Arrowhead Pharmaceuticals has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommending authorization of Redemplo (plozasiran) as an adjunct to diet for reducing triglyceride levels in adult patients with familial chylomicronemia syndrome (FCS). If confirmed by the European Commission, which is expected to issue a decision in Q2 2026, Redemplo would become the first small interfering RNA (siRNA) medicine authorized in the EU for FCS — and notably, the first therapy in that market indicated for both genetically confirmed and clinically diagnosed patients.
The CHMP opinion follows regulatory approvals in the US, Canada, and China, extending what has been a multi-jurisdictional program for Arrowhead’s lead commercial asset. The molecule targets apolipoprotein C-III (apoC-III), a hepatically produced protein that inhibits triglyceride catabolism and clearance. By silencing the mRNA encoding apoC-III using Arrowhead’s proprietary Targeted RNAi Molecule (TRiM) platform, Redemplo aims to restore triglyceride metabolism in a disease where conventional lipid-lowering agents are largely ineffective.
FCS is an ultra-rare disorder, estimated to affect between 1 and 13 people per million globally, and remains widely underdiagnosed. The condition is characterized by triglyceride levels that can reach orders of magnitude above the normal range — typically exceeding 10 mmol/L (880 mg/dL) — driven by loss-of-function mutations affecting lipoprotein lipase activity. The clinical consequences extend beyond lipid abnormalities: patients face a lifelong risk of acute and potentially fatal pancreatitis, alongside chronic abdominal pain, hepatic steatosis, and cognitive impairment. Standard lipid-lowering therapies, including fibrates and omega-3 fatty acids, do not adequately address the LPL-independent pathophysiology of FCS, and dietary fat restriction — often to less than 15 grams per day — remains the primary management strategy despite its limitations.
The CHMP opinion was supported by data from the Phase III PALISADE study (NCT05089084), a randomized, double-blind, placebo-controlled trial enrolling 75 adults with genetically confirmed or clinically diagnosed FCS across 39 sites in 18 countries. The trial’s primary endpoint was percent change from baseline in fasting triglycerides versus placebo at month 10. Patients receiving 25 mg plozasiran once every three months achieved a median 80% reduction in triglycerides from baseline, compared with a 17% reduction in the placebo group. The study also met all multiplicity-controlled key secondary endpoints, including significant reductions in apoC-III levels and a lower incidence of acute pancreatitis in the pooled plozasiran dose groups relative to placebo. Results from PALISADE were published in the New England Journal of Medicine and presented at the European Society of Cardiology Congress 2024 and the American Heart Association Scientific Sessions 2024. A subsequent 2025 analysis published in the Journal of Clinical Lipidology further characterized plozasiran’s effect on acute pancreatitis risk and potential quality-of-life benefit.
The most commonly reported adverse reactions in the trial were hyperglycemia (12.8%), headache (6.8%), nausea (4.7%), and injection site reaction (4.7%). Plozasiran is self-administered via subcutaneous injection once every three months.