Among 360 patients with the progressive genetic disorder transthyretin amyloidosis (or ATTR amyloidosis), 12 months of treatment with the RNA interference therapeutic agent patisiran “resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis,” APOLLO-B trial investigators write. “Studies of longer duration are needed to determine whether the benefits observed with the reduction of transthyretin mediated by RNA interference are associated with a reduction in mortality and improved hospitalization outcomes in patients with ATTR cardiac amyloidosis.”
The phase 3 trial included patients with hereditary ATTR cardiac amyloidosis. Randomization to patisiran or placebo once every 3 weeks for 12 months had these effects on a primary endpoint of the change from baseline in the distance covered on the 6-minute walk test at 12 months: “At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges–Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group.”
Editorial: “The APOLLO-B trial excluded severely affected patients, who are less likely to have a response to current therapies,” writes an editorialist. “Novel approaches are needed for these patients. It is interesting, therefore, that spontaneous reversal of ATTR cardiomyopathy associated with polyclonal anti-amyloid antibodies has been reported. A phase 1, placebo-controlled trial of the anti-ATTR monoclonal antibody NI006, which is expected to enhance clearance of the deposits, showed a trend toward reducing imaging-based surrogate markers of cardiac amyloid load.”