Purpose: Evaluate the impact of patisiran compared to placebo on Norfolk QOL-DN scores in the pre-defined cardiac subpopulation enrolled in the APOLLO trial.
Methods: APOLLO was a Phase 3 multi-center, international, randomized (2:1), double-blind, study of patisiran 0.3mg/kg or placebo IV q3W in patients with hATTR amyloidosis (NCT01960348). Pre-defined cardiac subpopulation included patients with baseline left ventricular (LV) wall thickness = 13mm and no medical history of aortic valve disease or hypertension. Norfolk QOL-DN, a secondary endpoint of the trial, assessed 5 domains: small fiber neuropathy, physical functioning/large fiber; autonomic neuropathy; activities of daily living; and symptoms. Scores for this QOL instrument range from -4 to 136 with a lower score indicating QOL improvement.
Results: APOLLO enrolled 225 patients, the cardiac subpopulation comprised 56% of the total population and had a mean age 61 years (54-67); 78% males; 27% V30M. Mean (95% CI) baseline Norfolk QOL-DN values for patisiran (n=90) and placebo (n=35) in the cardiac subpopulation were 61 (17,102) and 64 (5,119), respectively. In the cardiac subpopulation, patisiran treatment led to significant improvement relative to placebo in Norfolk QOL-DN at 18 months, with a LS mean (95% CI) decrease (improvement) compared to baseline of -3 (-7, 2) points in the patisiran group compared to an LS mean (95% CI) increase (worsening) compared to baseline of 20 (13, 28) points in placebo patients with an overall treatment difference (patisiran –placebo) LS mean (95%CI) -23 (-32, 14). Additionally, patisiran resulted in improvement across all domains relative to placebo. Detailed data will be presented.
Conclusions: These results show that treatment with patisiran improved QOL compared to placebo in hATTR amyloidosis patients with evidence of cardiac involvement. These results are consistent with the outcomes in the overall population, thereby demonstrating that patisiran provides clinical benefit to hATTR amyloidosis patients with both polyneuropathy and cardiomyopathy.