Abstract
Background and Objective
We assessed the consistency of serum transthyretin (TTR) knockdown with the RNA interference therapeutic vutrisiran across subpopulations of patients with hereditary TTR amyloidosis (ATTR) with polyneuropathy (ATTRv-PN) in HELIOS-A (NCT03759379) and ATTR with cardiomyopathy (ATTR-CM) in HELIOS-B (NCT04153149).
Methods
Patients received vutrisiran 25 mg subcutaneously every 3 months (Q3M). Serum TTR was measured during randomized treatment through Month 18 in HELIOS-A (post-dose/peak and pre-dose/trough sampling) and Month 30 in HELIOS-B (trough only, except Week 6). The effects of intrinsic/extrinsic factors on serum TTR knockdown from baseline were assessed. Pharmacokinetic/pharmacodynamic modeling was used to support consistency in TTR knockdown between studies.