What Is Plozasiran?
Plozasiran is an investigational drug, also known by its study name ARO-APOC3. It is administered as a subcutaneous injection. Plozasiran is designed to target apolipoprotein C-III (APOC3), a protein that plays a key role in regulating triglyceride levels in the blood. By reducing the production of APOC3, plozasiran aims to lower very high triglyceride levels, which can contribute to various health issues.
Currently, plozasiran is not approved by regulatory bodies but is being studied in clinical trials for its potential to treat conditions involving significantly elevated triglycerides. Researchers are investigating its use for severe hypertriglyceridemia and familial chylomicronemia syndrome, among other related conditions. A total of 8 clinical trials have been conducted or are currently underway for plozasiran, enrolling a total of 3,482 participants. These trials began with the first study in 2021 and include studies initiated as late as 2025. Of these, 2 trials are currently recruiting participants, and 1 trial has been completed.
Uses and Conditions Under Study
Plozasiran is being investigated for its potential to treat conditions characterized by abnormally high levels of triglycerides in the blood. These conditions can increase the risk of pancreatitis and other cardiovascular issues.
One primary area of study for plozasiran is Hypertriglyceridemia, including Severe Hypertriglyceridemia and High Risk Severe Hypertriglyceridemia (SHTG). Hypertriglyceridemia refers to having too many triglycerides, a type of fat, in the blood. Severe forms can lead to serious health complications. Plozasiran aims to reduce these high triglyceride levels by targeting APOC3. A total of 6 trials are investigating plozasiran for various forms of hypertriglyceridemia.
Another key focus is Familial Chylomicronemia Syndrome (FCS), sometimes referred to as Familial Chylomicronemia. FCS is a rare genetic disorder characterized by extremely high triglyceride levels due to the body's inability to properly break down fats called chylomicrons. This condition can lead to recurrent episodes of severe abdominal pain and pancreatitis. Plozasiran's mechanism of reducing APOC3 is being explored as a way to help manage these dangerously high triglyceride levels in patients with FCS. Plozasiran is being studied in 3 trials specifically for familial chylomicronemia or familial chylomicronemia syndrome.
Dosing
Plozasiran is administered as an injection. The specific dosage forms studied in clinical trials include Plozasiran Injection and ARO-APOC3 (Plozasiran). It is given as a subcutaneous injection, meaning it is injected under the skin.
Clinical trials have investigated different strengths of plozasiran to determine the most effective and safe dose. The strengths studied include Plozasiran 25 mg and Plozasiran 50 mg. These strengths have been explored across the various conditions under investigation, such as severe hypertriglyceridemia and familial chylomicronemia syndrome. The exact frequency of administration (e.g., once daily, weekly, or monthly) is determined within each specific clinical trial protocol and is not detailed in the general drug data.
For comparison in studies, a placebo has also been used. There is no information available regarding specific pediatric doses or different dosing regimens for various conditions, as these details are typically part of individual trial designs.
Side Effects
In clinical trials, the most common side effects reported with Plozasiran included:
- Increased alanine aminotransferase (a liver enzyme), which occurred in 25.0% of patients taking Plozasiran, compared to 7.7% on placebo.
- Influenza-like illness, experienced by 25.0% of patients taking Plozasiran, compared to 15.4% on placebo.
- Abdominal pain, reported by 23.0% of patients taking Plozasiran, compared to 18.4% on placebo.
- Upper respiratory tract infection, affecting 14.9% of patients taking Plozasiran, compared to 7.9% on placebo.
- Nausea, which occurred in 14.0% of patients taking Plozasiran, compared to 8.0% on placebo.
- Increased glycosylated hemoglobin, seen in 12.0% of patients taking Plozasiran, compared to 0.0% on placebo.
Other side effects reported at rates of 10.8% or less included headache (10.8% with Plozasiran vs 7.9% with placebo), diarrhea (10.8% with Plozasiran vs 5.3% with placebo), nasopharyngitis (10.8% with Plozasiran vs 10.5%
Currently Recruiting Trials
Plozasiran is currently being investigated in clinical trials to understand its potential in managing hypertriglyceridemia, a condition characterized by high levels of triglycerides in the blood. These studies aim to evaluate both the effectiveness and safety of this investigational treatment.
One active study, NCT06880770, is a Phase 3 trial sponsored by Arrowhead Pharmaceuticals. This study is evaluating plozasiran in adults with severe hypertriglyceridemia (SHTG) who are at risk of acute pancreatitis. Participants must have a history of at least two prior acute pancreatitis events not attributed to other causes, with at least one occurring within the last 12 months. The trial is designed to enroll approximately 288 adult participants and compares plozasiran injections to a placebo.
Another Phase 3 trial, NCT06822790, is an open-label study also sponsored by Arrowhead Pharmaceuticals. This trial focuses on the long-term safety and efficacy of plozasiran in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG). This study is specifically for participants who have completed all required visits in a previous "parent study," such as AROAPOC3-2003 (USA and Canada participants only; NCT05413135) or AROAPOC3-3001. This trial aims to enroll approximately 869 participants.
Where to Participate
Opportunities to participate in plozasiran clinical trials are available across a wide geographic area. These studies are being conducted at 80 sites across 66 cities in 21 states, offering many potential locations for interested individuals.
Top participating locations include:
- Houston, Texas (5 sites)
- St Louis, Missouri (2 sites)
- Summit, New Jersey (2 sites)
- Indianapolis, Indiana (2 sites)
- Philadelphia, Pennsylvania (2 sites)
- Orlando, Florida (2 sites)
- Wilmington, North Carolina (2 sites)
- New York, New York (2 sites)
- Norman, Oklahoma (2 sites)
- Baltimore, Maryland (2 sites)
To be eligible for these trials, participants must be at least 18 years old. The studies are open to all genders, but they are not seeking healthy volunteers and do not include children.
Development Timeline
The development journey for plozasiran began with its first clinical trial on October 22, 2021, primarily driven by Arrowhead Pharmaceuticals. Initially, the investigational drug explored potential applications for conditions such as IBS-C (irritable bowel syndrome with constipation) and hyperphosphatemia. However, the focus of the development program soon expanded.
Over time, the pipeline for plozasiran grew to include hypertriglyceridemia, Familial Chylomicronemia Syndrome, and High Risk Severe Hypertriglyceridemia (SHTG), reflecting an evolving understanding of the drug's potential. The majority of plozasiran's clinical studies have progressed to Phase 3, indicating advanced stages of research. While Arrowhead Pharmaceuticals has sponsored 7 of the trials, one study was sponsored by Visirna Therapeutics HK Limited.
To date, a total of 8 clinical trials for plozasiran have been initiated, with a combined enrollment of 3,482 participants. The latest trial is projected to conclude by March 18, 2025, continuing the effort to bring this potential treatment to patients.