Huddersfield Royal Infirmary

Ionis Pharmaceuticals is looking to extend the reach of Tryngolza (olezarsen) beyond its initial approval for an ultra-rare genetic lipid disorder, as new Phase III trial data suggest its drug could become the first treatment option for a much larger patient group. On Tuesday, the company reported that an 80-mg monthly dose of the RNA-targeted medicine lowered fasting triglyceride levels by 72% in the CORE study and 55% in the CORE2 study, compared to placebo, in patients with severe hypertriglyceridaemia (sHTG). A 50-mg dose produced placebo-adjusted reductions of 63% and 49%, respectively. Both studies, which together enrolled a total of 1063 participants, required patients to remain on standard lipid-lowering therapy throughout the trial period.The trials also met their secondary endpoint, showing a substantial decline in acute pancreatitis events. Across both trials, pooled data indicated that Tryngolza reduced such events by 85% versus placebo over 12 months, the first therapy to do so, according to Sam Tsimikas, Ionis' head of global cardiovascular development"Despite current standard of care and lifestyle changes, people with sHTG — who could have triglyceride levels reaching into the thousands — remain vulnerable to unpredictable and life-threatening acute pancreatitis attacks," Tsimikas said. Participants were randomised to receive Tryngolza or placebo every four weeks via subcutaneous injection for a year. Adverse events were generally mild, with injection site reactions being the most common side effect. Year-end filing Ionis intends to file a supplemental new drug application with the FDA by year-end, with detailed trial data slated for presentation at an upcoming medical conference. The readout could position Ionis to expand beyond the narrow market it entered last December, when the FDA approved Tryngolza for familial chylomicronaemia syndrome (FCS), a rare subtype of sHTG. While FCS represents only about 3000 US patients, sHTG affects some 3 million people in the country, including more than a million who are considered high risk. In an interview with FirstWord last year, CEO Brett Monia said that "having first-mover advantage just solidifies our leadership in this space," as the company looks to tackle other forms of sHTG. For more, see – ViewPoints: Though Tryngolza faces modest FCS market, nod offers foot in door to larger opportunity.