First Drug Approved for Familial Chylomicronemia Syndrome

The FDA approved olezarsen (Tryngolza) as the first drug for adults with familial chylomicronemia syndrome, a rare genetic disorder that can cause triglyceride levels to reach the thousands.

A first-in-class antisense oligonucleotide, olezarsen is indicated in conjunction with a low-fat diet.

Approval was supported by the phase III Balance trial, which involved 66 patients with severe hypertriglyceridemia as a result of their condition. Administered subcutaneously once a month, olezarsen at an 80-mg dose reduced plasma triglyceride levels by 42.5 percentage points compared with placebo at 6 months (95% CI -74.1 to -10.9, P=0.0084). Baseline triglycerides averaged about 2,600 mg/dL (normal ranges are below 150 mg/dL). Olezarsen also led to a clinically meaningful reduction in acute pancreatitis events.

“With no treatment options previously available, we were limited to relying only on extremely strict diet and lifestyle changes as the sole preventative treatment option,” said investigator Alan Brown, MD, of the Rosalind Franklin University of Medicine and Science in North Chicago, in a statement from developer Ionis Pharmaceuticals.

“The FDA approval of Tryngolza is an important moment for people living with [familial chylomicronemia syndrome], their families, and physicians who now, for the first time, have a treatment that significantly lowers triglycerides and decreases the risk of potentially life-threatening acute pancreatitis events, as an adjunct to a low-fat diet.”

“I am excited to have a medicine I can prescribe to my patients that has been shown to change the course of their disease,” he added.

Impacting an estimated 1 to 10 per million people, familial chylomicronemia syndrome is a rare form of severe hypertriglyceridemia that prevents the body from breaking down and removing triglycerides from the bloodstream due to an impaired function of the enzyme lipoprotein lipase. This can lead to severe abdominal pain, xanthomas, and acute pancreatitis, which can be potentially life-threatening.

Olezarsen is an mRNA-targeted ligand conjugated antisense medicine that works by lowering the body’s production of apolipoprotein C-III, a key regulator of triglyceride metabolism.

Common adverse events in the Balance trial with olezarsen included injection site reactions (19%), decreased platelet count (12%), and arthralgia (9%), according to the prescribing information. Some cases of hypersensitivity reactions, including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias were also reported. Patients should promptly seek medical attention and discontinue use if this occurs.

Olezarsen will be available in the U.S. before the end of the year, said Ionis.

In addition to familial chylomicronemia syndrome, the antisense oligonucleotide is also currently being evaluated in three phase III trials of severe hypertriglyceridemia.