Olezarsen Benefits Familial Chylomicronemia Syndrome in Phase 3 Balance Trial


Announced by Ionis Pharmaceuticals, topline results show olezarsen met the study's primary endpoint with a statistically significant reduction in triglyceride levels versus placebo.

Sam Tsimikas, MD | Image Credit: Ionis Pharmaceuticals

Sam Tsimikas, MD

Credit: Ionis Pharmaceuticals

New phase 3 topline results indicate olezarsen met its primary endpoint in people with familial chylomicronemia syndrome (FCS), a rare, debilitating genetic disease that can lead to acute pancreatitis attacks.1

Announced by Ionis Pharmaceuticals on September 26, treatment with olezarsen 80 mg led to a statistically significant reduction in triglyceride levels versus placebo, as well as an absolute reduction in acute pancreatitis, in the phase 3 Balance trial.

“These positive olezarsen topline results represent an important advance for people with FCS who live in constant fear of unpredictable and potentially fatal attacks of acute pancreatitis,” said Sam Tsimikas, MD, senior vice president, global cardiovascular development, Ionis.1 “With no currently FDA-approved treatments, people with FCS live with debilitating abdominal pain and must maintain an extremely restrictive diet consisting of less than 20 grams of fat per day.”

The Balance study, a global, multicenter, randomized, double-blind, placebo-controlled phase 3 trial, enrolled patients 18 years and older with confirmed FCS. Patients were randomized in a 1:1:1 ratio to receive olezarsen 80 mg or 50 mg or placebo via subcutaneous injection once every 4 weeks for 53 weeks.

Meeting its primary efficacy endpoint, the trial showed a statistically significant reduction in triglyceride levels with olezarsen 80 mg monthly at 6 months compared to placebo (P = .0009), with triglyceride lowering continuing to improve at 12 months. Regarding key secondary endpoints, olezarsen 80 mg showed a 100% reduction in acute pancreatitis events at 0 events, compared to 11 events for placebo. Treatment with olezarsen 80 mg was associated with a greater than 75% reduction in apoC-III.

A lower 50 mg monthly dose of olezarsen was also studied in the Balance study. The agent demonstrated a dose-dependent effect, with both study doses (50 mg and 80 mg) showing a substantial reduction in pancreatitis. However, the 50 mg dose did not reach statistical significance at 6 months for the primary endpoint of triglyceride-lowering (P = .0775).

The therapy showed a favorable safety and tolerability profile in the study results. More adverse events were identified in the placebo group, compared to the olezarsen groups, and were primarily related to pancreatitis events. Most adverse events in the olezarsen groups were mild in severity and there was a low incidence of injection site reactions.

In addition, no hepatic or renal toxicity events were identified, as well as no clinically meaningful platelet reductions. A single death was reported in the study and was considered unrelated to the study drug.

“In this study, people with FCS treated with olezarsen along with background therapy and a low-fat diet had substantially reduced risk of recurrent attacks of acute pancreatitis,” Tsimikas said.1 “These results strengthen our confidence in olezarsen’s potential to deliver benefits to FCS patients and in the larger population with severe hypertriglyceridemia following completion of ongoing phase 3 studies.”

The company plans to file a New Drug Application (NDA) with the US Food and Drug Administration (FDA) in early 2024, in addition to regulatory filings in the European Union. If approved, olezarsen would be the first available treatment in the US for the rare genetic disease. The FDA previously granted olezarsen Fast Track designation in 2023.2


  1. Ionis announces positive olezarsen topline results from phase 3 study in people with familial chylomicronemia syndrome. Ionis Pharmaceuticals, Inc. September 26, 2023. Accessed September 26, 2023. https://ir.ionispharma.com/news-releases/news-release-details/ionis-announces-positive-olezarsen-topline-results-phase-3-study.
  2. Ionis receives FDA Fast Track designation for Olezarsen in patients with familial chylomicronemia syndrome. Ionis Pharmaceuticals, Inc. January 31, 2023. Accessed September 26, 2023. https://ir.ionispharma.com/news-releases/news-release-details/ionis-receives-fda-fast-track-designation-olezarsen-patients.
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