LEQVIO®, A FIRST-IN-CLASS siRNA THERAPY FOR LDL-C LOWERING, NOW LISTED ON THE PBS

• Approval based on results from the pivotal Phase III ORION-9, -10 and -11 clinical trials.^1-2
• With two maintenance doses a year, after an initial dose and one at three months, Leqvio is the first and only small interfering RNA (siRNA) therapy for low-density lipoprotein-cholesterol (LDL-C) reduction approved in Australia.^1-3
• CVD remains one of Australia’s leading causes of death.⁴ In 2021, CVD was responsible for 600,000 hospitalisations and 42,700 deaths.⁵

2 APRIL 2024, Sydney: Novartis Australia welcomes the listing of Leqvio® (inclisiran) on the Pharmaceutical Benefits Scheme (PBS) for the treatment of patients with heterozygous familial hypercholesterolaemia (HeFH) and non-familial hypercholesterolaemia (non-FH) with atherosclerotic cardiovascular disease (ASCVD), who have additional cardiovascular risk factors, and who are unable to achieve target lipid thresholds with statins, if tolerated, and ezetimibe.

Leqvio is the first and only small interfering RNA (siRNA) therapy to lower LDL-C. The first in class therapy only requires two doses a year, after an initial dose and one at three months. Leqvio works by improving the liver’s natural ability to prevent the production of a protein that plays a key role in keeping cholesterol circulating in the system.^6-7

This reduces the amount of LDL-C or ‘bad cholesterol’ in the bloodstream.^6-7

“Cardiovascular disease represents a significant public health burden, with a quarter of all deaths in Australia attributable to CVD as an underling cause, and one in three Australian adults living with high cholesterol levels,” said Dr Karam Kostner, Associate Professor of Medicine at the University of Queensland and Director of Cardiology at Mater Hospital, Brisbane.

“The availability of a first-of-its-kind siRNA therapy that only requires twice-yearly dosing provides patients with another highly effective treatment option to help them control their LDL-C levels. This is a fantastic and welcome development in an area of high unmet need”.

ASCVD occurs when plaques made up of fat, cholesterol, calcium and other substances build up in the walls of arteries. This causes the arteries to harden, thicken, restrict blood flow and in some cases cause blood clots.^8-9

ASCVD can also cause cardiovascular events like heart attacks and strokes.^9-10

"The introduction of a new treatment option is wonderful news for Australian patients. Continued innovation in the area of hypercholesterolaemia and atherosclerotic cardiovascular disease and timely access to the right treatment is essential for people living with these conditions.” said Tanya Hall, Founder and Chief Executive Officer at the leading patient organisation, Hearts4Heart.

Matt Zeller, Country President Novartis Australia and New Zealand said, “The impact of CVD in Australia is devastating, claiming one life every 12 minutes. Now, Leqvio is available on the PBS and this first-in-class treatment option has the potential to transform patient care and help improve the lives of individuals living with CVD.”

“We are committed to partnering with all stakeholders across the healthcare ecosystem to ensure patients will be able to access Leqvio in a timely manner, no matter where they live. Given the increased burden on our healthcare system and the inequalities often faced by rural and regional patients, we believe that pharmacists can also play a key role in helping patients administer and manage the therapy,” said Zeller.

The approval is based on results from the pivotal Phase III ORION-9, -10 and -11 clinical trials.^1-2

Please review the full Consumer Medicines Information for Leqvio® here – https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-CMI-01299-1&d=20240226172310101

For media enquiries please contact:

This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

PBS Information: Authority Required (telephone/online) for patients with hypercholesterolaemia. Refer to PBS schedule for full Authority information.

References

1. Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507-1519. Accessed February 2024. Available at: https://doi.org/10.1056/NEJMoa1912387
2. Raal FJ, Kallend D, Ray KK, et al. Inclisiran for heterozygous familial hypercholesterolemia. N Engl J Med. 2020;382(16):1520-1530. Accessed February 2024. Available at: https://doi.org/10.1056/NEJMoa1913805
3. Leqvio Consumer Medicine Information.
4. Heart Research Institute (HRI). Heart disease remains leading cause of death in Australia. . Accessed February 2024. Available at: https://www.hri.org.au/news/heart-disease-remains-leading-cause-of-death-in-australia
5. Australian Institute of Health and Welfare. Heart, stroke and vascular disease: Australian facts. Accessed February 2024. Available at: https://www.aihw.gov.au/reports/heart-stroke-vascular-disease/hsvd-facts/contents/about
6. Khvorova A. Oligonucleotide therapeutics—a new class of cholesterol-lowering drugs. N Engl J Med. 2017;376(1):4-7. Accessed February 2024. Available at: https://doi.org/10.1056/NEJMp1614154
7. Kosmas CE, Muñoz Estrella A, Sourlas A, et al. Inclisiran: a new promising agent in the management of hypercholesterolemia. Diseases. 2018;6(3):63. Accessed February 2024. Available at: https://doi.org/10.3390/diseases6030063
8. Johns Hopkins Medicine. What is atherosclerosis?. Accessed February 2024. Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/atherosclerosis
9. Heart Research Institute (HRI). Atherosclerosis: causes and risk factors. Accessed February 2024. Available at: https://hri.org.au/health/learn/cardiovascular-disease/atherosclerosis-causes-and-risk-factors
10. Pahwa R, Jialal I. Atherosclerosis. [Updated 2023 Aug 8]. Accessed February 2024. Available at: https://www.ncbi.nlm.nih.gov/books/NBK507799/
11. Food and Drug Administration (FDA). Leqvio. Last updated July 2023. Accessed February 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214012s009lbl.pdf
12. European Medicines Agency (EMA). Leqvio. Last updated December 2020. Accessed February 2024. Available at: https://www.ema.europa.eu/en/documents/overview/leqvio-epar-medicine-overview_en.pdf
13. Novartis. Media release. 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. Accessed February 2024. Available at: https://www.novartis.com/us-en/news/media-releases/us-fda-approves-expanded-indication-novartis-leqvio-inclisiran-include-treatment-adults-high-ldl-c-and-who-are-increased-risk-heart-disease
14. National Medical Products Administration (NMPA). August 23 Drug Approval Information. Accessed February 2024. Available at: https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20230824155809182.html
15. Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell. 2015;161(1):161-172.
16. 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.
17. World Health Organization (WHO). Cardiovascular diseases (CVDs). Published June 2021. Accessed February 2024. Available at: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
18. 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.
19. 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.
20. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.
21. World Health Organization (WHO). Fact sheet. Non-communicable diseases. Published June 2018. Accessed February 2024. Available at: https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases
22. World Health Organization (WHO). Cardiovascular diseases: Avoiding heart attacks and strokes. Published September 2015. Accessed February 2024. Available at: https://www.who.int/news-room/questions-and-answers/item/cardiovascular-diseases-avoiding-heart-attacks-and-strokes

About Leqvio

Leqvio is a subcutaneous injection given by a health care provider with an initial dose, another at three months, and then every six months.^11-12 As a twice-yearly, HCP-administered treatment, Leqvio may help to circumvent the challenges of treatment adherence, a common issue in cholesterol management.^{1-2, 13} Leqvio is approved in more than 80 countries worldwide including the US, EU and China.^{11-12, 14}

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.

About atherosclerotic cardiovascular disease (ASCVD)

Atherosclerotic cardiovascular disease (ASCVD) refers to a variety of diseases caused by the development and growth of plaques in the inner lining of the arteries.¹⁵ The atherosclerotic plaque is mainly composed of low-density lipoprotein cholesterol (LDL-C) which accumulates over time.¹⁵ Cumulative exposure to LDL-C is proportionally related to arterial plaque growth and progression leads to subsequent risk of cardiovascular events such as a heart attack or stroke.^15-16 Accounting for 85% of all cardiovascular disease deaths, ASCVD is the primary cause of mortality in the European Union and its burden in the United States is greater than that from any other chronic diseases.^17-20 ASCVD risk-equivalent corresponds to conditions that confer a similar risk for an ASCVD event (e.g., diabetes, heterozygous familial hypercholesterolemia).^{1, 20}

About Novartis in Cardiovascular Cardiovascular (CV) disease is a global health crisis.^{17, 21} CV disease is the number one killer in the world.¹⁷ Taking more lives than all cancers combined, it contributes to one in every three deaths globally.^{17, 21} Of all CV events, 80% can be prevented.²² Patients and their families deserve better, and our society deserves more.

Thanks to a combination of our legacy, global footprint and leading science, Novartis is uniquely positioned to help change this landscape. We are transforming the way we think about how CV disease is managed throughout life. Our efforts include the use of early interventions and the development of pioneering treatments that address the spectrum of CV disease, from prevention to management, as well as the creation of innovative access models. By re-writing the way we work with society, we will lead a worldwide effort to improve health outcomes and roll back the crisis of CV death.

About Novartis

Novartis is reimagining medicine to improve and extend people’s lives. We deliver high-value medicines that alleviate society’s greatest disease burdens through technology leadership in R&D and novel access approaches. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. About 103,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world.

Novartis Pharmaceuticals Australia Pty Ltd, 54 Waterloo Road Macquarie Park NSW 2113. Telephone 1800 671 203. ABN 18004 244 160. Date of preparation: February 2024. AU-25793.