The US FDA today approved expanded labeling for inclisiran (Leqvio, Novartis) that will permit earlier use of the drug as an adjunct to diet and maximal statin therapy in adults with elevated LDL-C who are at high risk for but have not had a cardiovascular (CV) event, according to Novartis.1
The updated indication for treatment of primary hyperlipidemia expands the population of patients who may benefit from the injectable small interfering RNA (siRNA) therapy, making it available to those requiring primary prevention of cardiovascular disease (CVD) in addition to populations with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). Inclisiran was initially approved in December 2021 for those patient populations.1
After an initial inclisiran injection, a second one is administered 90 days later and then every 6 months thereafter. In the ORION-10 and ORION-11 phase 3 clinical trials,2 inclisiran was associated with LDL-C reductions of up to 52% vs placebo2 in patients with ASCVD or an ASCVD risk equivalent (type 2 diabetes, FH, or 10-year Framingham risk score ≥20%) whose LDL-C remained above target level despite maximum tolerated statin therapy.2
Thirty million Americans are affected by CVD, said Victor Bulto, president, Novartis Innovative Medicines US, in the Novartis statemetn.1 "High LDL-C is one of the most readily modifiable risk factors for heart disease and this label update for Leqvio will help us reach a greater number of patients who struggle with lowering their LDL-C," he stated.1
In other updates to the inclisiran label, the Limitations of Use statement was removed, and the safety section was streamlined to remove 4 adverse events since the frequency of these events in inclisiran-treated participants was the same as in participants in the placebo arm.1
Data collection continues across the Novartis VictORION cardiovascular clinical trial program, comprised of 27 trials with enrollment of more than 60 000 participants across 50 countries. Inclisiran is being studied in high-risk primary prevention and secondary prevention.
1. US FDA approves expanded indication for Novartis Leqvio® (inclisiran) to include treatment of adults with high LDL-C and who are at increased risk of heart disease. News release. Novartis Pharmaceuticals Corporation. July 10, 2023. Accessed July 10, 2023.
2. Ray KK, Wright RS, Kellend D, et al. Two phase 3 trials of inclisiran in patients with elevated LCL cholesterol. N Engl J Med. 2020; 382:1507-1519. doi:10.1056/NEJMoa1912387