FDA Fast-Tracks Arrowhead's Breakthrough Drug for Dangerous Triglyceride Levels

Arrowhead Pharmaceuticals has secured a key milestone for its experimental drug, plozasiran. The US Food and Drug Administration (FDA) granted it Breakthrough Therapy designation for treating severe hypertriglyceridemia—a condition linked to a higher risk of acute pancreatitis. The move follows ongoing global trials and the approval of a related treatment, REDEMPLO, in multiple countries since late 2024.

Plozasiran is designed as a first-in-class RNA interference (RNAi) therapy. It targets apolipoprotein C-III (apoC-III), a protein that regulates triglyceride levels in the blood. The drug aims to lower triglycerides in adults with severe hypertriglyceridemia (levels ≥500 mg/dL) when used alongside dietary measures.

Three major Phase 3 studies are currently underway. The SHASTA-3 and SHASTA-4 trials focus on patients with severe hypertriglyceridemia, while MUIR-3 examines those with moderate levels (150–500 mg/dL). All three studies are expected to conclude by mid-2026.

Arrowhead plans to submit a supplemental New Drug Application (sNDA) to the FDA by the end of that year. The company's earlier drug, REDEMPLO (olezarsen), received approval in the US in December 2024 and later in the EU, UK, Canada, Australia, and Japan. By early 2026, over 2,000 patients worldwide had been treated with REDEMPLO, though common side effects included hyperglycemia, headaches, nausea, and injection site reactions.

Severe hypertriglyceridemia remains a challenging condition with few treatment options. Current therapies often fail to adequately reduce the risk of pancreatitis, leaving many patients in need of more effective solutions.

The FDA's Breakthrough Therapy designation accelerates plozasiran's development timeline. If approved, it could offer a new option for patients with dangerously high triglyceride levels. The drug's progress will depend on the outcomes of the ongoing Phase 3 trials, with results due in mid-2026.