ARO-APOC3 Trial Begins for Mixed Dyslipidemia


In a news release from September 30, 2021, biopharmaceutical company Arrowhead Pharmaceuticals (“Arrowhead”) shared that it had initiated its Phase 2b AROAPOC3-2002 clinical trial and that the first patient had been dosed. This clinical trial seeks to evaluate ARO-APOC3 for adult patients with mixed dyslipidemia.


So what exactly is ARO-APOC3? According to Arrowhead, ARO-APOC3 is a subcutaneously administered therapy:

…Designed to reduce production of Apolipoprotein C-III (apoC-III), a component of triglyceride rich lipoproteins (TRLs) including VLDL and chylomicrons and is a key regulator of triglyceride metabolism. The company believes that knocking down the hepatic production of apoC-III may result in reduced VLDL synthesis and assembly, enhanced breakdown of TRLs, and better clearance of VLDL and chylomicron remnants.

Within this particular trial, researchers are evaluating the safety, efficacy, and tolerability of ARO-APOC3 for patients with mixed dyslipidemia. Altogether, 320 patients will enroll. Patients will be split into 4 cohorts. Of these, one cohort will receive a placebo, another 10mg ARO-APOC3, another 25mg, then 50mg. These cohorts are dependent on triglyceride and LDL and HDL counts upon enrollment.

Outside of mixed dyslipidemia, Arrowhead is also exploring ARO-APOC3 as a potential therapeutic option for patients with familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG) in various other clinical trials.

Mixed Dyslipidemia

Dyslipidemia occurs when patients have blood lipid levels, like cholesterol or triglycerides, which are either too high or too low. According to MedScape, mixed dyslipidemia is:

defined as elevations in LDL cholesterol and triglyceride (TG) levels that are often accompanied by low levels of HDL cholesterol. Previously, the combination of high LDL cholesterol and TG was classified under the heading of combined hyperlipidemia.

While a number of genetic mutations have been associated with mixed dyslipidemia, it may also be idiopathic (without a known cause). Additionally, risk factors include type 2 diabetes, being overweight, having high blood pressure or nonalcoholic fatty liver disease (NAFLD), alcoholism, or having hypothyroidism. Mixed dyslipidemia can cause impaired blood flow or unhealthy lipid levels in the blood, raising the risk of developing additional conditions such as coronary artery disease.

While many people may not have symptoms at first, symptoms which do appear include:

  • Chest pain
  • Toe sores which fail to heal
  • Calf cramping which worsens when walking
  • A sudden onset of:
    • Difficulty speaking
    • Drooping on one side of the face
    • Arm or leg weakness
    • Balance loss
    Jessica Lynn

    Jessica Lynn

    Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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