1 Nov 2023 • Patisiran, approved to treat variant ATTR amyloidosis with polyneuropathy, is an RNA interference therapy with a lipid nanoparticle delivery system that targets the common 3′ untranslated region of TTR messenger RNA in the liver to reduce circulating transthyretin protein levels in both variant and wild-type ATTR amyloidosis.

In a phase 3 clinical trial conducted to assess the effectiveness of patisiran, patients with hereditary or wild-type ATTR cardiac amyloidosis were randomly assigned to receive patisiran(181 patients) or a placebo(179 patients) over a 12-month period. The primary endpoint of the study was the change in the distance covered in the 6-minute walk test at 12 months.

Results showed that patients receiving patisiran exhibited a significantly lower decline in the 6-minute walk distance compared to the placebo group, indicating preserved functional capacity. Additionally, the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score improved in the patisiran group while declining in the placebo group. However, no significant benefits were observed in terms of the secondary endpoints, which included a composite of death from any cause and cardiovascular events.

The study findings suggest that patisiran administration over 12 months can result in preserved functional capacity in patients with ATTR cardiac amyloidosis. Notably, infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group.

Source: NEJM | Read full story