Novartis' Leqvio significantly reduces LDL-C in late-stage ASCVD trial

Novartis announced that its biannual injectable small interfering RNA (siRNA) therapy, Leqvio (inclisiran), achieved the primary objectives in a Phase III clinical trial. The study focused on patients with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk who are not currently on lipid-lowering therapies. Novartis’ chief medical officer, Shreeram Aradhye, emphasized the importance of cholesterol reduction, calling it one of the "world’s biggest healthcare challenges." He noted that this trial contributes significantly to the growing evidence supporting Leqvio across the entire spectrum of ASCVD.

The V-MONO trial, which included 350 participants at low to moderate risk of developing ASCVD, demonstrated that Leqvio resulted in a clinically meaningful and statistically significant reduction in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 150. These results were compared against both a placebo and ezetimibe. Novartis plans to present detailed findings at an upcoming medical conference and will discuss them with the FDA and other regulatory agencies.

The V-MONO study is part of Novartis' comprehensive VictORION program, which explores Leqvio's efficacy in both primary and secondary prevention of cardiovascular diseases. This extensive clinical program also encompasses the VICTORION-1-PREVENT (V1P) trial, noted as the only non-statin lipid-lowering therapy study aimed at high-risk primary prevention. Additional secondary prevention studies, ORION-4 and VICTORION-2-PREVENT (V2P), are scheduled to report their results in 2026 and 2027, respectively.

Leqvio was initially discovered by Alnylam Pharmaceuticals and further developed through a partnership with The Medicines Company. Novartis acquired The Medicines Company in 2020 for $9.7 billion, thereby securing global rights to Leqvio under a license and collaboration agreement with Alnylam. The siRNA therapy targets the PCSK9 pathway and received its first approval in Europe in 2020 for hypercholesterolemia or mixed dyslipidemia in adults. In the United States, the drug's approval process faced initial hurdles due to manufacturing site deficiencies, but it was ultimately approved on the second attempt for reducing LDL-C in patients on maximally tolerated statin therapy.

A recent survey conducted by FirstWord among US cardiologists showed a growing adoption of Leqvio, with 44% of respondents currently prescribing the medication. Leqvio faces competition from other injectable PCSK9 inhibitors such as Regeneron Pharmaceuticals' Praluent (alirocumab) and Amgen's Repatha (evolocumab). In the realm of investigational oral PCSK9 inhibitors, Merck & Co. commenced late-stage testing of MK-0616 last year, while AstraZeneca recently presented early Phase I data for its candidate AZD0780.