The late-stage results come in advance of pivotal data that Ionis expects to provide for its antisense oligonucleotide Tryngolza in the third quarter, building up toward a regulatory submission in hypertriglyceridemia by year-end.
Ionis’ RNA-targeting antisense oligonucleotide therapy Tryngolza can significantly lower triglyceride levels in patients with moderate hypertriglyceridemia, according to a Monday readout from the company’s Phase III Essence study. Ionis is aiming for a Tryngolza label expansion into severe hypertriglyceridemia (sHTG), a condition that can lead to atherosclerosis and other heart diseases, after receiving an FDA nod in December 2024 as the first approved therapy for familial chylomicronemia syndrome (FCS).
Monday’s findings come as Ionis builds toward pivotal data expected in the third quarter. In a note to investors on Monday afternoon, analysts at William Blair said that Essence “serves predominantly as a supportive safety study” for Ionis’ Phase III CORE program, which positions Tryngolza for an sHTG approval.
“These data from ESSENCE are supportive of positive safety signals for olezarsen in sHTG,” the analysts wrote, noting that the study findings “are also auspicious for efficacy on the CORE studies’ primary endpoint” of reduction in triglyceride levels at six months after Tryngolza treatment.
In turn, findings from the CORE trials would allow the company to file for approval in “by year-end,” Sam Tsimikas, senior vice president of global cardiovascular development, said in a statement.
On Monday, Ionis revealed that the 50 mg dose of Tryngolza reduced triglyceride levels by 58% versus placebo at six months. This effect improved when using the 80 mg dose, which cut triglyceride concentrations by 61%, with both treatments hitting statistical significance.
Tryngolza likewise aced all of its key secondary endpoints, with the “vast majority” of treated patients achieving triglyceride levels below 150 mg/dL, indicating the normalization of triglycerides, as per Ionis’ announcement. The company did not provide a detailed safety breakdown on Monday, only noting that Tryngolza had a “favorable” tolerability profile with side effects being largely mild in severity.
Tryngolza is an antisense oligonucleotide that binds to the mRNA for apolipoprotein C-III, in turn tagging it for degradation. This mechanism of action facilitates the clearance of triglycerides from the bloodstream and helped Tryngolza secure its FCS approval late last year.
FCS is a rare and genetic disease that affects just around 3,000 patients in the U.S.—a limited market. Through Essence and the CORE program, Ionis is seeking to establish the potential of Tryngolza “to benefit the much broader population of people living with sHTG,” Tsimikas said on Monday.
Elsewhere in its oligonucleotide pipeline, Ionis in March out-licensed its investigational polycythemia vera therapy sapablursen to Japan’s Ono Pharmaceutical. The deal gave Ionis $280 million upfront and the potential to receive up to $660 million in milestones, plus royalties should sapablursen reach the market.
