Plozasiran Phase 2 Results: Published in JAMA Cardiology and Presented at ACC.73

Arrowhead Pharmaceuticals has unveiled the final data from its Phase 2 SHASTA-2 study, which focused on the investigational drug plozasiran for severe hypertriglyceridemia (SHTG). The study demonstrated significant and sustained reductions in triglycerides and Apolipoprotein C-III (APOC3) levels, leading to improved atherogenic lipoprotein profiles. The results were revealed at the American College of Cardiology's 73rd Annual Scientific Session & Expo and published in JAMA Cardiology.

The study's principal investigator, Daniel Gaudet, highlighted the importance of these findings, given the limited treatment options for patients with SHTG. The trial showed that plozasiran led to substantial reductions in triglycerides and APOC3, with 90.6% of patients achieving a triglyceride level below the threshold linked to an increased risk of pancreatitis. Furthermore, 48.4% reached normal triglyceride levels.

Bruce Given, Arrowhead's interim chief medical scientist, expressed optimism regarding the 48-week data and announced the progression of the program into multiple Phase 3 studies, including SHASTA-3 and SHASTA-4, which are pivotal, year-long, placebo-controlled studies.

In terms of safety, plozasiran exhibited a favorable profile with adverse events comparable across treatment groups and reflective of the study population's comorbidities. The most common events were COVID-19 infection, worsening glycemic control, diarrhea, urinary tract infection, and headache.

SHASTA-2 was a double-blind, placebo-controlled Phase 2b study involving 229 participants with SHTG. The study aimed to evaluate the safety and efficacy of plozasiran and select a dosing regimen for later-stage clinical studies.

Severe hypertriglyceridemia is characterized by high triglyceride levels and significantly increases the risk of atherosclerotic cardiovascular disease and acute pancreatitis. Treatment options are limited, making the SHASTA-2 study's outcomes particularly noteworthy.

Plozasiran is an innovative RNA interference therapeutic designed to reduce the production of APOC3, a key regulator of triglyceride metabolism. The drug has shown promise in reducing triglycerides and atherogenic lipoproteins in various clinical studies and has been granted Orphan Drug Designation and Fast Track Designation by regulatory bodies.

Arrowhead Pharmaceuticals is dedicated to developing RNAi-based therapeutics that silence disease-causing genes, leveraging the body's natural gene silencing pathway to treat intractable diseases. The company's broad RNA chemistry portfolio and efficient delivery modes aim to induce rapid and durable knockdown of target genes.