Ionis Pharmaceuticals has hit a “home run,” according to analysts at Citi, with data in two phase 3 trials that show the ability of Tryngolza (olezarsen) to reduce triglycerides and acute pancreatitis (AP) events in individuals with severe hypertriglyceridemia (sHTG).
In the largest sHTG study ever run, the trials achieved their primary endpoint with placebo-adjusted reductions of 55% and 72% in triglycerides after six months of treatment. Pooled data from the trials also showed as a secondary prespecified endpoint that Tryngolza reduced the risk of AP events by 85% after patients were on Tryngolza for a year.
“Taken together, we view these data as the best-case scenario for Ionis and substantially exceeding our expectations,” Myles Minter, Ph.D., of William Blair wrote.
Meanwhile, analysts from Jefferies jacked up their peak sales potential of Tryngolza from $1.5 billion to $2.5 billion.
Ionis said that it will present full results at a future medical meeting and plans to submit for FDA approval of Tryngolza in sHTG by the end of this year and to regulators outside of the U.S. in 2026.
With the results, Ionis’ share price zoomed by 33% by publication time on Tuesday morning.
“We believe that this is an unprecedented and historical achievement in the field of lipidology, where the quest to reduce the risk of acute pancreatitis in sHTG has been ongoing for nearly 50 years,” Sam Tsimikas, M.D., Ionis’ chief of global cardiovascular development, said during a Tuesday webcast.
The CORE and CORE2 studies included 1,063 sHTG patients who were required to be on standard-of-care lipid-lowering therapy throughout. In both trials, Tryngolza was tested at 80mg and 50mg doses, each injected monthly. In CORE, which included 617 patients, the placebo-adjusted triglyceride reductions were 72% and 63% at the respective doses. In CORE2, which included 446 participants, the placebo-adjusted triglyceride figures came in at 55% and 49% at the respective doses.
Helping explain the differences in the trials was that at baseline, 47% and 37% of participants had fasting triglycerides of at least 880 mg/dL in CORE and CORE2, respectively. Levels below 150 mg/dL are typically considered healthy for adults. In CORE, the placebo group had a 0.5% reduction in triglycerides, compared to a 14% reduction in triglycerides in the placebo group in CORE2.
“Olezarsen had a very large treatment effect, reducing the risk of pancreatitis by 85% in only one year of treatment, definitely proves the link between elevated triglycerides and acute pancreatitis in sHGT,” Tsimikas added.
Self-injected Tryngolza is an RNA-targeted ligand conjugated antisense (LICA) medicine designed to lower the body's production of apolipoprotein C-III (apoC-III) in the liver.
The FDA approved the drug in December of last year as the first drug to treat familial chylomicronemia syndrome (FCS), a disorder that prevents the body from breaking down fats, leading to elevated triglyceride levels in the blood. The underdiagnosed condition affects an estimated 3,000 people in the U.S.
By contrast, a much larger patient population awaits in sHTG, which affects approximately 3 million in the U.S., including roughly 1.2 million who are considered high-risk. Those in the high-risk group have triglyceride counts of greater than 880 mg/dL or greater than 500 mg/dL for those who have a history of AP.
“At launch, we plan to prioritize high-risk sHTG treaters in the U.S. made up of cardiologists, endocrinologists and lipidologists. These specialists manage the vast majority of the high-risk sHTG patient population,” Kyle Jenne, Ionis’ commercialization chief, said on Tuesday.
“We expect the drug will be very well-received by physicians and payors alike, as both have strong interest in avoiding expensive and potentially deadly pancreatitis hospitalizations for sHTG patients,” Citi analysts David Lebowitz and Ike Lee wrote. “Additionally, we believe premium pricing could be justified for Tryngolza as the sole therapy to have shown such benefits on reducing pancreatitis.”
The sHTG results come less than two weeks after Ionis secured an FDA approval for Dawnzera to treat a rare genetic condition, hereditary angioedema (HAE).