Ionis, Arrowhead hail data with triglyceride drugs at ACC

Drugs from Ionis and Arrowhead Pharma that block apolipoprotein C-III (apoC-III) have shown their value in treating diseases associated with elevated triglyceride levels in two studies presented at the American College of Cardiology annual congress.

The two companies are racing to bring their apoC-III inhibitors to market for severe hypertriglyceridaemia (HTG) and ultra-rare disorder familial chylomicronaemia syndrome (FCS).

At ACC, Ionis reported results from the phase 3 BALANCE trial of its olezarsen candidate in patients with FCS, showing that an 80 mg dose given by monthly subcutaneous injection reduced triglycerides by 44% after six months and 59% at 12 months. The reduction with a lower 50 mg dose was not statistically significant.

There was also a big reduction with Ionis’ drug in acute pancreatitis – an unpredictable and potentially fatal complication of FCS – with 11 cases in the placebo group versus one apiece in the two olezarsen arms.

FCS has no approved treatments in the US, although, an apoC-III-targeting drug from Ionis’ Akcea unit – Waylivra (volanesorsen) – has been approved for the disease in Europe. The FDA turned down the marketing application for Waylivra in 2018 after its advisors voted against approval.

Ionis said it plans to file for approval on the strength of the new data, which has also been published in the New England Journal of Medicine (NEJM). The company has previously suggested that olezarsen could become a $1 billion-plus product if approved for both FCS and severe HTG, which is a much larger indication.

Also presented at ACC was data from the phase 2b BRIDGE-TIMI 73a trial, in which olezarsen was shown to reduce triglycerides by 49% after six months in patients with HTG and high cardiovascular risk when added to standard therapy, and also cut other risk factors including apoC3 and apoB. The drug is currently in the phase 3 CORE trial programme in severe HTG, with results due towards the end of this year.

Arrowhead’s plozasiran, meanwhile, showed its worth in the phase 2b SHASTA-2 study in severe HTG patients at risk of acute pancreatitis, with an average 74% reduction in triglyceride levels at 24 weeks after just two doses of the drug, given at baseline and after 12 weeks.

According to the study, which was published in the journal JAMA Cardiology, at 48 weeks the reduction was 58%.

Among patients treated with plozasiran, 90.6% achieved a triglyceride level less than 500 mg/dL, the level associated with an increased risk of acute pancreatitis, at week 24, according to the company.

Plozasiran will soon start a pair of phase 3 trials in patients with severe HTG, and is also in the phase 3 PALISADE study in FCS with results due later this year.