Arrowhead's cholesterol drug succeeds in phase 2 hyperlipidemia trial

Arrowhead Pharmaceuticals is making promising strides with its new drug, plozasiran, which has shown significant potential in treating various forms of dyslipidemia—a condition characterized by abnormal levels of lipids or lipoproteins in the blood, often associated with an increased risk of cardiovascular diseases. Analysts are optimistic about the drug's commercial prospects, projecting that it could generate $707 million in sales by 2032.

Plozasiran's efficacy was highlighted in a phase 2 trial, known as the MUIR study, the results of which were presented at the 92nd European Atherosclerosis Society Congress and published in The New England Journal of Medicine. The drug demonstrated its ability to lower key lipoproteins that contribute to cardiovascular risks in patients with mixed hyperlipidemia, a condition marked by elevated levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides.

Traditional treatments for these patients typically involve LDL-C-lowering therapies to mitigate atherosclerotic cardiovascular disease risks. However, these treatments often fall short for those with elevated non-high-density lipoprotein cholesterol (non-HDL-C). Plozasiran addresses this gap by reducing atherogenic lipoproteins, including non-HDL-C, ApoB, and remnant cholesterol.

The MUIR study's findings were encouraging. After administering two quarterly doses of plozasiran by Week 24, patients experienced significant reductions in triglyceride levels—50%, 56%, and 62% reductions at the 10-, 25-, and 50-mg doses, respectively. Furthermore, fasting triglyceride levels normalized in 79% to 92% of patients, depending on the treatment arm.

Safety is always a paramount concern with new therapies, and plozasiran showed a favorable safety profile. The incidence of treatment-emergent adverse events and discontinuations was comparable between the treatment and placebo groups, suggesting that the drug is generally well-tolerated.

Plozasiran, formerly known as ARO-APOC3, is an RNA interference therapy designed to reduce the production of apolipoprotein C-III (APOC3). APOC3 is a protein involved in triglyceride metabolism and is a component of triglyceride-rich lipoproteins. By targeting APOC3, the drug aims to lower triglyceride levels and restore lipid levels to normal, thereby reducing the risk of atherosclerosis.

The U.S. Food and Drug Administration (FDA) has recognized the potential of plozasiran by granting it orphan-drug and fast-track designations. In addition, it has received orphan-drug designation in Europe, which could expedite its development and approval processes.

In addition to the MUIR study, Arrowhead Pharmaceuticals has also released data from the SHASTA-2 study, a midstage trial focusing on severe hypertriglyceridemia. Results from this study showed that plozasiran improved outcomes at Week 48, significantly lowering triglycerides and other associated biomarkers.

Currently, plozasiran is undergoing phase 3 trials for multiple indications, further solidifying its potential role in treating various dyslipidemia conditions. Christie Ballantyne, M.D., the principal investigator of the MUIR study and a professor at the Baylor College of Medicine, emphasized that the latest results strongly support advancing to late-stage clinical development.

With its promising clinical trial results and significant market potential, plozasiran could become a major player in the treatment of cholesterol disorders, offering hope to patients who have limited options with existing therapies. Arrowhead Pharmaceuticals' continued research and development efforts will be crucial in bringing this innovative therapy to market and improving the lives of individuals with dyslipidemia.