- Transthyretin amyloidosis (ATTR) is a severe, progressive, systemic disease characterized by cardiomyopathy (ATTR-CM) and/or neuropathy (ATTR-PN) and associated with high mortality
- ATTR is caused by misfolding of the TTR protein, either due to (i) an inherited genetic variant of the TTR gene (ATTRv) or (ii) a spontaneous anomaly, known as wild-type ATTR (ATTRwt) [1]
- In ATTR amyloidosis, naturally occurring TTR homotetramers dissociate into unstable monomers that misfold and aggregate into insoluble TTR amyloid fibrils [2]; depending on ATTR type, the amyloid is deposited into various organs and/or nerves, which can lead to permanent damage and organ malfunction
- Risk Factors and Demographics
- The cause for the instability of the wild-type TTR homotetramer remains unknown, but age-associated factors are implicated [4]
- Although there are a few cases of people being diagnosed as early as their late 40s; the average age at diagnosis is >75 years [7]
- ATTRwt is more common in males (>85% over age 60); no racial predilection reported [5]
- ATTRwt may be present in up to 25% of men over age 80; clinically significant disease can occur among 8%-16% of people in this age group [8]
- The cause for the instability of the wild-type TTR homotetramer remains unknown, but age-associated factors are implicated [4]
- Epidemiology
- The true prevalence and incidence of ATTRwt amyloidosis are not known [9-10]
- Recent literature aligns on the hypothesis that the diagnosed prevalence of ATTR-CM will increase due to improvements in non-invasive diagnostics and targeted therapies to treat patients with ATTR-CM
- ALEXION’s upper bounds estimate is ~1.8 million individuals in the 7 Major Markets* + China, with most patients undiagnosed [9]
- In Japan, ALEXION estimates the prevalence of ATTRwt is ~68K [9]
- Compare: ATTRv amyloidosis prevalence in Japan is estimated to be ~1,600 [9]
- Prognosis
- High mortality: median OS for all patients is ~3.6 years [6,7]
- Debilitating physical symptoms similar to those of heart failure, including exercise intolerance and fatigue [3]
- Decreased functional capacity and reduced quality of life (QoL) [3]
* 7 Major Markets = US, EU5 (France, Germany, Italy, Spain, UK), Japan