Novartis Completes $9.4B Acquisition of The Medicines Company, Gaining Groundbreaking PCSK9-Targeting RNAi Drug Inclisiran with Twice-Yearly Dosing

January 09, 2020 /BioValleyBIOON/ -- Swiss pharmaceutical giantNovartis(Novartis) recently announced the completion of its acquisition of The Medicines Company (TMC). The acquisition, first announced in November 2019, centers on the core asset inclisiran, an RNAi therapeutic for lowering cholesterol.

Novartis CEO Vas Narasimhan stated, “The acquisition of this pharmaceutical company and the cholesterol-lowering drug inclisiran has enabledNovartis“We have a unique opportunity to pioneer a new chapter in the treatment of the world’s leading causes of death and disability, using vaccine-like approaches. This is an important step in our journey to focus on our company, reimagine medicine, and transform patients’ lives.”

Novartis CEO Marie France Tschudin stated, “I look forward to welcoming colleagues from The Medicines Company (TMC) toNovartisThere is a genuine unmet medical need among patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) who, despite receiving standard-of-care treatment, have not achieved their low-density lipoprotein cholesterol (LDL-C) treatment goals and remain at significant risk for cardiovascular events. Inclisiran, with its unique twice-yearly subcutaneous dosing regimen that seamlessly integrates with routine healthcare provider (HCP) visits, has the potential to improve adherence and, consequently, clinical outcomes in patients with ASCVD or FH.”

In December 2019, TMC had submitted to the U.S. Food and Drug Administration (FDA) submitted a New Drug Application (NDA) for inclisiran for secondary prevention in patients with ASCVD or FH.

Inclisiran is a small interfering RNA (siRNAor sir-nah) class of cholesterol-lowering therapies, targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a key mechanism by which the human body regulates LDL-C. The PCSK9 protein reduces the liver’s ability to clear low-density lipoprotein cholesterol (LDL-C) from the bloodstream, and LDL-C is widely recognized as a major risk factor for cardiovascular disease (CVD). Targeting PCSK9 offers an entirely new therapeutic modality for combating LDL-C and is regarded as the most significant advancement in lipid-lowering therapy since the introduction of statins (such as Lipitor).

To date, two monoclonal antibody drugs targeting PCSK9 protein inhibition have been approved for market launch: Amgen’s Repatha and Sanofi/Regeneron’s Praluent. Unlike monoclonal antibody PCSK9 inhibitors, inclisiran, as an RNAi therapeutic, works by directly silencing the production of PCSK9 protein in the liver. Inclisiran is a small interfering RNA (siRNA) that leverages the body’s natural RNA interference mechanism. It binds to the mRNA encoding the PCSK9 protein, reducing mRNA levels through RNA interference and thereby preventing hepatic production of PCSK9. This enhances the liver’s ability to clear LDL-C from the bloodstream, resulting in lowered LDL-C levels.

Currently, inclisiran is in Phase III clinical development to evaluate its ability to lower LDL-C with twice-yearly dosing. Inclisiran was developed by Alnylam Pharmaceuticals using its proprietary Enhanced Stability Chemistry (ESC)-GalNAc conjugation technology, which enables GalNAc chemical modification of RNA fragments to enhance stability and facilitate liver-targeted drug delivery. The Medicines Company has entered into a license and collaboration agreement with Alnylam, securing global rights for the development, manufacturing, and commercialization of inclisiran.

Despite lagging behind other PCSK9 inhibitors, the treatment convenience of inclisiran, which requires only two subcutaneous injections per year during the maintenance phase, provides it with significant market penetration opportunities in the cholesterol-lowering drug market. Credit Suisse previously predicted that the global annual sales of inclisiran would reach $1.13 billion in 2024. (Bioon.com)

Original source:Novartis successfully completes acquisition of The Medicines Company, adding a potentially first-in-class, investigational cholesterol-lowering therapy inclisiran