Ionis plans NDA for first wholly-owned drug after positive PhIII data in familial chylomicronemia syndrome

Ionis is another step closer to the launch of its first independent drug, touting positive Phase III data for olezarsen in patients with a rare genetic disorder called familial chylomicronemia syndrome (FCS).

Ionis said Tuesday it has plans to file for an NDA in early 2024 and for approvals in the EU after olezarsen hit its primary endpoint in the BALANCE study: a statistically significant reduction in triglyceride levels after six months on 80 mg of the drug compared to placebo, earning a p-value of 0.0009. A key secondary endpoint also showed promise, with olezarsen reducing acute pancreatitis events by 100%. In the placebo arm, there were 11 instances of pancreatitis.

FCS, which is characterized by high triglyceride levels because the body can’t break down fats consumed through diet, can lead to potentially fatal pancreatitis as well as severe abdominal pain, according to Ionis.

Sotirios Tsimikas

“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 SVP of cardiovascular development Sotirios Tsimikas said in a statement.

“In this study, people with FCS treated with olezarsen along with background therapy and a low-fat diet had a substantially reduced risk of recurrent attacks of acute pancreatitis,” he added.

Ionis has historically been one of the biggest names in antisense technology, inking licensing deals with Biogen, AstraZeneca, Roche and others, with several of the partnered programs either approved (most notably Spinraza) or in late-stage trials. But CEO Brett Monia has also been boasting of a growing in-house pipeline.

While Ionis will present more detailed data from the 66-patient study at a future medical meeting, the company included additional data points for olezarsen, like a 75% reduction in apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood.

As for safety and tolerability, there were more adverse events in the placebo group, largely because of pancreatitis, Ionis said. Most other adverse events were mild, like injection site reactions. One death was reported but wasn’t related to the drug, according to the company.

Ionis also investigated 50 mg of the drug in patients but did not reach statistical significance on the primary endpoint.

Ionis CEO Brett Monia said in a statement that olezarsen has the “potential” to become the standard of care for FCS patients.

“We look forward to submitting these data to the FDA and anticipate that olezarsen will be the first of many medicines from our wholly owned pipeline that we bring to people with debilitating diseases,” Monia added.

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