Positive Phase 3 Results for Olezarsen in Treating Familial Chylomicronemia Syndrome

Ionis Pharmaceuticals has reported positive findings from their Phase 3 clinical trial of an investigational drug, olezarsen, intended for the treatment of familial chylomicronemia syndrome (FCS). This rare genetic disorder is characterized by extremely high triglyceride levels due to a dysfunction in the enzyme lipoprotein lipase (LPL), leading to the inability to break down chylomicrons effectively. The condition significantly increases the risk of acute pancreatitis and other health complications.

The Phase 3 Balance study, which involved 66 adult patients with genetically confirmed FCS, demonstrated that olezarsen, when administered at a dosage of 80 mg monthly, significantly reduced fasting triglyceride levels at the six-month mark. The drug also showed a substantial decrease in acute pancreatitis events over a 12-month period and maintained a favorable safety profile. The results were presented at the 2024 American College of Cardiology (ACC) Annual Meeting and published in The New England Journal of Medicine.

Erik Stroes, M.D., a principal investigator of the study and a professor of medicine at Amsterdam University Medical Centers, emphasized the importance of an effective therapy for FCS, which can alleviate chronic symptoms such as abdominal pain and cognitive issues, along with reducing hospitalizations due to acute pancreatitis.

In the trial, patients were given either 80 mg or 50 mg of olezarsen or a placebo every four weeks. The 80 mg dose of olezarsen not only met the primary endpoint but also sustained a 59% reduction in triglyceride levels from months six to twelve. The 50 mg dose, while reducing triglyceride levels, did not show a statistically significant difference compared to the placebo at six months. However, it improved to a 44% reduction from six to twelve months.

Significantly, patients treated with olezarsen experienced a marked reduction in acute pancreatitis events and hospitalizations. The drug also showed robust and sustained reductions in serum apolipoprotein C-III levels, a protein that plays a key role in triglyceride metabolism.

Brett P. Monia, Ph.D., CEO of Ionis, highlighted the significance of the study as the first to link reduced triglyceride levels with a decrease in acute pancreatitis events in patients with elevated triglycerides. He expressed optimism about the ongoing Phase 3 CORE studies evaluating olezarsen for severe hypertriglyceridemia and the potential for olezarsen to become a standard of care for FCS patients.

Ionis Pharmaceuticals, a company dedicated to inventing medicines for serious diseases, is now pursuing regulatory approval for olezarsen in the U.S., with the hope of providing the first FDA-approved therapy for FCS. The company also plans to host a webcast to discuss the study's detailed results.

Currently, there are no treatments approved by the U.S. FDA for FCS, and patients rely on strict dietary management to mitigate the health risks associated with the syndrome. Olezarsen, as an RNA-targeted investigational LICA medicine, is designed to inhibit the production of apoC-III, offering a new approach to managing the disease.

Ionis Pharmaceuticals has a history of innovation in RNA-targeted therapies and gene editing, with a goal to deliver life-changing advances for patients. The company's commitment to advancing new treatments is exemplified by their work on olezarsen and their ongoing studies in the field of cardiology and neurology.