Disease Overview

  • 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
ATTRwt:
  • 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]
  • 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​
  1. ALXN: ATTR Amyloidosis: Epidemiology Dossier. August 20, 2021. Citing Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86(9):1036-43. and Hawkins PN, Ando Y, Dispenzeri A, Gonzalez-Duarte A, Adams D, Suhr OB. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47(8):625-38.
  2. ALXN: Acoramidis ​for the Treatment of ATTR-CM: Training Deck. November 22, 2021. 34_Acoradmidis Training Deck_22Nov21 FINAL.
  3. Maurer MS, et al. Circ Heart Fail. 2019;12:e006075.
  4. Ruberg FL, et al. J Am Coll Cardiol. 2019;73:2872-2891.
  5. ALXN: 03_Acoramidis Sci Plat in Symphony_v1(06Aug21)_s2c. Citing: Cuddy SAM, Faulk RH. Can J Cardiol. 2020;36:396-407; Yamamato H, Yokochi T. ESC Heart Fail. 2019;6:1128-1139; & Kroi F, et al. Cardiol Ther. 2020; https://doi.org/10.1007/s40119-020-00205-3.
  6. Garcia-Pavia, P., Bengel, F., Brito, D., Damy, T., Duca, F., Dorbala, S., Nativi-Nicolau, J., Obici, L., Rapezzi, C., Sekijima, Y. and Elliott, P.M. (2021), Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy. Eur J Heart Fail, 23: 895-905. https://doi.org/10.1002/ejhf.2198.
  7. ALXN: 03_Acoramidis Sci Plat in Symphony_v1(06Aug21)_s2c. Citing: Liu PP, Smyth D. Circulation. 2016;133:245-247; Muchtar E, et al. J Intern Med. 2021;289:268-292 & Ruberg FL, Berk JL. Circulation. 2012;126:1286-1300. NOTE: 3.5 years per UptoDate. https://www.uptodate.com/contents/amyloid-cardiomyopathy-treatment-and-prognosis?search=attr&source=search_result&selectedTitle=3~27&usage_type=default&display_rank=3.
  8. ALXN: 03_Acoramidis Sci Plat in Symphony_v1(06Aug21)_s2c. Citing: Cuddy SAM, Faulk RH. Can J Cardiol. 2020;36:396-407 & Cornwell GG, et al. Am J Med. 1983;75:618-623.
  9. ALXN: ATTR Amyloidosis: Epidemiology Dossier. Elissa Wilker & Shona Fang. September 2021.
  10. ALXN: Acoramidis ​for the Treatment of ATTR-CM: Training Deck. November 22, 2021. 34_Acoradmidis Training Deck_22Nov21 FINAL. Citing: Maurer MS, et al. Circ Heart Fail. 2019;12:e006075 & Cuddy SAM, Faulk RH. Can J Cardiol. 2020;36:396-407.