Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis

This phase 3 randomized trial (APOLLO-B) assessed patisiran—a lipid nanoparticle siRNA therapeutic—in 360 patients with hereditary or wild-type transthyretin cardiac amyloidosis. Administered every 3 weeks for 12 months, patisiran preserved functional capacity and quality of life. The 6-minute walk test declined less in the patisiran group (–8.15 m) vs. placebo (–21.35 m), with a statistically significant median difference (14.69 m; P=0.02). KCCQ-OS scores improved in patisiran patients (+0.3 points) but declined with placebo (–3.4 points; difference 3.7; P=0.04). NT-proBNP and troponin I levels increased less in the patisiran group. LV mass and strain measures favored patisiran. Serum transthyretin was reduced ~87%. Adverse events were mild/moderate; infusion reactions, arthralgia, and muscle spasms were more common with patisiran. No significant reduction was seen in composite endpoints for mortality/hospitalizations, though trends favored patisiran. The study supports siRNA-mediated transthyretin suppression as a stabilizing therapy in ATTR cardiomyopathy.

This phase 3 randomized trial (APOLLO-B) assessed patisiran—a lipid nanoparticle siRNA therapeutic—in 360 patients with hereditary or wild-type transthyretin cardiac amyloidosis. Administered every 3 weeks for 12 months, patisiran preserved functional capacity and quality of life. The 6-minute walk test declined less in the patisiran group (–8.15 m) vs. placebo (–21.35 m), with a statistically significant median difference (14.69 m; P=0.02). KCCQ-OS scores improved in patisiran patients (+0.3 points) but declined with placebo (–3.4 points; difference 3.7; P=0.04). NT-proBNP and troponin I levels increased less in the patisiran group. LV mass and strain measures favored patisiran. Serum transthyretin was reduced ~87%. Adverse events were mild/moderate; infusion reactions, arthralgia, and muscle spasms were more common with patisiran. No significant reduction was seen in composite endpoints for mortality/hospitalizations, though trends favored patisiran. The study supports siRNA-mediated transthyretin suppression as a stabilizing therapy in ATTR cardiomyopathy.