earnings call on November 26, 2025, James Hamilton discussed the company's development programs. He noted that the SHASTA 3 and 4 trials were powered on the basis of triglyceride reduction as the primary endpoint, not specifically for pancreatitis. Hamilton stated that the SHASTA 5 trial was designed with a primary endpoint of acute pancreatitis and had been modified to include a more generalizable population of patients with persistent chylomicronemia and a history of pancreatitis, with inclusion criteria allowing triglycerides up to 880 mg/dL and requiring either non-HDL cholesterol of 100 mg/dL or LDL greater than 70 mg/dL. He said the company anticipates completing the primary portions of these studies in mid-2026, with topline data expected in the third quarter of 2026, and if successful, plans to make regulatory submissions before the end of 2026. In earlier presentations from 2019 and 2020, Hamilton described Arrowhead's RNA interference therapeutics targeting the liver proteins apolipoprotein C-III (APOC3) and angiopoietin-like 3 (ANGPTL3). He stated that a single dose of the APOC3-targeting compound reduced APOC3 blood levels by up to 94% and triglycerides by 60 to 70%, with effects lasting up to 16 weeks. For the ANGPTL3-targeting compound, he reported reductions of about 80% in ANGPTL3, 60 to 70% in triglycerides, and 30% in LDL cholesterol after a single dose. Hamilton characterized the drugs as having a favorable safety and tolerability profile in healthy volunteers, supporting further development, and noted that subcutaneous dosing could potentially be as infrequent as every three to six months.