Regardless of body mass index (BMI), Leqvio provided sustained and effective LDL-C reduction of ~50% with two doses a year**, according to pooled analysis of three Phase III studies 1

Being overweight or obese is often associated with elevated LDL-C levels, or “bad” cholesterol, and may contribute to an increased risk for a cardiovascular event, such as a heart attack or stroke2

LDL-C is one of the most readily modifiable risk factors for ASCVD; however, despite widespread statin use, up to 80% of patients do not reach guideline-recommended LDL-C targets3,4
Basel, November 8, 2021 — Novartis today announced results from a pooled post-hoc analysis of Phase III ORION-9, -10 and -11 trials, exploring the impact of body mass index (BMI) levels on the efficacy and safety of twice-yearly** Leqvio® (inclisiran). At month 17, Leqvio was well-tolerated and provided effective and sustained reduction of approximately 50%, difference from placebo, in low-density lipoprotein cholesterol (LDL-C) when used in addition to other lipid-lowering therapies across all BMI types1. Results were presented at the American Heart Association Scientific Sessions 2021.

“For patients with vascular disease who have a high BMI, physicians generally recommend weight loss in addition to cholesterol-lowering medication," said Lawrence A. Leiter, MD, Director of the Lipid Clinic, Associate Director of the Clinical Nutrition and Risk Factor Modification Centre and Associate Scientist in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Canada. “Despite our best efforts, however, weight loss isn’t always achievable. The BMI analysis sheds new light on the potential of inclisiran (Leqvio) in helping patients reduce their LDL-C by up to half with only twice-yearly dosing no matter what their weight.”

Regardless of BMI, Leqvio showed effective and sustained lipid lowering compared to placebo across a range of atherogenic lipids demonstrating that its pharmacology does not appear to be impacted by excessive body weight. In addition to lowering LDL-C levels by approximately 50%, reductions were also seen across triglycerides (~10%), total cholesterol (~33%), non-HDL-C (~45%) and ApolipoproteinB (~40%). The trials included adults with ASCVD, HeFH and ASCVD risk equivalent1. Leqvio had a tolerability profile similar to placebo. Serious adverse events increased with BMI levels in both placebo and Leqvio treatment arms. Treatment emergent adverse events (TEAEs) at the injection site were more frequent with Leqvio, but all were mild or moderate1. The effect of Leqvio on cardiovascular morbidity and mortality has not been determined.

*Product and brand name are currently under FDA review.
**After an initial dose and one at three months.

About the ORION Phase III low-density lipoprotein cholesterol (LDL-C)-lowering studies
ORION-9 was a pivotal Phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Leqvio 300 mg, equivalent to 284 mg of Leqvio, administered subcutaneously by a healthcare professional. Starting with an initial dose5, Leqvio was then administered again at three months and then every six months thereafter in 482 participants with clinical or genetic evidence of heterozygous familial hypercholesterolemia and elevated LDL-C, despite a maximally tolerated dose of LDL-C-lowering therapies (e.g., a statin or ezetimibe). For the primary endpoints of ORION-9, Leqvio delivered mean placebo-adjusted percentage change in LDL-C reductions of 48% (P<.0001) at 510 days and demonstrated time-adjusted percentage change in LDL-C reductions of 44% (P<.0001) from 90 through 540 days. The international study was conducted at 46 sites in eight countries5,6.

ORION-10 was a pivotal Phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Leqvio 300 mg, equivalent to 284 mg of Leqvio, administered subcutaneously by a healthcare professional. Starting with an initial dose7, Leqvio was then administered again at three months and then every six months thereafter in 1,561 participants with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C, despite a maximally tolerated dose of LDL-C-lowering therapies (e.g., a statin and/or ezetimibe). For the primary endpoints of ORION-10, Leqvio delivered mean placebo-adjusted percentage change in LDL-C reductions of 52% (P<.0001) at 510 days and demonstrated time-adjusted percentage change in LDL-C reductions of 54% (P<.0001) from 90 through 540 days. The study was conducted at 145 sites in the United States6,7.

ORION-11 was a pivotal Phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Leqvio 300 mg, equivalent to 284 mg of Leqvio, administered subcutaneously by a healthcare professional. Starting with an initial dose7, Leqvio was then administered again at three months and then every six months thereafter in 1,617 patients with ASCVD or ASCVD-risk equivalents and elevated LDL-C despite a maximally tolerated dose of statin therapy (with or without ezetimibe). For the primary endpoints of ORION-11, Leqvio delivered placebo-adjusted change in LDL-C reductions of 50% (P<.0001) at 510 days and demonstrated time-adjusted LDL-C reductions of 49% (P<.0001) from 90 through 540 days. The international study was conducted at 70 sites in seven countries6,7.

The Phase III ORION-9, -10 and -11 trials are part of the larger Leqvio VictORION dynamic evidence generation program.

About atherosclerotic cardiovascular disease (ASCVD)
Atherosclerosis corresponds to the accumulation of lipids over time mainly low-density lipoprotein cholesterol (LDL-C) in the inner lining of the arteries. Unexpected rupture of the atherosclerotic plaque can cause an atherosclerotic cardiovascular event such as a heart attack or stroke8,9. ASCVD accounts for over 85% of all cardiovascular disease deaths10. ASCVD is the primary cause of death in the European Union and its burden in the United States is greater than that from any other chronic diseases11,12. ASCVD risk-equivalent corresponds to conditions that confer a similar risk for an ASCVD event (e.g., diabetes, heterozygous familial hypercholesterolemia)7,13.

About Leqvio® (inclisiran)
Leqvio (inclisiran, KJX839) is the first and only small interfering RNA (siRNA) therapy to reduce low-density lipoprotein cholesterol (LDL-C) levels via an RNA interference (RNAi) mechanism of action and could help improve outcomes for patients with atherosclerotic cardiovascular disease (ASCVD), a deadly form of cardiovascular disease5,7,14. With two doses a year** and effective and sustained LDL-C reduction, Leqvio works as a complement to statins5,7. Leqvio works differently from other therapies by preventing the production of the target protein in the liver, increasing hepatic uptake of LDL-C and clearing it from the bloodstream14. Leqvio is dosed initially, again at three months and then once every six months5,7. In three clinical trials, patients taking Leqvio maintained LDL-C reduction throughout each six-month dosing interval7,9. Administered in-office as a subcutaneous injection, Leqvio is expected to integrate seamlessly into a patient’s healthcare routine5,7.

In the Phase III trials, Leqvio was well-tolerated. The most common adverse events reported (?3% of patients treated with Leqvio and occurring more frequently than placebo) were injection site reaction, arthralgia, urinary tract infection, diarrhea, bronchitis, pain in extremity and dyspnea. Among those, injection site reactions were the most frequent ones. Those were generally mild, and none were severe or persistent.

Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

Disclaimer
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