Ionis preps filings for olezarsen in rare disease FCS

Center for RNA Therapeutics

Ionis Pharma is preparing to file for regulatory approval of its experimental therapy olezarsen for familial chylomicronaemia syndrome (FCS) in the US and Europe after the drug met its targets in a phase 3 trial.

The rare genetic disorder is a serious disease that prevents the body from breaking down triglyceride fats consumed in the diet, leading to very high levels that often do not respond to dietary restrictions or medications.

It can cause a wide range of symptoms, including acute pancreatitis that can be fatal, as well as complications affecting the eyes, skin and other tissues and organs.

In the 66-patient BALANCE study, olezarsen (formerly IONIS-APOCIII-LRx) met its primary objective of reducing triglyceride levels in the blood compared to placebo and also achieved an absolute reduction in acute pancreatitis, cutting cases to zero at the highest test dose of 80 mg given as a monthly injection after six months. A lower 50 mg dose did not work significantly better than placebo.

The antisense-based drug is designed to inhibit the body’s production of a protein called apoC-III that regulates triglycerides in the blood.

It has already been granted a fast-track designation by the FDA as a treatment for FCS, which has no approved treatments and usually fails to respond to triglyceride-lowering drugs like fibrates, niacin, omega-3 fatty acids, and high-dose statins. In BALANCE, patients were generally already taking these therapies to try to control symptoms.

FCS has an estimated population frequency of around one person per 700,000 to one million population, suggesting cases in the US would be in the hundreds, but is thought to be underdiagnosed.

Ionis said it plans to file for approval in the US first, likely early next year, with applications in Europe and elsewhere following thereafter.

The company’s Akcea unit already sells an RNA interference (RNAi) drug targeting apoC-III for FCS patients at high risk of acute pancreatitis – Waylivra (volanesorsen) – but only in Europe, as the FDA turned down the marketing application for the drug in 2018. Sales of Waylivra by European licensee Sobi were around $14 million last year.

Olezarsen is also being developed for severe hypertriglyceridaemia (SHTG), a much larger potential patient population, with the first phase 3 results from the CORE clinical trials programme due in 2024. Ionis said earlier this year that the drug has the potential to make more than $1 billion a year in sales at its peak.