Ionis Pharmaceuticals Advances RNA-Targeting Therapy for Triglyceride Reduction

Ionis Pharmaceuticals has made significant strides in developing its RNA-targeting antisense oligonucleotide therapy, Tryngolza, for the treatment of hypertriglyceridemia. The company recently announced positive results from its Phase III Essence study, demonstrating the drug's efficacy in lowering triglyceride levels in patients with moderate hypertriglyceridemia.

Essence Study Results

The late-stage Essence study revealed that Tryngolza significantly reduced triglyceride levels compared to placebo at six months. The 50 mg dose of Tryngolza decreased triglyceride levels by 58%, while the 80 mg dose showed an even more pronounced effect, reducing levels by 61%. Both dosages achieved statistical significance.

Tryngolza also met all key secondary endpoints, with the majority of treated patients achieving triglyceride levels below 150 mg/dL, indicating normalization of triglycerides. The company reported a favorable tolerability profile, with side effects being largely mild in severity.

Expanding Indications and Regulatory Strategy

Ionis is building on Tryngolza's success in familial chylomicronemia syndrome (FCS), for which it received FDA approval in December 2024. The company is now aiming to expand Tryngolza's label to include severe hypertriglyceridemia (sHTG), a condition associated with increased risk of atherosclerosis and other heart diseases.

The Essence study serves as a supportive safety study for Ionis' ongoing Phase III CORE program, which is designed to position Tryngolza for sHTG approval. Sam Tsimikas, senior vice president of global cardiovascular development at Ionis, stated that the company plans to file for approval in sHTG by year-end, pending positive results from the CORE trials expected in the third quarter.

Mechanism of Action and Market Potential

Tryngolza's effectiveness stems from its unique mechanism of action as an antisense oligonucleotide. It binds to the mRNA for apolipoprotein C-III, targeting it for degradation and facilitating the clearance of triglycerides from the bloodstream.

While FCS affects approximately 3,000 patients in the U.S., the potential expansion into sHTG treatment represents a significantly larger market opportunity. Ionis aims to establish Tryngolza's potential "to benefit the much broader population of people living with sHTG," according to Tsimikas.