Arrowhead Announces Successful Phase 3 Results for Plozasiran in Familial Chylomicronemia Syndrome

Arrowhead Pharmaceuticals recently released promising results from their Phase 3 PALISADE study of plozasiran, an investigational RNA interference (RNAi) therapy aimed at treating familial chylomicronemia syndrome (FCS). This rare genetic disorder is characterized by extremely high triglyceride levels, which can lead to severe health issues such as acute pancreatitis, diabetes, and chronic abdominal pain. The PALISADE study met its primary endpoint of reducing triglycerides and achieved all key secondary endpoints, including a reduction in acute pancreatitis incidents compared to a placebo.

The study enrolled 75 patients from 39 sites across 18 countries, who were randomized to receive 25 mg or 50 mg of plozasiran or a placebo every three months. At the 10-month mark, patients on plozasiran showed a median reduction in triglycerides of up to 80%, with a maximal reduction of 98%. These results were significantly better than the placebo group, which saw a median reduction of only 17%. Additionally, plozasiran demonstrated mean reductions in Apolipoprotein C-III (APOC3) of up to 94% at month 10. This protein is known to inhibit the breakdown of triglyceride-rich lipoproteins, thereby increasing triglyceride levels in the blood.

The study also highlighted the safety profile of plozasiran, which showed a comparable number of treatment-emergent adverse events (AEs) between the plozasiran and placebo groups. Common AEs included abdominal pain, COVID-19, nasopharyngitis, headache, and nausea. Serious adverse events were less frequent in the plozasiran group compared to the placebo group.

Dr. Bruce Given, Arrowhead’s Chief Medical Scientist, emphasized that the Phase 3 PALISADE results build upon the positive outcomes seen in earlier Phase 2 studies, suggesting that plozasiran could become a promising therapy for various cardiometabolic disorders. The company plans to present these findings at upcoming medical conferences and engage with regulatory authorities to discuss filing a New Drug Application (NDA) for FCS.

Christopher Anzalone, Arrowhead’s President and CEO, expressed optimism about the potential of plozasiran to address multiple cardiometabolic diseases with significant unmet needs. He noted that the success of this investigational RNAi-based medicine is a testament to the hard work of Arrowhead’s team, collaborators, and the FCS community. The company is also advancing additional Phase 3 studies for other patient populations, further underscoring the broad potential of plozasiran.

Arrowhead plans to showcase recent data from its cardiometabolic pipeline, including the PALISADE study results, at a Cardiometabolic event on June 25, 2024, as part of its Summer Series of R&D Webinars. The company is also preparing to present the full data set from the Phase 3 PALISADE study at future medical conferences.

Plozasiran, initially referred to as ARO-APOC3, is designed to reduce the production of APOC3, thereby lowering triglyceride levels and normalizing lipid profiles. It has received Orphan Drug Designation and Fast Track Designation from the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation from the European Medicines Agency, which could expedite its path to market.

Arrowhead Pharmaceuticals remains dedicated to developing innovative RNAi-based therapies to tackle intractable diseases by silencing the genes responsible for them. The company is committed to leveraging RNA interference technology to create rapid, profound, and durable gene knockdowns, aiming to bring new treatments to patients as swiftly and efficiently as possible.