Arrowhead Pharmaceuticals Receives Breakthrough Therapy Designation for Plozasiran in Severe Hypertriglyceridaemia
Wednesday, December 03, 2025
Arrowhead Pharmaceuticals has received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for its investigational therapy plozasiran.
SHTG is marked by triglyceride levels above 500 mg/dL. The most extreme form, familial chylomicronaemia syndrome (FCS), typically involves TG levels exceeding 880 mg/dL. Individuals with SHTG face a heightened risk of acute pancreatitis, which may involve repeated episodes and hospital admissions. The risk of pancreatitis rises as levels of triglyceride-rich lipoproteins, especially chylomicrons, increase. Few therapies are currently available that can reliably lower TG levels below recommended thresholds.
Plozasiran is a first-in-class RNA interference (RNAi) therapy designed to reduce production of apolipoprotein C-III (apoC-III), a protein that plays a central role in triglyceride regulation. High levels of apoC-III slow the breakdown and clearance of triglyceride-rich lipoproteins, leading to elevated TG levels. By lowering apoC-III, plozasiran aims to reduce triglycerides and restore lipid levels to healthier ranges.
The therapy is being evaluated in multiple Phase 3 trials, including SHASTA-3, SHASTA-4, SHASTA-5 for severe hypertriglyceridaemia and the MUIR study for mixed hyperlipidaemia. In the US, plozasiran is approved as REDEMPLO for reducing triglycerides in adults with familial chylomicronaemia syndrome, with additional global submissions under way.
REDEMPLO is an siRNA-based treatment approved in the US to lower triglycerides in adults with familial chylomicronaemia syndrome. It works by reducing apoC-III production in the liver, leading to sustained decreases in triglyceride levels. It is currently the only approved therapy studied in both genetically confirmed and clinically diagnosed patients with FCS.
The designation covers the use of plozasiran, alongside dietary measures, to lower triglyceride (TG) levels in adults with severe hypertriglyceridaemia (SHTG), defined as TG levels of 500 mg/dL or higher. SHTG affects millions of people worldwide, and current treatment options remain limited.
Breakthrough Therapy designation is intended to speed up the development and review of medicines that target serious conditions and show early signs of offering meaningful improvement over existing therapies.
Arrowhead expects to complete its SHASTA-3, SHASTA-4, and MUIR-3 Phase 3 studies by mid-2026, with plans to submit a supplemental New Drug Application in the US by the end of 2026.
The company also aims to pursue approvals from global regulatory authorities.
Source: arrowheadpharma.com
