Arrowhead adds EU approval for Redemplo in FCS

Arrowhead Pharmaceuticals (Nasdaq: ARWR) has received European Commission marketing authorization for Redemplo (plozasiran) as an adjunct to diet to reduce triglyceride levels in adults with familial chylomicronemia syndrome (FCS). The authorization carries a clinically meaningful distinction: unlike other available options, Redemplo does not require genetic confirmation of FCS for use, potentially broadening access to patients diagnosed on clinical criteria alone.

Redemplo is administered as a subcutaneous injection once every three months. It targets apolipoprotein C-III (APOC3), a liver-produced protein that impairs triglyceride breakdown and clearance. By silencing the APOC3 gene via RNA interference, the drug reduces circulating triglyceride levels through a mechanism distinct from dietary management or fibrate-based approaches. The therapy was developed using Arrowhead’s proprietary Targeted RNAi Molecule (TRiM) platform, which enables tissue-specific gene silencing.

The authorization is supported by data from the Phase III PALISADE study, a randomized, double-blind, placebo-controlled trial enrolling 75 adults with clinically or genetically confirmed FCS. The trial met its primary endpoint and all multiplicity-controlled key secondary endpoints. At the 25 mg dose, plozasiran reduced triglycerides by a median of 80% from baseline versus 17% with placebo. A pooled analysis across both the 25 mg and 50 mg doses demonstrated an 83% reduction in the odds of acute pancreatitis compared with placebo (odds ratio 0.169; p=0.0292). The most commonly reported adverse reactions included hyperglycemia (12.8%), headache (6.8%), nausea (4.7%), and injection site reactions (4.7%).

FCS is a rare, severe disorder in which triglyceride levels typically exceed 10 mmol/L, substantially elevating the risk of recurrent acute pancreatitis, chronic abdominal pain, and related complications. Existing authorized therapies for FCS have generally required genetic confirmation of the condition, limiting their use to a subset of diagnosed patients. The European Medicines Agency noted in its recommendation that Redemplo addresses this gap by providing a treatment option for patients who meet clinical but not necessarily genetic diagnostic criteria.

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Redemplo joins a competitive but limited landscape for FCS. Volanesorsen (Waylivra), an antisense oligonucleotide also targeting APOC3, is authorized in the EU for FCS but requires genetic confirmation and carries a black box warning for thrombocytopenia. Plozasiran’s quarterly subcutaneous dosing and its eligibility criteria that extend to clinically diagnosed patients represent meaningful points of differentiation. The drug has also received approval from the US FDA, Health Canada, China’s National Medical Products Administration, and the Australian Therapeutic Goods Administration, establishing a broad regulatory footprint across major markets.

Arrowhead is additionally investigating plozasiran in severe hypertriglyceridemia through the SHASTA-3 (NCT06347003), SHASTA-4 (NCT06347016), and SHASTA-5 (NCT06880770) Phase III studies, as well as in hypertriglyceridemia via the MUIR-3 (NCT06347133) Phase III study, suggesting the company views the APOC3 axis as a platform opportunity beyond the rare FCS indication.


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