Despite securing the industry’s first approval for familial chylomicronemia syndrome, BMO Capital Markets believes that Tryngolza’s regulatory triumph will not be a significant positive for Ionis. Instead, the firm is focusing on olezarsen’s readout in severe hypertriglyceridemia, a much larger market.
The FDA on Thursday cleared the U.S.’s first treatment for the rare disease familial chylomicronemia syndrome: Ionis Pharmaceuticals’ RNA-targeting therapy olezarsen, which will be marketed under the brand name Tryngolza.
Ionis expects to make Tryngolza available in the U.S. before the year ends, according to its announcement.
Affecting up to around 3,000 people in the U.S., familial chylomicronemia syndrome (FCS) is a rare, genetic form of severe hypertriglyceridemia (sHTG), or excessively high triglyceride levels. Patients with FCS are unable to effectively break down fats and remove triglycerides from the blood, resulting in several chronic health problems and complications such as fatigue, abdominal pain and acute pancreatitis. The last can prove fatal.
Tryngolza, an antisense oligonucleotide, addresses the triglyceride surplus in FCS patients by targeting and binding to the apolipoprotein C-III mRNA, thereby tagging it for destruction. As a result, Tryngolza lowers levels of apoC-III, a protein that under normal circumstances suppresses the action of the lipoprotein lipase enzyme. Through this mechanism of action, Tryngolza boosts the clearance of triglycerides from the blood.
With the FDA’s approval, Tryngolza can now be used in adult FCS patients as an adjunctive intervention to dietary adjustments, according to its label. The drug is designed to be delivered via subcutaneous injection.
Ionis backed Tryngolza’s application with data from the Phase III Balance study, which showed that an 80-mg dose of the treatment lowered triglyceride levels by a mean of 42.5%, adjusted for placebo. Over 12 months of follow-up, Tryngolza also led to a “clinically meaningful reduction” in acute pancreatitis events, according to Ionis’ announcement on Thursday.
In a statement, CEO Brett Monia called Tryngolza’s approval “a transformational moment” for FCS patients and their families. “For the first time, adults with FCS can now access a treatment that substantially reduces triglycerides and the risk of debilitating and potentially life-threatening acute pancreatitis.”
In a Friday note to investors, William Blair analysts highlighted the “relatively clean front page” for Tryngolza’s label, which has no “adverse event warnings besides potential hypersensitivity reactions.” Additionally, Ionis’ RNA-targeting therapy “received a broad label, permitting treatment of patients through both genetic and/or clinical diagnosis,” according to the analysts.
BMO Capital Markets, meanwhile, is more measured in its optimism. In a Thursday investor note, BMO analysts wrote that “we don’t expect FCS to be a significant opportunity” for Ionis, given the small market in the U.S. and impending competition from Arrowhead’s plozasiran. The firm projects $341 million in peak sales for Tyngolza in this indication.
Instead, the BMO analysts focused on sHTG, which is a much broader indication and “can confer a meaningfully larger opportunity” for olezarsen. A Phase III readout in sHTG is expected in the second half of 2025, according to the analysts, adding that BMO anticipates “stronger [triglyceride] lowering vs. FCS.” BMO expects olezarsen’s peak sales in sHTG to be five or six times higher than in FCS.
