With Phase 3 data showing what analysts called a “potentially best-in-class profile,” Arrowhead Pharmaceuticals plans to submit for FDA approval of plozasiran by the end of the year—hoping to follow to market Ionis Pharmaceuticals’ Tryngolza, which got the regulator’s nod in severe hypertriglyceridemia last month.
Arrowhead Pharmaceuticals reported topline data Wednesday from two late-stage studies of plozasiran in patients with severe hypertriglyceridemia showing a “potentially best-in-class profile” that could give Ionis Pharmaceuticals’ recently approved Tryngolza a run for its money, according to analysts.
Arrowhead’s stock spiked more than 20% to $91.48 at market open Wednesday on the news, while Ionis shares dipped slightly.
The results are from the global Phase 3 SHASTA-3 and SHASTA-4 trials, which studied the siRNA treatment in around 750 patients with severe hypertriglyceridemia (sHTG), a condition that significantly increases the risk of acute pancreatitis, according to Arrowhead’s press release.
Both studies met the primary endpoint of triglyceride reduction versus placebo, as well as all prespecified secondary endpoints, including lower rates of acute pancreatitis compared to placebo, the biotech said. Specifically, treatment with Arrowhead’s drug led to triglyceride reductions of 79% and 81% from baseline in SHASTA-3 and SHASTA-4, respectively. The company also claimed an “unprecedented 100% event reduction” in acute pancreatitis events versus placebo for high-risk patients. This metric was 78% in the overall trial population.
Plozasiran, approved in November as Redemplo for familial chylomicronemia syndrome (FCS), showed a “consistent” safety and tolerability profile in the trials, with no new safety signals, Arrowhead said. The company plans to present detailed results from the trial at the European Society of Cardiology Congress on Aug. 30 and file a supplemental New Drug Application (sNDA) with the FDA before the end of the year, followed by applications to other global regulators.
“Overall on face this looks quite good and suggests ARWR’s plozasiran may be best-in-class,” Stifel analysts wrote of the data in a note to investors.
H.C. Wainwright were similarly bullish on the asset. “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 90% probability of success in sHTG.
Stifel compared the data to Ionis’ RNA-targeted Tryngolza, which won FDA approval last month for sHTG. This followed a December 2024 approval as the first-ever treatment for FCS.
“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,” the analysts wrote. “For Ionis, this increases the intensity of competition in the SHTG space—though good ARWR data were mostly expected.”
Arrowhead CEO Christopher Anzalone was more effusive on the readouts. “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,” he said in a prepared statement on Wednesday.
