Novartis new analysis further shows durable and potent LDL-C reduction with inclisiran, an investigational first-in-class siRNA cholesterol-lowering treatment

• Prespecified analysis of pooled data from ORION-9, -10 and -11 Phase III clinical trials shows inclisiran reduced low-density lipoprotein-cholesterol (LDL-C) by 51% at 17 months¹
   
• Prespecified exploratory analysis based on safety reporting from the three trials, showed fewer major adverse cardiovascular events (MACE) with inclisiran compared to placebo¹
   
• The data are consistent with LDL-C lowering as a strong surrogate for improved patient cardiovascular outcomes² and reaffirms rationale for the ongoing ORION-4 trial

Basel, March 28, 2020 — Novartis today announced results from a prespecified analysis of pooled data from three Phase III studies evaluating the safety and efficacy of inclisiran, its first-in-class investigational treatment for hyperlipidemia in adults. The data was presented during a Late Breaker session at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC Virtual). The pooled analysis of the ORION-9, -10 and -11 Phase III trials showed a durable and potent reduction in LDL-C of 51% when used in addition to other lipid-lowering therapies (LLT) over 17 months of treatment¹. The prespecified analysis of pooled data is consistent with the efficacy and safety findings of the individual Phase III trial results recently published in The New England Journal of Medicine.

Additionally, a prespecified exploratory analysis using the safety reporting from all three trials indicated fewer MACE with inclisiran compared to placebo (7.1%, 9.4% respectively)¹. The overall safety and tolerability profile was generally similar between the inclisiran and placebo groups. While these preliminary observations are based on a low number of events, they are consistent with the general concept that however LDL-C is lowered, it is thought to result in reduced risk of future cardiovascular events². This further supports the research currently underway in the Phase III ORION-4 trial. The ORION-4 trial aims to recruit 15,000 participants – from 150 sites in the United States and the United Kingdom – with pre-existing atherosclerotic cardiovascular disease (ASCVD) and who are unable to achieve LDL-C goal. Expected to finish in 2024, this trial will bring additional information on inclisiran’s effects on cardiovascular outcomes.