With an FDA approval for Tryngolza (olezarsen) to treat the rare genetic disorder familial chylomicronemia syndrome (FCS), Ionis Pharmaceuticals enters a new era.

While Ionis has gained several FDA nods in its 35 years in existence, Tryngolza will be the first medicine the Carlsbad, California-based biotech will commercialize on its own. In the past, the company has always licensed the rights of its drugs to a development partner.

"Tryngolza's approval is a pivotal moment for Ionis," Ionis CEO Brett Monia, Ph.D., said during a post-approval conference call Thursday. "Ionis was founded on the principle of turning ground-breaking science and technology into life-changing medicines for devastating diseases."

Five years ago, when Monia took control, the company decided to change its strategic course “to fully maximize the value of our innovative medicine by retaining and delivering them directly to patients.” Tryngolza is the first of four independent launches Ionis plans to conduct through 2027.

Last year—nearly to the day—when Ionis scored a pre-holiday FDA approval for Wainua (eplontersen) to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN), it did so with its partner AstraZeneca to build its "infrastructure," Monia said.

As for Tryngolza, it becomes the first approved medicine in the U.S. to treat FCS, a condition which prevents the body from breaking down fats, leading to elevated triglyceride levels in the blood.

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.

A self-injected monthly therapy, Tryngolza has been shown to significantly reduce triglycerides, which can lead to the primary complication with FCS—potentially fatal episodes of acute inflammation of the pancreas.

The FDA approval was based on results from a phase 3 trial which showed that the drug triggered a 42% reduction in triglyceride levels after six months. Reductions in triglycerides from baseline to 12 months came in at 57%.

Tryngolza also reduced acute pancreatitis (AP) events over 12 months. In the Tryngolza group, one in 22 patients had a single AP episode. In the placebo group, seven of 23 patients experienced a combined 11 AP episodes.

It was the first time a trial showed that lowering triglycerides could also reduce the risk of pancreatitis, Monia said. 

“With no treatment options previously available, we were limited to relying only on extremely strict diet and lifestyle changes as the sole preventative treatment option,” Alan Brown, M.D., the trial investigator and clinical professor of medicine at the Rosalind Franklin University of Medicine and Science, said in a press release.

With the nod, Tryngolza can be used as an adjunctive treatment to diet restrictions. Ionis has won a broad label for Tryngolza, as it is indicated for adults with FCS regardless of whether their disease was genetically or clinically confirmed.

The company will charge $595,000 for an annual regimen of Tryngolza. Now the job will be to find the approximately 3,000 patients who have FCS in the U.S.

“The vast majority of this population remains unidentified and undiagnosed today,” Ionis’ chief commercial officer Kyle Jenne said during the conference call. “As is the case with many rare diseases with no treatment options, FCS has been a largely unrecognized disease with a lack of awareness precluding patients from achieving diagnosis.” 

The company is setting up Tryngolza to be endorsed in a much larger indication, severe hypertriglyceridemia (sHTG), which is also a disorder that results from too may triglycerides in the blood and affects an estimated 3 million in the U.S.

Ionis expects a phase 3 trial of the treatment in sHTG to read out in the second half of next year with a potential approval to follow in 2026. Like FCS, the disorder is associated with cardiovascular problems, along with an increased risk of pancreatitis.

With a possible second approval for Tryngolza, GlobalData is projecting sales to reach $849 million in 2032.

Ionis also is looking forward to an August 21, 2025, target date for the FDA decide on donidalorsen as a treatment for hereditary angioedema.