A new study has demonstrated that 12 months of patisiran treatment was effective in improving or stabilizing polyneuropathy disability (PND) scores, quality of life (QoL), and autonomic functions in patients with hereditary transthyretin-mediated amyloidosis (hATTR).

The study, published in Neurology, found that patients with hATTR benefited from the therapy regardless of their genotype or phenotype.

Patisiran is an RNAi therapeutic approved by the US Food and Drug Administration (FDA) for the treatment of hATTR. It is a gene silencer that employs lipid nanoparticles to deliver RNA to impede the production of abnormal transthyretin by targeting and reducing production of TTR in the liver.

hATTR is a rare, progressive condition characterized by the accumulation of abnormally folded amyloid in organs and organ systems, particularly in the heart, eyes, gastrointestinal tract, kidneys, and peripheral nervous system. Occasionally, amyloidosis also occurs in the autonomic and central nervous systems.

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The study was a multicenter, observational, phase 4 study carried out with 58 patients with hATTR and the V122I or T60A variants in the United States. These variants are associated with cardiomyopathy and, sometimes, a mixed cardiac and neurologic phenotype. The primary endpoint was improvement or stabilization of PND scores versus baseline after 12 months of therapy with patisiran. Additional endpoints included neuropathy and cardiomyopathy-related QoL, autonomic symptoms, and severity of cardiac dysfunction.

Nearly 90% of the included patients had a mixed phenotype. Some 10.3 had neuropathy without heart failure, and 89.7% had heart failure.

Forty-five patients completed the study, and at 12 months, 42 demonstrated improved or stabilized PND scores. Patients also showed improved QoL and dysautonomia. Patisiran was found to have an acceptable safety profile. The authors conclude that patisiran may be effective in improving or stabilizing PND scores and improving QoL and autonomic function after 12 months of therapy.


Comenzo RL, Shu F, Malhotra S, et al. Effect of patisiran on polyneuropathy and cardiomyopathy in patients with hATTR amyloidosis with V122I/T60A variants: a phase 4 observational study (S14.005). Neurology. Published online April 25, 2023;17(suppl 2):2959. doi:https://doi.org/10.1212/WNL.0000000000202917