Inotersen

Inotersen is an orphan drug from the substance class of RNA interference (RNAi) therapeutics.

Inotersen is an antisense oligonucleotide (ASO) that is used to treat the hereditary form of transthyretin amyloidosis (hATTR).

Antisense oligonucleotides are single-stranded RNA molecules that specifically bind directly to the target RNA and inactivate it. They therefore differ in structure and mechanism of action from the double-stranded siRNA therapeutics (patisiran and vutrisran), which inactivate the mRNA by means of a mechanism naturally present in the cell, but have the same effect of inactivating the defective mRNA and thereby inhibiting the protein biosynthesis of defective TTR and its deposition as amyloid in the tissue of various organs.

Inotersen was first approved in Europe and Canada in 2018, then also in the USA.

Indicated for the treatment of stage 1 or 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR).

Treatment and monitoring should be carried out by a physician experienced in the treatment of amyloidosis.

Comprehensive examination and assessment of liver, kidney, haematology and immune system biomarkers are required prior to treatment, which should also be monitored regularly during treatment in order to detect serious side effects at an early stage!

• Hypersensitivity to the active substance or one of the other ingredients.
• Platelet count < 100 × 10 9 /l before treatment.
• Urinary protein creatinine quotient (UPCR) ≥ 113 mg/mmol (1 g/g) before treatment.
• eGFR < 45 ml/min/1.73^m2.
• Severe liver dysfunction. In case of liver transplantation.
• Pregnancy and lactation (see section Pregnancy and lactation).

Special instructions and precautions:

Patients who discontinue therapy with Inotersen due to platelet counts below 25 × 109/l should not resume therapy.