Ionis Reports Positive Phase 3 Results for FCS Therapy

Ionis Reports Positive Phase 3 Results for FCS Therapy

Rare Daily Staff

Ionis Pharmaceuticals reported positive topline results for the phase 3 Balance study of olezarsen, its experimental therapy for people with the rare lipoprotein condition familial chylomicronemia syndrome.

The trial met its primary efficacy endpoint with a statistically significant reduction in triglyceride levels with the olezarsen 80 mg monthly dose at six months compared to placebo. 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, a key secondary endpoint.

Familial chylomicronemia syndrome FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot break down chylomicrons, lipoprotein particles that are 90 percent triglycerides. FCS is estimated to impact 1-2 people per million worldwide. People living with FCS are at high risk for acute pancreatitis in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. They are sometimes unable to work, adding to their disease burden.

Olezarsen is an experimental lIgand conjugated antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride (TG) levels including those with familial chylomicronemia syndrome, or FCS. Olezarsen is designed to inhibit the body’s production of apoC-III, a protein produced in the liver that regulates TG metabolism in the blood. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (SHTG) in phase 3 clinical trials.

Treatment with olezarsen 80 mg resulted in a greater than 75 percent 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.

Currently, there are no FDA-approved therapies for the treatment of FCS. People living with this condition currently rely solely on nutrition management through extremely restrictive diets to navigate the health risks associated with FCS.

Ionis plans to file a New Drug Application in early 2024 with the U.S. Food and Drug Administration in addition to EU regulatory filings. If approved, olezarsen would be the first available treatment in the United States for FCS. 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.

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.

“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,” said Brett Monia, CEO of Ionis.

Photo: Brett Monia, CEO of Ionis