Familial chylomicronemia syndrome (FCS) is an autosomal recessive metabolic disease that is associated with hypertriglyceridemia where the patients cannot metabolize the chylomicrons. It is a potentially dangerous condition, which can also be evident as severe pain in the abdomen, fatigue, and multiple episodes of acute pancreatitis (AP), which is an acute inflammation of the pancreas.
TRYNGOLZA™ (olezarsen) was approved by the U.S. Food and Drug Administration (FDA) on December 19, 2024, by Ionis Pharmaceuticals. This approval breakthrough is the first time that FCS adults have a treatment option. TRYNGOLZA is used in these patients as an added treatment to diet to help manage the triglyceride levels and there is evidence from some earlier studies that there was a reduction in the rate of AP occurrences.
The approval of TRYNGOLZA is based on data from the global phase 3 balance clinical trial, a multicentre, placebo-controlled, double-blind study. The trial involved participants who met the following inclusion criteria; adult patients with genetically confirmed FCS and fasting triglyceride concentrations ≥ 880 mg/dL. The participants took TRYNGOLZA 80mg monthly using an auto-injector while following a low-fat diet of less than 20 gm of fat daily. The primary outcome measure was the percent change in the triglyceride level from baseline to six months of follow-up the secondary outcomes included a comparison of the triglyceride levels at twelve months and the occurrence of AP episodes either at six or at twelve months of the trial.
Analyzing data obtained in the balance study, it was found that patients receiving TRYNGOLZA had their triglyceride levels decreased with statistical significance. At the end of six months, the mean percentage reduction in triglycerides from placebo control was 42.5% (p = 0.0084); and after one year of treatment, the mean percentage reduction in triglycerides was 57%. Furthermore, considering the number of patients with at least one episode of AP, the TRYNGOLZA treatment was statistically significantly less compared to the placebo, with 5% of patients in the TRYNGOLZA group reporting 11 episodes of AP against 30% of the placebo group patients.
According to safety data, TRYNGOLZA is well tolerated with no significant safety concerns. The three main side effects were injection reactions, which were reported in 19% of the patients in the treatment group and 9% of those in the placebo group, low platelet count was noted in 12% of the patients in the treatment group, and in the 4% of the placebo group, and arthralgia, which affected 9% of the patients in the treatment group and none in the placebo group.
FCS is a rare and frequently unrecognized that may lead to significant morbidity such as recurrent attacks of AP, chronic abdominal pain, and fatigue. Until now, there were no other management options besides very rigid dieting and monitoring of carbohydrate intake. The approval of TRYNGOLZA provides a new way to treat this severe disease which has a great impact on patients’ lives.
TRYNGOLZA has therefore been shown to have a relatively good safety profile, particularly when common injection site problems and mild effects in platelet count are considered. This approval is a revolution in the management of FCS patients as it will enable them to take a medicine that targets the core of the problem.
The approval of TRYNGOLZA by the FDA can thus be considered a very important step for the FCS community and the health-related systems. Adult FCS patients have a new, specific therapy that dramatically decreases triglyceride levels and the risk of life-threatening AP. TRYNGOLZA is the first of several groundbreaking drugs to both address the unique needs of people with severe hypertriglyceridemia and create more options for therapies targeting rare diseases in the future. Based on constant clinical trials, the company, and its commitment to patients, Ionis Pharmaceuticals continues to position itself for the future of rare disease treatment.
References: Ionis Pharmaceuticals, Inc. TRYNGOLZA™ (olezarsen) approved in U.S. as first-ever treatment for adults living with familial chylomicronemia syndrome as an adjunct to diet. PR Newswire. Published December 19, 2024. https://www.prnewswire.com/news-releases/tryngolza-olezarsen-approved-in-us-as-first-ever-treatment-for-adults-living-with-familial-chylomicronemia-syndrome-as-an-adjunct-to-diet-302336747.html
