Arrowhead Pharmaceuticals announced on July 22 topline data from two late-stage studies of plozasiran in patients with severe hypertriglyceridemia, showing a profile that analysts say could rival Ionis Pharmaceuticals’ recently approved Tryngolza. Arrowhead’s stock rose more than 20% to $91.48 at market open Wednesday following the announcement, while Ionis shares experienced a slight dip.
The global Phase 3 SHASTA-3 and SHASTA-4 trials enrolled around 750 patients with severe hypertriglyceridemia, a condition associated with an increased risk of acute pancreatitis. Both studies met their primary endpoint of triglyceride reduction versus placebo and achieved all prespecified secondary endpoints, including lower rates of acute pancreatitis compared to placebo. Treatment with plozasiran led to triglyceride reductions of 79% and 81% from baseline in the respective trials. Arrowhead also reported an "unprecedented 100% event reduction" in acute pancreatitis events versus placebo among high-risk patients, and a 78% reduction in the overall trial population.
Plozasiran, which was approved as Redemplo for familial chylomicronemia syndrome last November, demonstrated what Arrowhead described as a consistent safety and tolerability profile without new safety signals emerging during the trials. The company intends to present detailed results at the European Society of Cardiology Congress on August 30 and file a supplemental New Drug Application with the Food and Drug Administration before year-end, followed by submissions to other global regulators.
Stifel analysts commented on the data: “Overall on face this looks quite good and suggests ARWR’s plozasiran may be best-in-class.” H.C. Wainwright said, “We believe the readouts de-risk plozasiran’s move into the much larger sHTG population and support Arrowhead’s planned U.S. supplemental new drug application (sNDA) before year-end 2026.” The group assigned plozasiran a 90% probability of success in severe hypertriglyceridemia.
Stifel analysts also compared these results to those for Ionis’ RNA-targeted Tryngolza, which received FDA approval last month for severe hypertriglyceridemia after being approved as the first treatment for familial chylomicronemia syndrome in December 2024. They said, “As it relates to the AP [acute pancreatitis] event reduction data, there are multiple ways ARWR cuts it—and cross trial comparisons here come with caveats—but in general it looks like the efficacy of plozasiran/[Tryngolza] are very similar.”
Arrowhead CEO Christopher Anzalone said, “These compelling Phase 3 data in a broad sHTG study population that closely resembles today’s diverse patient landscape demonstrate plozasiran’s potential to dramatically change the way people are treated.”
