Arrowhead Pharmaceuticals’ RNAi treatment has succeeded in a registrational test in patients with an ultra-rare lipid metabolism disorder, bolstering plans for a regulatory filing that follows hot on the heels of Ionis Pharmaceuticals.
The potential market entry of Arrowhead’s therapy, dubbed plozasiran, would mark the company’s first commercial product as well as one of the first treatment options for familial chylomicronemia syndrome (FCS). There are currently no FDA-approved drugs for the rare disease, although Ionis is already working towards approval for its contender, olezarsen.
The placebo-controlled Phase 3 PALISADE trial tested plozasiran, which targets apolipoprotein C-III, in 75 adults with FCS. The treatment met the primary endpoint, with the 25 mg dose achieving a median 80% reduction in fasting triglycerides at ten months versus a 17% reduction for placebo (p<0.001). FCS patients have extremely high triglyceride levels of 880 mg/dL or more, and these levels formed part of the trial’s inclusion criteria.
Arrowhead’s share price $ARWR increased almost 11% Monday morning to $25.43.
Plozasiran also met all key secondary endpoints, notably a “statistically significant” reduction in the incidence of acute pancreatitis versus placebo, according to a Monday release. Acute pancreatitis is a potentially fatal complication of FCS.
In September, Ionis unveiled Phase 3 results from 66 patients showing 80 mg olezarsen delivered a 44% placebo-adjusted reduction in triglyceride levels at six months (p<0.001). The treatment candidate also reduced acute pancreatitis events by 100%.
Despite the competition, Arrowhead CEO Christopher Anzalone said, “We see plozasiran data as best in class and with the potential to address multiple cardiometabolic diseases with substantial unmet need.”
Plozasiran demonstrated a “favorable safety profile” in the Phase 3 trial, with fewer severe and serious adverse events seen in the treatment arm compared with placebo.
The biotech plans to discuss the results with the FDA. It also expects to submit an NDA filing for plozasiran in FCS around the end of the year, enabling a possible 2025 launch, according to Chardan Research analysts. FCS affects one in every one to two million people globally and is currently managed by following an extremely restricted low-fat diet.
Last week, Arrowhead unveiled data showing plozasiran reduced levels of triglycerides, apolipoprotein B and non-HDL-C in a Phase 2b test in mixed hyperlipidemia.