Arrowhead Pharmaceuticals Surges 19% on Successful Phase 3 Results of APOC3-Targeting siRNA Plozasiran in Severe Hypertriglyceridemia

▎Armstrong

On July 22, 2026, Arrowhead Pharmaceuticals announced the top-line data from the Phase 3 SHASTA-3 and SHASTA-4 clinical trials of plozasiran for the treatment of severe hypertriglyceridemia (sHTG).

Arrowhead Pharmaceuticals’ stock price surged 19% on the day, reaching a market capitalization of $12.5 billion.

Plozasiran is Arrowhead's core pipeline.

Plozasiran is a targetedsiRNA of APOC3RNTherapy A effectively reduces serum triglyceride and triglyceride-rich lipoprotein levels through dual lipoprotein lipase-dependent and -independent pathways.

Plozasiran had previously been approved for the treatment of FCS, and has now also achieved success in sHTG.

The number of FCS patients in the United States is approximately 6,500 to 10,000, while sHTG affects more than 3 million patients, among whom about 1 million are classified as high-risk sHTG.

In the newly disclosed SHASTA-3 and SHASTA-4 trials, triglyceride levels decreased by 79% and 81%, respectively, after 12 months of treatment, compared with a 27% decrease in the placebo group. The incidence of at least one episode of acute pancreatitis and the overall incidence were both significantly reduced. Among patients with severe hypertriglyceridemia (sHTG) and triglyceride levels >500 mg/dL, the cumulative incidence of acute pancreatitis was reduced by 78%. In the highest-risk patients with triglyceride levels >880 mg/dL and a history of acute pancreatitis, the incidence of acute pancreatitis was reduced by 100%.

Previously, Olezarsen, an APOC3 ASO novel drug developed by Ionis Pharmaceuticals, demonstrated a maximum reduction of 72% in fasting triglyceride levels (placebo-adjusted) and an 85% reduction in acute pancreatitis events in the Phase 3 CORE and CORE2 clinical trials for severe hypertriglyceridemia (sHTG).

Summary

Ionis’s olezarsen requires monthly administration, whereas Arrowhead’s plozasiran requires dosing only once every three months and has demonstrated superior efficacy data. Plozasiran will become a stronger competitor in the sHTG field. In August 2025, Sanofi licensed the China rights to plozasiran from Visirna, paying$130 million upfront payment, $265 million in milestone payments, and a certain percentage of sales royalties, with a total collaboration value of $395 million.