FDA Approves Olezarsen as Adjunct to Diet for Familial Chylomicronemia Syndrome

The FDA approved olezarsen (Tryngolza; Ionis Pharmaceutical Inc) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). The rare genetic disease is a severe hypertriglyceridemia that can lead to potentially life-threatening acute pancreatitis.¹

FDA Approval, Familial Chyomicronemia Syndrome | Image Credit: Tyler Olson | stock.adobe.com

This makes it the first ever FDA-approved treatment that significantly and substantially reduces triglyceride levels in adults with FCS, according to the news release.¹

"Today's FDA approval of Tryngolza heralds the arrival of the first-ever FCS treatment in the US—a transformational moment for patients and their families. For the first time, adults with FCS can now access a treatment that substantially reduces triglycerides and the risk of debilitating and potentially life-threatening acute pancreatitis," Brett P. Monia, PhD, CEO of Ionis, said in a news release. " The FDA approval of Tryngolza is also a pivotal moment for Ionis, representing our evolution into a fully integrated commercial-stage biotechnology company—a goal we set out to achieve 5 years ago.”¹

The approval is based on data from the multicenter, randomized phase 3 Balance (NCT04568434) clinical trial. The study was a double-blinded trial with 60 patients with FCS. Treatment was randomized in a 2:1 ratio to receive either olezarsen or the placebo for the 53-week period. The study included an 8-week screening period, 53-week treatment period, and a 13-week post-treatment evaluation. Individuals were able to opt into an open-label extension study.²

Participants included individuals with genetically confirmed FCS, fasting triglycerides of 880 mg/dL or more at screening, and history of pancreatitis. Stable doses of statins, omega-3 fatty acids, fibrates, or lipid-lowering medications. Patients were excluded if they had acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, and other conditions that the investigators deemed unsuitable for inclusion.²

The primary outcome was the percent change from baseline in fasting triglycerides at 6 months compared with the placebo, and the secondary outcomes were percent change from baseline in fasting triglycerides at 12 months, percent change in fasting apoC-III from baseline at 6 and 12 months, change from baseline in the proportion of individuals who achieve 40% or greater reduction in fasting triglycerides at 6 months, and percentage change from baseline in fasting apoB-48 at 6 and 12 months.²

The results showed that the 80 mg dose had statistically significant placebo-adjusted mean reductions in triglycerides levels of 42.5% from baseline to 6 months, with a 57% mean reduction in triglycerides at 12 months. Further, only 1 individual experienced an acute pancreatitis episode in the study drug group compared with 7 patients experiencing 11 episodes in the placebo group.¹

Safety data showed that the most common adverse reactions were injection site reaction at 19% for the olezarsen group and 9% for the placebo group; decreased platelet count at 12% and 4%, respectively; and arthralgia at 9% and 0%, respectively.¹

"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," Alan Brown, MD, FNLA, FACC, FAHA, clinical professor of medicine at the Rosalind Franklin University of Medicine and Science, said in a news release. "The FDA approval of Tryngolza is an important moment for people living with FCS, 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."¹

REFERENCES

1. Tryngolza (olezarsen) approved in US as first-ever treatment for adults living with familial chylomicronemia syndrome as an adjunct to diet. News release. Ionis Pharmaceuticals Inc. December 19, 2024. Accessed December 20, 2024. https://prnmedia.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

2. A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS) (BALANCE). ClinicalTrials.gov ID: NCT04568434. December 13, 2024. Accessed December 20, 2024. https://clinicaltrials.gov/study/NCT04568434