Novartis twice-yearly* Leqvio® demonstrated clinically meaningful, statistically significant LDL-C lowering as a monotherapy in patients at low or moderate ASCVD risk

• Phase III V-MONO study met its primary endpoints, demonstrating superiority of Leqvio (inclisiran) monotherapy vs both placebo and ezetimibe in LDL-C reduction¹

• Results add to growing body of evidence for Leqvio across the ASCVD continuum

• Data will be shared with regulatory agencies and presented at an upcoming medical meeting

• V-MONO is part of the 60,000-patient VictORION clinical trial program assessing Leqvio for primary and secondary ASCVD prevention

Basel, August 28, 2024 – Novartis announced today positive topline results from twice-yearly* Leqvio^® (inclisiran) in the Phase III V-MONO study, which met its primary endpoints. Leqvio monotherapy achieved clinically meaningful and statistically significant low-density lipoprotein cholesterol (LDL-C) lowering versus both placebo and ezetimibe in patients who were at low or moderate risk of developing atherosclerotic cardiovascular disease (ASCVD) and not receiving lipid-lowering therapy¹.

V-MONO is the first trial evaluating a small interfering RNA (siRNA) therapy taken as monotherapy to lower LDL-C in patients at low or moderate risk of developing ASCVD. Novartis plans to present results from this trial at an upcoming medical meeting and share with regulatory agencies including the US Food and Drug Administration (FDA).

“We are proud that we continue to advance the scientific understanding of using siRNA therapy to tackle one of the world’s biggest healthcare challenges, as too many people still struggle to reach their cholesterol goals,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “This trial adds to the growing body of evidence for Leqvio across the full spectrum of ASCVD as we strive to help more patients in need.”

Novartis continues to advance multiple studies evaluating the potential use of Leqvio across primary and secondary prevention. VICTORION-1-PREVENT (V1P) is the only dedicated study of a non-statin lipid-lowering therapy in a high-risk primary prevention population as defined by American College of Cardiology (ACC) and American Heart Association (AHA) guidelines; this outcomes study is expected to complete enrollment later this year². In the secondary prevention setting, the ORION-4 and VICTORION-2-PREVENT (V2P) outcomes studies remain on track for data readouts in 2026 and 2027, respectively.

*After an initial dose and another at three months.

About V-MONO
V-MONO (CKJX839D12304) is a 6-month randomized, double-blind, placebo- and active-comparator controlled Phase III study to evaluate the efficacy of Leqvio as monotherapy in patients at low or moderate risk of developing ASCVD who are not receiving lipid-lowering therapy³. A total of 350 patients were randomized in a 2:1:1 ratio to inclisiran (n=174), ezetimibe (n=89) or placebo (n=87). The primary endpoints were the percent change in LDL-C from baseline to Day 150 with Leqvio versus placebo and ezetimibe.

About VictORION
The V-MONO study is part of VictORION, a clinical trial program to expand the foundational evidence of LDL-C reduction with Leqvio in diverse patient populations through randomized clinical trials, implementation research, real-world evidence, and primary and secondary prevention trials assessing the potential benefits of Leqvio on cardiovascular outcomes. The VictORION program is one the largest clinical trial programs of its kind, enrolling over 60,000 patients in more than 50 countries worldwide across more than 30 trials, including ORION-4 (secondary prevention), V-2-PREVENT (secondary prevention), V-1-PREVENT (high-risk primary prevention), V-INCEPTION and V-INCLUSION.

About Leqvio
Leqvio is the first and only small interfering RNA (siRNA) therapy to lower LDL-C. It is a subcutaneous injection given by a healthcare provider (HCP) with an initial dose, another at three months, and then every six months^4,5. As a twice-yearly, HCP-administered treatment, Leqvio may help to circumvent the challenges of treatment adherence, a common issue in cholesterol management.

Leqvio is approved in nearly 100 countries, including the US, EU, Japan and China^,4-7. Novartis obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

About Atherosclerotic Cardiovascular Disease (ASCVD)
Cardiovascular disease (CVD) affects hundreds of millions of people and claims more lives globally than cancer, chronic lung disease and diabetes combined⁸. Around 80% of premature cardiovascular deaths can be prevented by addressing factors that cause or worsen CVD⁹.

ASCVD accounts for 85% of all CV deaths^10-13. It is the primary cause of mortality in the European Union and its burden in the US is greater than that of any other chronic diseases^10-13. ASCVD is caused by the development and growth of plaques in the inner lining of the arteries¹⁴. The atherosclerotic plaque is mainly composed of low-density lipoprotein cholesterol (LDL-C) that accumulates over time¹⁵. Cumulative exposure to LDL-C can increase one’s risk of cardiovascular events such as a heart attack or stroke^14,15.

About Novartis in Cardiovascular Disease
At Novartis, our mission is to ensure no heart is lost too soon. We envision a world where preventable CV deaths are no longer part of our lives. We’re proud of the positive impact we’ve made over the past 40 years and remain dedicated to tackling the most challenging problems in CVD. Through cutting-edge science and technology, we are advancing the next generation of medicines for hypertension, hyperlipidemia, and heart failure and are pioneering breakthroughs for genetic risk factors. We also work with patients, healthcare professionals, and organizations around the world to improve CV care beyond medicines alone. Together, we can help people with CVD enjoy longer, healthier lives and more time with their loved ones.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.

References

1. Data on file. Study NCT05763875. Novartis Pharmaceuticals Corp; 2024.
2. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Journal of the American College of Cardiology. 2019;74(10):e177-e232. doi:https://doi.org/10.1016/j.jacc.2019.03.010
3. ClinicalTrials.gov. NCT05763875. Accessed August 21, 2024. https://clinicaltrials.gov/study/NCT05763875
4. Leqvio. Summary of Product Characteristics. Novartis.
5. Leqvio. Prescribing information. Novartis Pharmaceuticals Corp.
6. National Medical Products Administration. Drug approval document delivery information. Published August 24, 2023. Accessed March 12, 2024. https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20230824155809182.html
7. Pharmaceutical and Medicinal Devices Agency Japan. New drugs approved in FY 2023 document. Accessed August 21, 2024. https://www.pmda.go.jp/files/000269225.pdf
8. American Heart Association. More than half of U.S. adults don’t know heart disease is leading cause of death, despite 100-year reign. Published January 24, 2024. Accessed August 21, 2024. https://newsroom.heart.org/news/more-than-half-of-u-s-adults-dont-know-heart-disease-is-leading-cause-of-death-despite-100-year-reign
9. World Heart Federation. World Heart Report. Published May 20, 2023. Accessed August 21, 2024. https://world-heart-federation.org/wp-content/uploads/World-Heart-Report-2023.pdf
10. World Health Organization. Cardiovascular diseases (CVDs). Published June 11, 2021. Accessed August 21, 2024. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
11. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220. 
12. Kim H, Kim S, Han S, et al. Prevalence and incidence of atherosclerotic cardiovascular disease and its risk factors in Korea: a nationwide population-based study. BMC Public Health. 2019;19(1):1112. 
13. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082–e1143. 
14. Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell. 2015;161(1):161-172. 
15. Ference BA, Graham I, Tokgozoglu L, Catapano AL. Impact of lipids on cardiovascular health: JACC Health Promotion Series. J Am Coll Cardiol. 2018;72(10):1141-1156. 

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