inotersen

Inotersen is a drug that belongs to the class of antisense oligonucleotides. It is designed to treat hereditary transthyretin-mediated amyloidosis (hATTR) with polyneuropathy by reducing the production of transthyretin (TTR) in the liver. The molecule binds specifically to TTR messenger RNA in hepatocytes, promoting its degradation through RNase H1 and thereby lowering both mutant and wild-type TTR circulating in the blood.

Clinically, inotersen is indicated for adults with hereditary transthyretin-mediated amyloidosis presenting with polyneuropathy. It is administered as a subcutaneous injection once weekly. Because of potential serious adverse effects, its use is accompanied by a risk evaluation and mitigation strategy (REMS) in many jurisdictions, and patients are monitored regularly for safety.

Safety and monitoring considerations are a central part of inotersen therapy. The most important risks are severe thrombocytopenia and glomerulonephritis, which require periodic platelet counts and renal function tests. Additional common or system-specific side effects include injection-site reactions, fatigue, nausea, fever, headache, and anemia. Because lowering TTR can affect retinol transport, monitoring vitamin A levels and supplementation as needed may be advised.

Mechanistically, inotersen reduces hepatic TTR production, leading to lower circulating TTR levels and decreased formation of amyloid deposits in peripheral nerves and other tissues. It is marketed under the brand Tegsedi and was developed by Ionis Pharmaceuticals with its partner Akcea Therapeutics.