Arrowhead fortifies position in tight Ionis race, with RNAi med lowering triglycerides in phase 3

Arrowhead Pharmaceuticals’ RNA interference (RNAi) therapeutic lowered triglycerides in patients with a rare metabolic disease that prevents the body from breaking down fats during a phase 3 trial.

Plozasiran met the main goal of the late-stage PALISADE test for patients with familial chylomicronemia syndrome (FCS) by lowering triglycerides, according to a Monday press release. The therapy also met key secondary endpoints of reducing the incidence of acute pancreatitis compared to placebo.

The results build on earlier data from the midstage SHASTA-2 and MUIR studies for patients with severe hypertriglyceridemia (SHTG) and mixed hyperlipidemia.

Arrowhead was examining the placebo-adjusted median change in triglycerides at Month 10. Patients who received 25- and 50-mg doses of plozasiran has 80% and 78% reductions, respectively, with a maximum reduction of 98% noted. At Month 12, patients had 78% and 73% reductions, respectively, with a maximum reduction of 99% recorded.  Meanwhile, patients on placebo had just a 17% reduction at Month 10 and 7% at Month 12.

The key secondary endpoints, which were met, included a change in baseline of fasting triglycerides and change in fasting APOC3.

Treatment-emergent adverse events were even across the plozasiran and placebo groups, and severe events were less common in patients who received the study drug. The most common events were abdominal pain, COVID-19 and headache.

CEO Christopher Anzalone, Ph.D., said Arrowhead will now take the results to the FDA to discuss a new drug application filing in FCS. At the same time, the company will continue work on other metabolic disorders for plozasiran including phase 3 tests in SHTG and mixed hyperlipidemia.

In April, Arrowhead showcased results in SHTG linking the RNAi medicine to improved outcomes through Week 48.

Plozasiran, previously known as ARO-APOC3, is designed to lower production of apolipoprotein C-III (APOC3), a part of triglyceride-rich lipoproteins and a regulator of triglyceride metabolism. Treatment with the drug aims to reduce APOC3 levels, therefore reducing triglycerides and restoring lipids to normal levels.

Arrowhead is in a tight race with Ionis Pharmaceuticals, which is also working on late-stage tests for antisense candidate olezarsen in the same family of disorders. Data presented in April showed olezarsen’s efficacy slide slightly from a 100% reduction in acute pancreatitis events that had been previously touted.

Nevertheless, Ionis is well ahead, with a regulatory filing in FCS planned for later this year.

The results sent Arrowhead’s shares up 7% as the markets opened Monday to $24.64 compared to $22.95 at the previous close.

Analysts predict that plozasiran could reach sales of $707 million by 2032. This is due to the therapy’s ability to reduce triglycerides and address many forms of dyslipidemia, a family of diseases in which lipids or lipoproteins are found in abnormally high or low amounts in the blood, the presence of which is a known risk factor for heart disease.