Ionis Pharmaceuticals (IONS) Phase 3 study of olezarsen in people with familial chylomicronemia syndrome met its primary endpoint

September 26, 2023 7:01 AM EDT

Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive topline results for the Phase 3 Balance study of olezarsen in people with familial chylomicronemia syndrome (FCS). The trial met its primary efficacy endpoint with a statistically significant reduction in triglyceride (TG) levels with the olezarsen 80 mg monthly dose at six months compared to placebo (p=0.0009); triglyceride lowering continued to improve at 12 months. In addition, olezarsen 80 mg showed a 100 percent reduction in acute pancreatitis events compared to placebo (0 events for olezarsen versus 11 events for placebo), a key secondary endpoint.

Treatment with olezarsen 80 mg resulted in a >75% reduction in apoC-III, a protein produced in the liver that regulates TG metabolism in the blood. In addition to the 80 mg monthly dose, the study also evaluated a lower 50 mg monthly dose. Olezarsen demonstrated a dose-dependent effect, with both study doses showing a substantial reduction in pancreatitis. The lower 50 mg dose did not reach statistical significance at six months on the primary endpoint of triglyceride lowering (p=0.0775).

Ionis plans to file a New Drug Application in early 2024 with the U.S. Food and Drug Administration (FDA) in addition to EU regulatory filings. If approved, olezarsen would be the first available treatment in the U.S. for FCS, a rare, debilitating genetic disease that can lead to acute, potentially fatal pancreatitis attacks. The FDA granted olezarsen Fast Track designation for the treatment of FCS in 2023, which is designed to expedite the FDA's review of innovative, new drugs that demonstrate the potential to address unmet medical need. Ionis will present the Phase 3 olezarsen FCS data at a future medical congress.

"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. 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," said Sam Tsimikas, M.D., senior vice president, global cardiovascular development at Ionis. "In this study, people with FCS treated with olezarsen along with background therapy and a low-fat diet had a substantially reduced risk of recurrent attacks of acute pancreatitis. These results strengthen our confidence in olezarsen's potential to deliver benefits to FCS patients and in the larger population with SHTG following completion of ongoing Phase 3 studies."

Olezarsen demonstrated a favorable safety and tolerability profile in the study. There were more adverse events in the placebo group compared to the olezarsen groups, primarily due to pancreatitis events. The majority of adverse events in the olezarsen groups were mild in severity. There was a low incidence of injection site reactions. No hepatic or renal toxicity events occurred and there were no clinically meaningful platelet reductions. One death was reported in the study, which was deemed as not related to study drug.

"Today is a proud moment in our company's evolution, as olezarsen is poised to be a long-awaited advance for FCS patients and Ionis' first potential independent commercial launch," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We believe olezarsen has the potential to become the new standard of care for patients with FCS and we are excited about its potential in the broader population of patients with SHTG where we have ongoing pivotal trials. We want to express our gratitude to the patients, caregivers, investigators and study teams who participated in the Balance study. We look forward to submitting these data to the FDA and anticipate that olezarsen will be the first of many medicines from our wholly owned pipeline that we bring to people with debilitating diseases."


Ionis will conduct a webcast today at 11:00 a.m. Eastern time to discuss this announcement. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. Visit for more information and to register.

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