Arrowhead Pharmaceuticals has announced positive results from a late-stage study of its investigational RNAi therapeutic in patients with familial chylomicronaemia syndrome (FCS), a rare genetic disorder affecting an estimated one to two per million people.
The phase 3 PALISADE study randomised 75 adults with genetically confirmed or clinically diagnosed FCS to receive one of two dose levels of subcutaneous plozasiran, or matching placebo, once every three months for one year.
There are currently no therapies in the US specifically approved to treat FCS, which prevents the body from breaking down fats consumed through the diet, or triglycerides.
This leads to extremely high triglyceride levels, potentially causing acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis and cognitive issues.
Results presented at this year’s European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine showed that PALISADE met its primary endpoint and all multiplicity-controlled key secondary endpoints.
After ten months of treatment, patients in the 25mg and 50mg plozasiran dose groups demonstrated 80% and 78% median reductions from baseline in triglyceride levels, respectively, compared to 17% for the placebo arm.
Patients receiving plozasiran also achieved an 83% reduction in the risk of developing acute pancreatitis versus placebo. Levels of APOC3, which plays a vital role in slowing the clearance of triglycerides, were also significantly reduced in those receiving Arrowhead’s candidate.
The company’s chief medical scientist, Bruce Given, said: “Based on the data generated to date, we view plozasiran as potentially best-in-class and supportive of development across the spectrum of triglyceride disorders.”
He continued: “The consistency of results in PALISADE suggests that plozasiran response may be independent of the presence of known FCS-associated genetic variants. This is supportive of the potential value of plozasiran in patients with clinically diagnosed disease, regardless of genetic status.”
Plozasiran has already been granted orphan drug and fast track designations by the US Food and Drug Administration (FDA), as well as orphan drug designation by the European Medicines Agency.
Arrowhead said it intends to file a new drug application with the FDA by the end of the year based on results from PALISADE and is planning to seek approval with additional global regulatory authorities.