Transthyretin amyloidosis (ATTR) is a rare, life‐threatening disease resulting from aggregation and deposition of a defective type of protein called (‘amyloids’) in various tissues. These deposits damage the structure and function of the tissues and cause serious disease which is usually fatal if it affects major organs. Transthyretin amyloidosis cardiomyopathy (ATTR‐CM) primarily affects the heart, causing thickening and stiffening of the heart tissues. Symptoms usually start after age 60 years and include shortness of breath, sometimes after only mild exertion; palpitations and abnormal heart rhythms, most frequently atrial fibrillation or atrial flutter; ankle swelling (oedema); fatigue; fainting, and angina (chest pain). ATTR‐CM is progressive and ultimately leads to death. Current treatment focuses mainly on managing the symptoms although heart transplantation may be appropriate for some patients.
Tafamidis is an oral (taken by mouth) drug that has the potential to slow the formation of the amyloid deposits that can produce heart problems in people with ATTR‐CM. Tafamidis works by specifically interfering with the disease process that leads to the formation and deposition of the amyloids within the heart tissues. If approved, tafamidis will become the first medicinal treatment option specifically indicated for treating ATTR‐CM, in patients that currently have very limited options available and that mostly focus on symptom management.
Udenafil works by blocking the enzyme phosphodiesterase type 5 which regulates the breakdown of ‘cyclic guanine monophosphate’ (cGMP) in the blood vessels of the lungs. Increased levels of cGMP leads to dilation (widening) of the vessels improving blood flow to the lungs, reducing the burden on the heart and improving oxygen supply to the blood. This is expected to improve the symptoms of the condition and may offer an additional treatment option for adolescents (12-18 years old) for the management of congenital heart disease after Fontan palliation who currently have few effective therapies available.