Ionis is planning a supplemental submission by the end of the year to expand Tryngolza into severe hypertriglyceridemia. If granted, William Blair expects the antisense drug to be “transformational” for this indication.
Ionis Pharmaceuticals’ antisense oligonucleotide Tryngolza significantly reduced triglyceride levels as well as acute pancreatitis events in back-to-back late-stage studies of severe hypertriglyceridemia, helping the California biotech build the case for a label expansion into this indication.
Writing to investors early on Monday, William Blair analysts called Ionis’ readout “game-changing,” noting that if it does win the FDA’s approval, Tryngolza “will likely be transformational for the treatment for sHTG [severe hypertriglyceridemia] across a potential broad spectrum of patients.” Tryngolza is currently only indicated for patients with familial chylomicronemia syndrome (FCS), a rare genetic disease that causes high blood triglyceride levels.
In its presentation on Saturday at the 2025 Scientific Sessions of the American Heart Association, Ionis showed that at 6 months, Tryngolza led to a 72% mean reduction in fasting triglyceride levels—an effect that was sustained through 12 months of follow-up. Ionis’ antisense oligonucleotide also lowered acute pancreatitis events by 85%.
Moreover, 89% of patients on 50-mg Tryngolza saw their triglyceride levels drop to below 880 mg/dL, the threshold typically associated with the highest risk of acute pancreatitis. The same dose of the drug brought 34% of patients below 150 mg/dL, the bar for normal triglyceride levels.
In a Monday note, William Blair called these data “groundbreaking, with clear demonstrations of reduced pancreatitis risk” in the study’s overall patient population and across key subgroups, such as those who were at highest risk of this complication. Tryngolza, the analysts added, also showed “near-immediate protection from AP [acute pancreatitis] events.”
Ionis’ late-stage success continues what has been a winning streak for the biotech in recent months. In August, for instance, Ionis won the FDA’s approval for Dawnzera, the industry’s first RNA-targeting therapy meant as a prophylactic option for hereditary angioedema (HAE). Dawnzera is indicated for patients 12 years and older.
A month later, the company scored a pivotal win for its antisense therapy zilganersen in Alexander disease, a rare and often fatal condition that manifests as progressive neurological disability and loss of muscle function. Results from a Phase I–III study showed a 33% improvement in the 10-meter walk test, a measure of gait stability, in patients treated with zilganersen. Ionis is planning an FDA submission for the drug in the first quarter of 2026.
“Ionis is starting to become a fully diversified commercial business with the wholly owned launches of Tryngolza in FCS,” William Blair wrote on Monday, “and Dawnzera in HAE prophylaxis.” Tryngolza’s potential expansion into sHTG—which the group said was “de-risked”—will also play into this overall business profile.
