Action
The U.S. Food and Drug Administration has approved Tryngolza (olezarsen), used with diet, to reduce triglycerides (TG) in adults with familial chylomicronemia syndrome (FCS). This is a first-in-class approval, meaning Tryngolza uses a new mechanism of action, or works differently in the body, than other therapies currently used to treat FCS.
Tryngolza is injected subcutaneously (under the skin) once per month.
Disease or Condition
FCS is a rare, genetic disorder that prevents the body from breaking down fats (TG) in the bloodstream. Normal TG levels are less than 150 mg/dL and 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 and safety of Tryngolza were evaluated in a randomized, placebo-controlled, double-blind clinical trial (NCT04568434) in 66 adult patients with FCS and fasting TG levels of at least 880 mg/dL (the average baseline TG level was approximately 2600 mg/dL). The primary endpoint was percent change in fasting TG levels from baseline to month 6 (average of weeks 23, 25, and 27) compared to placebo.
The average percent change in TG from baseline to month 6 in the Tryngolza treatment group was -42.5% compared to the placebo group. Median percent and absolute changes in TG levels from baseline over time demonstrated a consistent lowering effect during the 12-month treatment period.
Safety Information
Hypersensitivity reactions (including symptoms of chest tightness and shortness of breath, redness of the skin, chills, and muscle pain and tenderness) have been reported in patients treated with Tryngolza. Health care providers should advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of Tryngolza if these should occur.
The most common adverse reactions in patients treated with Tryngolza were injection site reactions, decreased platelet count, and joint pain or stiffness (arthralgia).
Designations
Tryngolza received Priority Review, Fast Track, Breakthrough Therapy, and Orphan Drug designations for this indication.
