Combinations of antisense agents, pharmaceutical compositions and methods of use

A combination of dsRNAi agents targeting PCSK9 and HMGCR addresses the need for potent and convenient LDL-C lowering treatments, effectively reducing LDL-C levels and mitigating cardiovascular risks.

WO2026133250A1 Publication Date: 2026-06-25NOVARTIS AG
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Patent Information

Application Number
PCT/IB2025/063176
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-12-20
Filing Date
2025-12-18
Publication Date
2026-06-25

AI Technical Summary

Technical Problem

There is an unmet need for LDL-C lowering treatments with increased potency and durability of action, as well as more convenient treatments for subjects with lipid metabolism disorders, particularly due to the adverse side effects of current therapies like statins and poor patient adherence.

Method used

A combination of first and second antisense agents, such as double stranded RNAi (dsRNAi) agents, are used to inhibit PCSK9 and HMGCR expression, which can be administered separately or concurrently, to lower LDL-C levels and treat atherosclerotic cardiovascular disease.

Benefits of technology

The combination effectively inhibits PCSK9 and HMGCR expression, leading to reduced LDL-C levels and a decreased risk of cardiovascular events, providing a more potent and convenient treatment option compared to existing therapies.

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Abstract

Disclosed are, inter alia, combinations comprising a first antisense (e.g., first double stranded RNAi (dsRNAi)) agent for inhibiting expression of proprotein convertase subtilisin kexin 9 (PCSK9), for example, human PCSK9, and a second antisense agent (e.g., second dsRNAi agent) for inhibiting expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR); pharmaceutical compositions including the same, and methods of treatment using the same.
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