Inotersen therapy of transthyretin amyloid cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Pharmacology

Background:

• Cardiomyopathy is a leading cause of mortality in systemic transthyretin amyloidosis.
• The long-term impact of therapies targeting hepatic production of amyloid precursors on cardiomyopathy remains under investigation.
• Transthyretin amyloid cardiomyopathy (ATTR-CM) requires effective long-term treatment strategies.

Purpose of the Study:

• To assess the long-term safety and efficacy of inotersen, a transthyretin-specific antisense oligonucleotide, in patients with transthyretin amyloid cardiomyopathy.
• To evaluate the impact of inotersen on cardiac structure and function over an extended treatment period.

Main Methods:

• An open-label, single-center study enrolled patients with hereditary or wild-type transthyretin amyloid cardiomyopathy (NYHA class I-III) and left ventricular wall thickness ≥1.3 cm.
• Safety and cardiac structural/functional parameters were prospectively monitored.
• Patients were followed for up to three years.

Main Results:

• Of 33 subjects enrolled, 14 completed three years of treatment.
• At two years, mean left ventricular (LV) mass decreased by 8.4% (MRI), and 6-minute walk test (6MWT) distance increased by 20.2 meters.
• By three years, LV mass further decreased by 11.4%, and 6MWT distance increased by 16.2 meters.

Conclusions:

• Long-term treatment with inotersen is safe and effective for managing amyloid cardiomyopathy.
• Inotersen demonstrates potential in inhibiting the progression of transthyretin amyloidosis and may reverse amyloid burden.
• The study supports inotersen as a viable therapeutic option for transthyretin amyloid cardiomyopathy.