Ionis’ olezarsen slashes triglycerides and pancreatitis in rare disease patients

Ionis’ olezarsen slashes triglycerides and pancreatitis in rare disease patients

Ionis Pharmaceuticals has achieved a significant milestone in its phase 3 clinical trial for lipid-lowering therapy, bringing the company closer to seeking independent commercial approval. The trial focused on assessing the effects of Ionis’ ligand-conjugated antisense medicine, olezarsen, in patients with familial chylomicronemia syndrome (FCS), a rare condition. Notably, this marks Ionis’ first potential independent commercial launch, following a previous FDA rejection of its treatment volanesorsen in 2019 for the same condition.

The pivotal data emanate from a phase 3 trial that included 66 adult participants, randomized to receive either a placebo or one of two monthly subcutaneous doses of olezarsen. Over a span of six months, Ionis observed a statistically significant reduction in triglyceride levels among patients receiving the higher 80-mg dose. This outcome enabled the trial to meet its primary endpoint, substantiated by a highly significant p-value of 0.0009. In contrast, the lower 50-mg dose showed no statistical advantage over the placebo in reducing triglycerides.

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“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. 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.” 

– Brett P. Monia, Ph.D., chief executive officer of Ionis

Notably, Ionis reported that no patient administered the 80-mg dose experienced an acute pancreatitis event during the trial, a stark contrast to the 11 such events observed in the placebo group. Moreover, the 50-mg dose was associated with a noteworthy reduction in pancreatitis risk.

“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. 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.”

– Sam Tsimikas, M.D., senior vice president, global cardiovascular development at Ionis

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In addition to its success in triglyceride reduction, the 80-mg dose of olezarsen achieved a reduction of over 75% in apoC-III, the target protein. Ionis also highlighted the favorable safety and tolerability profile of this dose, although specific safety data have not been disclosed. The company did mention that most adverse events in patients receiving olezarsen were mild, with no reported hepatic or renal toxicity events and no clinically significant platelet reductions. Importantly, one patient’s death was deemed unrelated to the drug.

With these promising results, Ionis is now poised to seek FDA approval in early 2023, marking a significant step toward offering the first-ever treatment for FCS in the United States. Additionally, Ionis is conducting phase 3 trials in severe hypertriglyceridemia, a much larger patient population, fueling the biotech’s optimism that olezarsen could potentially yield blockbuster sales in the future.

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