TABLE 2.

Main studies evaluating treatment for transthyretin (TTR) CA with functional end-points.

	ATTR silencers		ATTR stabilizers
Molecule	Patisiran siRNA LNP	Inotersen 2′- MOE modified ASO	Tafamadis
Study	APOLLO 2018 randomized controlled trial (47) 225 patients ATTRv polyneuropathy	NEURO-TTR 2018 randomized controlled trial (48) 172 ATTRv polyneuropathy patients, 105 (61%) with cardiac involvement	ATTR-ACT study (44) 441 ATTR-CA patients (106 ATTRv-CA and 335 ATTRwt-CA)
Main results	Patisiran significantly improved neuropathy scores, QOL, walking parameters, nutritional status, and activities of daily living	Inotersen modified the course of neuropathy and improved QOL	Tafamidis was associated with a reduction in all-cause mortality and cardiovascular hospitalizations
Functional evaluation	In a pre-specified ATTRv-CA subgroup, Patisiran improved functional capacity (10-m walk test)	In an interim analysis, 33 patients with ATTR-CA treated with inotersen had decreased LV mass and improved exercise tolerance in 6MWT (46)	Secondary end points were notable for a lower rate of functional capacity decline (6MWT distance) and of quality-of-life decline
Future studies with functional end-points	APOLLO B https://ClinicalTrials.gov/show/NCT03997383 Evaluate Patisiran for ATTRv-CA and ATTRwt-CA with the primary end point of 6-minute walk test (6MWT) performance and secondary end points of death and hospitalization at 12 months.

2′- MOE, 2′- O- methoxyethyl; ASO, antisense oligonucleotide; ATTR, amyloid transthyretin; ATTRwt, wild type transthyretin amyloidosis; ATTRv, hereditary transthyretin amyloidosis; LV mass, Left Ventricular mass; ATTR-ACT, Safety and efficacy of tafamidis in patients with transthyretin cardiomyopathy; ATTR-CA, transthyretin amyloidosis with cardiomyopathy; QOL, quality of life; 6MWT, 6-min walk test.