FDA Approves Plozasiran for Triglyceride Reduction in Familial Chylomicronemia Syndrome

The US Food and Drug Administration has approved FDA Plozasiran for Triglyceride Reduction in Familial Chylomicronemia Syndrome. Plozasiran is (Redemplo), an siRNA-based therapy that lowers triglycerides by inhibiting apolipoprotein C-III production. It is now indicated as a diet-adjunct treatment for adults with familial chylomicronemia syndrome (FCS), a rare genetic disorder that impairs the breakdown of triglycerides.

Disease or Condition

FCS is a rare genetic disorder that affects the body's ability to break down fats (triglycerides (TGs)) in the bloodstream. This leads to abnormally high levels of chylomicrons, which are particles that carry triglycerides. Normal TG levels are less than 150 mg/dL; levels above 500 mg/dL are considered severely high (severe hypertriglyceridemia). People with FCS can have TG levels in the thousands. These high TG levels can cause severe abdominal pain, inflammation of the pancreas (acute pancreatitis), and fatty deposits in the skin (xanthomas). Some of these symptoms, specifically acute pancreatitis, can be life-threatening.

For those with FCS, symptoms can develop in infancy, but some patients may not experience symptoms until they are adults. FCS has an estimated prevalence of 1 to 10 per 1,000,000 people.

Effectiveness

The efficacy of Redemplo was demonstrated in a randomized, placebo-controlled, double-blind trial (NCT05089084) in adults with genetically confirmed or clinically diagnosed FCS maintained on a low-fat diet (≤20 grams fat per day). Patients were randomly assigned to receive four total doses of Redemplo 25 mg or matching placebo, injected subcutaneously (under the skin) once every three months over a 12-month treatment period. The primary endpoint was percent change in fasting TGs from baseline to month 10. The median percent change in TG from baseline to month 10 in the Redemplo treatment group was -59% compared to the placebo group.

Redemplo is administered as a 25 mg injection once every three months into the front of the thigh or abdomen. The outer area of the upper arm can be used as an injection site if a health care provider or caregiver administers the injection.

Safety Information

The most common side effects are hyperglycemia (high blood sugar), headache, nausea, and injection site reaction.