Plozasiran

Arrowhead Pharmaceuticals on Monday shared new open-label data in about a dozen patients for a program designed to improve certain kidney disease outcomes by targeting complement pathways. The program, known as ARO-C3, is an RNAi therapy that aims to reduce levels of complement component 3 in the liver. Arrowhead is testing ARO-C3 in IgA nephropathy. Novartis, Vertex, Biogen and Otsuka are also developing drugs using varying mechanisms of action that aim to treat the rare chronic kidney disease. Novartis’ drug Fabhalta received accelerated approval in IgA nephropathy last August. In Arrowhead’s trial, researchers enrolled 14 patients who received three doses of ARO-C3 over 16 weeks and were followed through 24 weeks. At that time, patients saw an average 41% reduction in a measurement of kidney stabilization called the urine protein-to-creatinine ratio, or UPCR. UPCR plays an important role in IgA nephropathy development, since Fabhalta was approved based on its improvements in the measurement. In Fabhalta’s Phase 3 study with 125 patients, the drug reduced UPCR by 44% relative to baseline after nine months, compared to 9% of patients on placebo. ARO-C3 is considered a “non-core” program for Arrowhead, according to B Riley Securities analyst Mayank Mamtani, who believes the most value that ARO-C3 will bring is by being partnered out in order to provide cash for the potential launch of plozasiran, an Arrowhead drug being developed for metabolism disorders. Two Phase 3 studies for plozasiran in severe hypertriglyceridemia are currently recruiting patients. Leerink analyst Mani Foroohar also described ARO-C3 as having a “low” impact on Arrowhead’s stock price $ARWR , which was down about 4% on Monday morning. Arrowhead executives said during their last earnings call that they are open to finding a partner for ARO-C3.

Plozasiran led to an 80% median reduction in baseline of fasting triglyceride level in a Phase III trial. Image credit: Shutterstock/ peterschreiber.media. The US Food and Drug Administration (FDA) has accepted a new drug application (NDA) for Arrowhead Pharmaceutical’s plozasiran in the same indication, a month after the first treatment was approved by the regulator for the treatment of familial chylomicronemia syndrome (FCS). The Prescription Drug User Fee Act (PDUFA) action date for Arrowhead’s candidate is 18 November 2025, with the FDA adding that it currently does not intend to hold an advisory committee meeting. FCS is a rare metabolic disease that prevents the body from breaking down fats due to a mutation in lipoprotein lipase. The resulting elevated levels of triglycerides can lead to chronic abdominal pain, diabetes, hepatic steatosis, and acute and potentially fatal pancreatitis. Arrowhead’s NDA is supported by data from the Phase III PALISADE (NCT04998201) trial, along with supportive confirmatory evidence from Phase II studies in the SUMMIT programme. Plozasiran lowered triglyceride levels and reduced acute pancreatitis risk, leading the trial to meet primary and all multiplicity-controlled key secondary endpoints. Plozasiran is an RNA interference (RNAi) therapeutic that cuts the production of apolipoprotein C-III (APOC3), a key regulator of triglyceride metabolism. Last month, Ionis Pharmaceuticals’ Tryngolza (olezarsen) became the first treatment approved for FCS by the FDA. Similar to plozasiran, Tryngolza is also an RNA-based drug designed to reduce the body’s production of APOC3. Direct comparisons between the two drugs have not been made in clinical trials. High-dose Tryngolza led to a 44% placebo-adjusted drop in triglyceride levels from baseline at six months, with this rising to 59% in months six to 12. For 25mg plozasiran, the median reduction in baseline fasting triglyceride level was 80%. Tryngolza is forecast to generate $303m in annual revenue by 2030, according to GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology . Arrowhead’s CEO Chris Anzalone said: “We are laser-focused on our ongoing work to ensure an efficient and successful commercial launch this year, pending FDA review and approval.” In addition to targeting FDA approval, Arrowhead stated that it intends to submit applications for plozasiran in FCS treatment to additional regulatory authorities this year. The pharma company also has further lipid-based plans for plozasiran and is investigating the drug in severe hypertriglyceridemia and mixed hyperlipidemia. Moreover, Arrowhead placed a target on the obesity treatment space by advancing two RNAi-based candidates to clinic in August 2024.