FDA Grants Breakthrough Therapy Status to Arrowhead's Plozasiran

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) announced that the FDA has granted Breakthrough Therapy designation to its investigational drug, plozasiran, which aims to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). FCS is a severe genetic condition marked by very high levels of triglycerides, leading to acute and potentially fatal pancreatitis. Currently, there are no approved treatments for FCS in the United States.

Chris Anzalone, Ph.D., President and CEO of Arrowhead, emphasized the lack of FDA-approved therapies for FCS, highlighting the need for new treatment options. He noted that clinical studies of plozasiran have shown promising results, making a strong case for further development and commercialization. The FDA's Breakthrough Therapy designation is expected to expedite the drug's development and review process, potentially accelerating its availability to patients.

The Breakthrough Therapy designation is intended to speed up the development and review process for drugs that treat serious conditions and show substantial improvement over existing therapies based on preliminary clinical evidence. Plozasiran has also received Orphan Drug Designation and Fast Track Designation from the FDA, as well as Orphan Drug Designation from the European Medicines Agency. Arrowhead plans to submit a New Drug Application to the FDA by the end of 2024 and seeks to gain regulatory approval from other global authorities subsequently.

Familial chylomicronemia syndrome (FCS) is a rare and severe genetic disorder often caused by various monogenic mutations. It results in extremely high triglyceride levels, usually exceeding 880 mg/dL. These elevated levels can lead to several serious health issues, including acute pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive problems. Current treatment options for FCS are limited and inadequate.

Plozasiran, previously known as ARO-APOC3, is a pioneering RNA interference (RNAi) therapeutic designed to reduce the production of apolipoprotein C-III (APOC3), a component of triglyceride-rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases blood triglyceride levels by inhibiting the breakdown of TRLs and the uptake of TRL remnants by hepatic receptors in the liver. The aim of plozasiran treatment is to lower APOC3 levels, thereby reducing triglycerides and normalizing lipid levels.

Clinical studies have shown that plozasiran effectively reduces triglycerides and multiple atherogenic lipoproteins in patients with FCS, severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. The drug has demonstrated a favorable safety profile, with reported adverse events generally reflecting the underlying conditions of the study populations.

Plozasiran is currently under investigation in the SUMMIT program of clinical studies, which includes the PALISADE Phase 3 study for FCS patients. This study recently completed, along with other studies focusing on SHTG and mixed hyperlipidemia. Arrowhead aims to file a New Drug Application with the FDA in 2024 and to seek additional regulatory approvals globally. It is important to note that plozasiran has not yet been reviewed or approved for treating any disease.

The PALISADE study (NCT05089084) is a Phase 3, placebo-controlled investigation evaluating the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint is the percentage change from baseline in fasting triglycerides versus placebo at Month 10. A total of 75 subjects across 39 sites in 18 countries were randomized to receive different doses of plozasiran or a matching placebo every three months. Participants who completed the randomized period were eligible for an extension period where all received plozasiran.

Arrowhead is dedicated to bringing new investigational medicines to patients with serious diseases as quickly as possible. The company has established an expanded access program (EAP) for individuals with FCS. As with any investigational medicine not yet approved by regulatory authorities, plozasiran may or may not be effective, and there may be risks associated with its use. Patients and caregivers are encouraged to discuss treatment options with their physicians.

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