Arrowhead's plozasiran promising for mixed hyperlipidemia

Arrowhead Pharmaceuticals revealed that their drug, plozasiran (previously known as ARO-APOC3), has shown significant promise in reducing triglyceride-rich lipoprotein levels in patients with mixed hyperlipidemia. This announcement came during the European Atherosclerosis Society (EAS) congress, with findings concurrently published in the New England Journal of Medicine (NEJM).

Plozasiran is being heralded as a potential treatment for various conditions with substantial unmet medical needs, including familial chylomicronemia syndrome, severe hypertriglyceridemia, and mixed hyperlipidemia, according to Bruce Given, the interim chief medical scientist at Arrowhead Pharmaceuticals. The company is planning to conduct more extensive clinical trials to further explore the efficacy of plozasiran.

The Phase IIb MUIR trial was a key study evaluating plozasiran's safety and efficacy. It involved 353 adult participants with mixed hyperlipidemia who were randomly assigned, in a 3:1 ratio, to receive subcutaneous injections of plozasiran at doses of 10mg, 25mg, or 50mg, or a placebo. These injections were administered on day 1 and at week 12, with an additional group receiving 50mg of plozasiran or a placebo on day 1 and at week 24.

The study's results were promising. By week 24, patients treated with plozasiran exhibited significant reductions in triglycerides and atherogenic triglyceride-rich lipoproteins, alongside increases in high-density lipoprotein cholesterol (HDL). Specifically, placebo-adjusted reductions in triglycerides were observed at -50%, -56%, and -62% for the 10mg, 25mg, and 50mg doses, respectively. Additionally, fasting triglyceride levels normalized in 79% to 92% of patients in the treatment arms. Corresponding reductions in apolipoprotein C-III (APOC3) were also noted: -57%, -73%, and -79%, demonstrating strong positive correlations with changes in triglyceride levels.

Plozasiran's safety profile was deemed favorable. The frequency of treatment-emergent adverse events (TEAEs) and the rate of discontinuations were comparable between the plozasiran and placebo groups throughout the 48-week observation period. Common TEAEs included COVID-19, worsening glycemic control, upper respiratory tract infections, urinary tract infections, headaches, and bronchitis.

Looking ahead, the principal investigator, Christie Ballantyne, expressed optimism about plozasiran's potential. The drug's ability to produce potent and durable reductions in atherogenic lipoproteins, such as non-HDL-C, ApoB, and remnant cholesterol, supports its further development in Phase III studies. These future studies will focus on patients with an increased risk of atherosclerotic cardiovascular disease, aiming to confirm the benefits observed in the Phase IIb trial.

In summary, Arrowhead Pharmaceuticals’ plozasiran has demonstrated significant efficacy in reducing triglyceride levels and improving lipid profiles in patients with mixed hyperlipidemia, with a favorable safety profile. These promising results pave the way for further research and potential future treatments for various lipid disorders and cardiovascular diseases.