The US Food and Drug Administration approved Redemplo (plozasiran) as an adjunct to dietary management to reduce triglyceride concentrations in adults with familial chylomicronemia syndrome, a rare metabolic disorder characterized by triglyceride levels that may reach 10 to 100 times above the normal range and confer a markedly elevated risk for acute pancreatitis. This approval establishes Redemplo as the first small interfering RNA therapy evaluated in patients with genetically confirmed or clinically diagnosed familial chylomicronemia syndrome (FCS).

FCS is associated with recurrent abdominal pain, diabetes, hepatic steatosis, cognitive issues, and persistent risk of pancreatitis. Redemplo targets apolipoprotein C-III, a hepatic protein that elevates triglyceride levels by slowing the breakdown and clearance of triglyceride-rich lipoproteins. The therapy is administered subcutaneously once every 3 months using Arrowhead’s Targeted RNAi Molecule platform.

The US Food and Drug Administration decision was supported by data from the phase 3 PALISADE trial, a randomized, double-blind, placebo-controlled study in adults with genetically confirmed or clinically diagnosed FCS. Redemplo met the primary endpoint, achieving a median triglyceride reduction of approximately 80% from baseline compared with 17% in the pooled placebo group at month 10. All multiplicity-controlled secondary endpoints were met, including significant reductions in apolipoprotein C-III. A lower numerical incidence of acute pancreatitis was observed in Redemplo-treated patients compared with placebo. The most common adverse events, occurring in at least 10% of treated patients and more than 5% above placebo, included hyperglycemia, headache, nausea, and injection site reactions. No contraindications, warnings, or precautions were identified in the approved prescribing information.

Redemplo is expected to be available in the US before the end of the year. Arrowhead will offer a support program, Rely On REDEMPLO, to assist patients throughout treatment. The therapy received Breakthrough Therapy, Fast Track, and Orphan Drug designations, and global regulatory reviews are ongoing.

Source: Arrowhead Pharmaceuticals