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Background: Patients with transthyretin amyloidosis (ATTR) with cardiomyopathy (CM) can experience extracardiac manifestations, including gastrointestinal (GI) manifestations that negatively impact their quality of life.

Methods: In the double-blind HELIOS-B study, patients received vutrisiran 25 mg or placebo every 12 weeks for up to 36 months. Reported adverse events classified using preferred terms of the MedDRA GI disorders system organ class were compared between treatment arms in the overall population, the monotherapy population (not receiving tafamidis at baseline) and the baseline tafamidis subgroup.

Results: Overall, 271/654 patients experienced 529 GI events, 195 in the vutrisiran arm (23.4 events per 100 patient-years) and 334 in the placebo arm (40.6 events/100 patient-years; rate ratio, 0.58; p < 0.0001). With vutrisiran, lower rates were observed for almost all GI events including constipation, diarrhea, nausea, abdominal pain and vomiting, versus placebo, with rates of overall GI events reduced by 38–49% across populations (all p < 0.0001). Reductions in mean cumulative GI events with vutrisiran versus placebo were observed from Month 3.

Conclusions: Treatment with vutrisiran was associated with substantially fewer GI events versus placebo in patients with ATTR-CM, with the difference beginning early in treatment. Future trials should consider assessment of extracardiac manifestations.