QCZ-484: An Investigational RNA Interference Therapeutic for Hypertension

1. Executive Summary

QCZ-484 is an investigational RNA interference (RNAi) therapeutic agent currently under development for the treatment of hypertension. Its mechanism of action involves targeting hepatic angiotensinogen (AGT) synthesis, representing an innovative upstream approach to modulate the renin-angiotensin-aldosterone system (RAAS), a critical pathway in blood pressure regulation.[1] The drug is in the early stages of clinical development, with a Phase 1 study (NCT06905327) initiated to assess its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD).[5] Following this, a Phase 2 dose-finding study (NCT06857955) is planned, which aims to evaluate efficacy and determine an optimal dosing regimen, potentially involving subcutaneous administration every six months.[7]

The development of QCZ-484 was originated by Argo Biopharma, likely under the codename BW-00163.[4] Subsequently, Novartis Pharmaceuticals has taken the lead in its global development through strategic licensing agreements.[11] Should QCZ-484 prove successful in clinical trials, it could offer a significant advancement in hypertension management by providing a long-acting therapeutic option. This approach has the potential to improve patient adherence, a well-recognized challenge in the management of chronic conditions like hypertension, by reducing dosing frequency.