FDA Approves First siRNA Therapy Plozasiran for Rare Metabolic Disorder Familial Chylomicronemia Syndrome
Key Insights
The FDA approved Redemplo (search) (plozasiran), the first small interfering RNA therapy for familial chylomicronemia syndrome (search), a rare metabolic disorder with triglyceride levels 10-100 times above normal.
In the phase 3 PALISADE trial, plozasiran achieved an 80% median reduction in triglycerides compared to 17% with placebo at 10 months when administered subcutaneously every 3 months.
The therapy targets apolipoprotein C-III (search) to slow triglyceride breakdown and received Breakthrough Therapy, Fast Track, and Orphan Drug designations from the FDA.
The US Food and Drug Administration approved Redemplo (search) (plozasiran) as the first small interfering RNA therapy for adults with familial chylomicronemia syndrome (search) (FCS (search)), a rare metabolic disorder characterized by triglyceride levels that may reach 10 to 100 times above the normal range. The approval establishes a new treatment option for patients with this condition who face markedly elevated risk for acute pancreatitis (search).
Breakthrough Therapy Targets Rare Metabolic Disorder
FCS (search) is associated with recurrent abdominal pain, diabetes (search), hepatic steatosis (search), cognitive issues, and persistent risk of pancreatitis. The condition affects patients with genetically confirmed or clinically diagnosed familial chylomicronemia syndrome (search), representing a significant unmet medical need in rare disease management.
Redemplo (search) targets apolipoprotein C-III (search), 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, offering a convenient dosing schedule for patients managing this chronic condition.
Phase 3 Trial Demonstrates Significant Efficacy
The FDA approval 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 (search). The study met its primary endpoint, with patients receiving 25 mg of subcutaneous plozasiran every 3 months showing deep and durable triglyceride level reduction.
The median change in fasting triglyceride levels from baseline to 10 months was −80% in the 25-mg plozasiran group, −78% in the 50-mg plozasiran group, and −17% in the placebo group (P < .001). All multiplicity-controlled secondary endpoints were met, including significant reductions in apolipoprotein C-III (search) levels.
Notably, a lower numerical incidence of acute pancreatitis (search) was observed in Redemplo (search)-treated patients compared with placebo, addressing one of the most serious complications associated with FCS (search).
Safety Profile and Market Access
The most common adverse events occurring in at least 10% of treated patients and more than 5% above placebo included hyperglycemia (search), headache, nausea, and injection site reactions. The most common adverse events in the study were abdominal pain, nasopharyngitis, headache, and nausea, with severe or serious adverse events less common among the plozasiran versus placebo population. Some patients with prediabetes or diabetes (search) at baseline experienced hyperglycemia with plozasiran treatment.
No contraindications, warnings, or precautions were identified in the approved prescribing information, supporting the therapy's favorable safety profile in this patient population.
Patient Community Response and Availability
"Today's approval marks a pivotal moment for people living with familial chylomicronemia syndrome (search) and the physicians who support them," said Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation (search). "Because FCS (search) symptoms are mostly invisible, this community historically has been often overlooked and misunderstood, making their journey to effective treatment especially difficult."
Bryan emphasized the collaborative approach in developing this therapy: "We're grateful to Arrowhead for listening to patients and caregivers and incorporating their lived experiences into the development of this transformative therapy. Plozasiran offers real hope for a better future and shows what's possible when innovation is driven by empathy and collaboration addressing patients in need."
Redemplo (search) 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 from the FDA, and global regulatory reviews are ongoing.
This approval represents Arrowhead Pharmaceuticals' first FDA-approved drug and establishes plozasiran as a pioneering treatment option for patients with this rare metabolic disorder.