hATTR is a rare, multisystem, rapidly progressive, life-threatening disease caused by a mutation in the gene.

Objectifs : Patisiran, an investigational RNAi therapeutic, reducesproduction of mutant and wild-type TTR. This report describes the efficacy and safety of patisiran from phase 3 Apollo study.

Multi-center, international, randomized (2 :1), DBPC study of patisiran 0,3mg or placebo IV q3W in patients with hATTR. Primary endpoint : change from baseline at 18 months in composite mNIS+7 neuropathy impairment score. Secondary endpoints : QOL, motor strength, disability, gait speed, nutritional status and autonomic function. 225 patients enrolled (19 countries) mean age 61 years, 39 different TTR mutations, mean NIS 59,3 (6,0,141,6), 75 % PND>1 (walking difficulties) and 56 % with cardiac involvement.

At 18 months, mean change from baseline in mNIS+7 demonstrated significant improvement with patisiran compared to placebo (p=9,26,10–24). All secondary endpoints demonstrated statistically significant favorable differences in the patisiran arm compared to placebo (p<0,001).

Similar frequency of AEs (96,6 %, 97,4 %), SAEs (36,5 %, 40,3 %), and deaths (4,7 %, 7,8 %) in the patisiran and placebo groups, respectively. AEs reported in ≥10 % and more frequently with patisiran were peripheral edema and IRRs, both generally mild or moderate. Apollo is the largest, controlled study in hATTR amyloidosis and included a wide range of TTR genotypes and neuropathy severity and majority with cardiac involvement.

Use of patisiran resulted in significant improvement in motor, sensory and autonomic neuropathy, a significant reduction in disease symptoms, and favorable safety profile compared placebo.