For the better part of a year, the race to treat severe hypertriglyceridemia has run in a settled order: Ionis in front, Arrowhead a step behind, both selling RNA drugs into a market they are still building out from a rare disease toward millions of patients.
Late last month, Arrowhead posted a readout that gives Ionis something real to answer, and the figure doing the work is one the trial was never built to find. It sits with acute pancreatitis, the complication that puts sHTG patients in the hospital, and by Arrowhead's own account, the result caught the company off guard.
Here is what moved, and why the full data at month's end matters more than the topline number does today.
The Counterpunch
Ionis reached this market first. Its antisense drug Tryngolza (olezarsen) won FDA approval in December 2024 in familial chylomicronemia syndrome, the most severe form of severe hypertriglyceridemia. In June, it secured the bigger prize: clearance to treat any adult with sHTG, a condition that affects three to four million people in the US and carries a high risk of acute pancreatitis. That expansion rested on the twin CORE and CORE2 Phase III studies.
Arrowhead's answer arrived on July 22. Its RNA interference drug Redemplo (plozasiran), which reached the market last November with a label close to Tryngolza's, posted topline results from its own pair of Phase III trials, SHASTA-3 and SHASTA-4. Median triglyceride reductions were 79% and 81% from baseline. Across the broad study population, patients with triglycerides above 500 mg/dL with or without a prior pancreatitis episode, acute pancreatitis events fell by 78% versus placebo. In the high-risk group, they fell to zero.