BALANCE: Olezarsen for Familial Chylomicronemia Syndrome

Dr. Tashko specializes in chylomicron and triglyceride disorders, providing holistic care to Maryland patients with expertise in this area.

April 2024 NEJM

Background – Lipidologist in the State of Maryland

As a board-certified lipid specialist with extensive clinical and research experience, I place a strong emphasis on keeping current with the latest advancements. My goal is to provide our community with the highest standard of care, utilizing personalized and integrative approaches.

Conveniently located in Rockville, my practice offers virtual and in-person services, extending support to nearby areas such as Chevy Chase, Bethesda, North Bethesda, Potomac, North Potomac, Gaithersburg, Germantown, Frederick, Silver Spring, Northern Virginia, Howard County, Anne Arundel, and the Eastern Shore of Maryland, ensuring comprehensive care.

Here, I provide a summary of the BALANCE study, which showcases the benefits of reducing apolipoprotein C-III in individuals with Familial Chylomicronemia Syndrome. We’ll delve into the key findings and results published in the New England Journal of Medicine in April 2024.

Olezarsen Shows Promise in Reducing Triglycerides and Pancreatitis Risk in Familial Chylomicronemia Syndrome

The BALANCE trial investigated the effectiveness of olezarsen, a new drug, in treating familial chylomicronemia syndrome (FCS). FCS is a rare genetic disorder causing extremely high triglyceride levels in the blood, which can lead to severe pancreatitis, inflammation of the pancreas.

Background on Olezarsen 

Olezarsen is an investigational drug that tackles triglycerides by blocking the production of apolipoprotein C-III (apoC3). ApoC3 normally hinders the liver’s ability to remove triglycerides from the blood. By reducing apoC3, Olezarsen allows the liver to work more effectively, lowering triglyceride levels. This can significantly reduce the risk of pancreatitis, a dangerous condition caused by high triglyceride levels in the blood.

Study Design:

  • Researchers conducted a phase 3, double-blind, placebo-controlled trial. This means neither patients nor researchers knew who received the drug or placebo until the end.
  • Approximately 60 patients with genetically confirmed FCS participated.
  • Patients (20 in each arm) were randomly assigned to receive:
    • Olezarsen at a high dose (80mg)
    • Olezarsen at a lower dose (50mg)
    • Placebo
  • All groups received injections under the skin every 4 weeks for 53 weeks.
  • The primary endpoint aimed to see how much olezarsen could reduce triglyceride levels compared to placebo, with a secondary focus on reducing pancreatitis episodes.

Results:

  • Patients had very high triglyceride levels at baseline (average 2,630 mg/dL) and a history of pancreatitis in 71% of cases.
  • After 6 months, the high-dose olezarsen group showed a significant decrease in triglycerides (43.5% reduction) compared to placebo. The lower dose did not show a statistically significant reduction.
  • Both olezarsen doses significantly decreased apolipoprotein C-III levels, a protein involved in fat metabolism.
  • Over the entire study period, the placebo group experienced 11 pancreatitis episodes, whereas each olezarsen group had only 1 episode. This suggests a potential reduction in pancreatitis risk with olezarsen.
  • Some moderate side effects possibly related to the drug were reported in the high-dose olezarsen group.

Summary:

The BALANCE trial suggests that olezarsen, particularly at the higher dose, could be a valuable new treatment for FCS. It effectively lowers triglycerides, potentially reducing the risk of severe pancreatitis, a major complication of FCS. However, further research is needed to confirm these findings and assess long-term safety of the drug.

Dr. Tashko