Patisiran

Patisiran is an RNA interference–based therapeutic for hereditary transthyretin-mediated amyloidosis with polyneuropathy. It is marketed under the brand Onpattro and was developed by Alnylam Pharmaceuticals. The drug consists of a small interfering RNA (siRNA) encapsulated in a lipid nanoparticle that targets transthyretin (TTR) mRNA in hepatocytes. By guiding the RNA-induced silencing complex to TTR mRNA, patisiran reduces hepatic production of transthyretin, lowering circulating TTR protein levels by about 80% with ongoing dosing.

Indication and administration: Patisiran is indicated for adults with hereditary transthyretin-mediated amyloidosis with polyneuropathy. It is given as an intravenous infusion at a dose of 0.3 mg/kg once every three weeks, typically over about 60 minutes. Premedication may be used to reduce infusion-related reactions.

Clinical evidence: In the phase III APOLLO trial, patisiran significantly improved neuropathy impairment scores and health-related quality of life compared with placebo, and showed stabilization or improvement in several neuropathic and functional measures.

Regulatory status and safety: Patisiran received FDA approval in 2018 and is approved in the European Union for hereditary transthyretin-mediated amyloidosis with polyneuropathy. Common adverse events include infusion-related reactions, upper respiratory tract infections, nausea, diarrhea, dizziness, headache, flushing, and fatigue. Elevations in liver enzymes have been observed, and hypersensitivity reactions can occur. Patients typically undergo monitoring for infusion reactions and liver function as part of ongoing safety assessments.