APOC2

Arrowhead plans to file for FDA approval of plozasiran by the end of 2024. Arrowhead Pharmaceuticals has shown its hand ahead of a potential showdown with Ionis, publishing phase 3 data on a rare metabolic disease treatment that is racing toward regulators.The biotech shared topline data from the familial chylomicronemia syndrome (FCS) study in June. That release covered the highlights, showing people who took 25 mg and 50 mg of plozasiran for 10 months had 80% and 78% reductions in triglycerides, respectively, compared to 7% for placebo. But the release left out some of the details that could influence how the fight for market share with Ionis shakes out.Arrowhead shared more data at the European Society of Cardiology Congress and in The New England Journal of Medicine. The expanded dataset includes the numbers behind the previously reported hit on a secondary endpoint that looked at the incidence of acute pancreatitis, a potentially fatal complication of FCS.Four percent of patients on plozasiran had acute pancreatitis, compared to 20% of their counterparts on placebo. The difference was statistically significant. Ionis saw 11 episodes of acute pancreatitis in the 23 patients on placebo, compared to one each in two similarly sized treatment cohorts. One key difference between the trials is Ionis limited enrollment to people with genetically confirmed FCS. Arrowhead originally planned to place that restriction in its eligibility criteria but, the NEJM paper says, changed the protocol to include patients with symptomatic, persistent chylomicronemia suggestive of FCS at the request of a regulatory authority.A subgroup analysis found the 30 participants with genetically confirmed FCS and the 20 patients with symptoms suggestive of FCS had similar responses to plozasiran. A figure in the NEJM paper shows the reductions in triglycerides and apolipoprotein C-II were in the same ballpark in each subset of patients.If both biotechs receive labels that reflect their study populations, Arrowhead could potentially target a broader population than Ionis and enable physicians to prescribe its drug without genetic confirmation of the disease. Bruce Given, chief medical scientist at Arrowhead, said on an earnings call in August that he thinks “payers will go along with the package insert” when deciding who can access the treatment.  Arrowhead plans to file for FDA approval by the end of 2024. Ionis is scheduled to learn whether the FDA will approve its rival FCS drug candidate olezarsen by Dec. 19.