Pharma, BioPharma

Ionis Posts Trial Data in Rare Disease That Position It to Finally Set Out on Its Own

Ionis Pharmaceuticals’ olezarsen has Phase 3 results showing the therapy handily beat a placebo at reducing fat levels in the blood due to a rare, inherited metabolic disorder with no FDA-approved drugs. Ionis plans early 2024 submissions for what could become the first medicine it commercializes without a partner.


Ionis Pharmaceuticals has revenue from commercialized medicines, but those products reached the market in the hands of biopharma industry partners. The genetic medicines company does have wholly owned assets, and one of them now has preliminary Phase 3 data that put it on the path for an FDA submission.

The drug, olezarsen, is a potential treatment for familial chylomicronemia syndrome, or FCS. The rare, inherited disease leads to the inability to break down triglycerides, which are fats consumed from food. High triglyceride levels can lead to acute pancreatitis, severe inflammation of the pancreas that can become fatal. Patients also face an increased risk of developing cardiovascular disease. FCS has no FDA-approved therapies, but Carlsbad, California-based Ionis aims to bring patients the first one.

Ionis specializes in antisense oligonucleotide drugs, genetic medicines that bind to messenger RNA to inhibit production of a disease-causing protein. Olezarsen is designed to block the body’s production of apoC-III, a liver protein that regulates triglyceride metabolism in the blood.

The Ionis drug is being tested in a placebo-controlled Phase 3 study that enrolled 66 adults with a confirmed FCS diagnosis. In addition to the study drug, patients were allowed to continue taking other therapies they had been using to manage FCS including statins, fibrates, and omega-3 fatty acids. Study participants were randomly assigned to receive either a high or low dose of olezarsen or a placebo. The doses were administered as subcutaneous injections once every four weeks.

The clinical trial’s main goal is measuring at six months the change from baseline in fasting triglyceride levels. On Tuesday, Ionis reported the study met this goal, with statistically significant results from the high dose group showing a greater than 75% reduction in apoC-III levels compared to the placebo group. That’s better than the results from the dose-ranging Phase 2 study, which showed a 60% reduction in triglyceride levels at six months. The company said the lowering of protein levels in the Phase 3 test continued through 12 months.

The preliminary Phase 3 results also showed the study drug met a key secondary goal of reducing acute pancreatitis events. In the high dose group, the reduction was 100%—0 events compared to 11 in the placebo group. Olezarsen’s effect was dose dependent. While results from the lower of the two doses tested showed a reduction in pancreatitis, it did not achieve statistical significance on the main goal of lowering triglyceride levels.

“These positive olezarsen topline results represent an important advance for people with FCS who live in constant fear of unpredictable and potentially fatal attacks of acute pancreatitis,” Sam Tsimikas, Ionis’s senior vice president, global cardiovascular development, said in a prepared statement. “With no currently FDA-approved treatments, people with FCS live with debilitating abdominal pain and must maintain an extremely restrictive diet consisting of less than 20 grams of fat per day.”

Ionis’s commercialized products include Spinraza, a spinal muscular atrophy therapy developed in partnership with Biogen, and Tegsedi, a once-weekly treatment for hereditary transthyretin amyloidosis (hATTR) developed in partnership with Akcea Therapeutics (which Ionis acquired in 2020). Olezarsen’s monthly dosing would offer an advantage over once-a week Waylivra, an antisense therapy for FCS from Akcea that won approvals in Europe and other markets but was rejected by the FDA in 2018. Eplontersen, a once-monthly hATTR therapy developed in partnership with AstraZeneca, is expected to receive an FDA decision in December.

FCS affects an estimated 1 to 2 million patients worldwide, according to Ionis. In addition to the tests of olezarsen in FCS, the company is also developing the drug for severe hypertriglyceridemia, which is high triglyceride levels resulting from conditions such as obesity and type 2 diabetes. In an investor presentation, Ionis said FCS and severe hypertriglyceridemia together represent an opportunity to top $1 billion in peak sales.

Ionis said it plans to file regulatory submissions for olezarsen in early 2024 in the U.S. and Europe. The company also plans to present the Phase 3 data at a future medical meeting.

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