Novartis Unveils Innovative Lp(a)-Targeting Therapy Pelacarsen at CIIE, Pioneering New Frontier in Cardiovascular Disease Prevention

ShanghaiNovember 9, 2023PR Newswire -- At the 6th China International Import Expo, Novartis, a global leading innovative pharmaceutical company, showcased its innovative lipid-lowering therapy, Pelacarsen, for the first time. As an antisense oligonucleotide drug targeting lipoprotein(a) [Lp(a)], a potential target for cardiovascular diseases, Pelacarsen can inhibit the synthesis of Lp(a), and is expected to become the first innovative lipid-lowering drug that effectively reduces Lp(a) levels. It will provide more innovative treatment options for clinical disease prevention and control, and help with the cardiovascular health management of the Chinese people.

Novartis CIIE Booth

Independent Risk Factors for Cardiovascular DiseaseNew Target for Lp(a): Guidelines Recommend at Least One Test in a Lifetime

With the aggravation of the aging population problem and changes in lifestyle, cardiovascular diseases in China have shown a trend of a large base of patients and a rapid increase in the number of patients. In 2022, the number of people suffering from cardiovascular diseases in China has risen to 330 million.^[1],[2]Cardiovascular diseases, mainly atherosclerotic cardiovascular disease (ASCVD) such as ischemic heart disease and ischemic stroke, are the leading cause of death among urban and rural residents in China, accounting for more than 40% of all deaths.^[3], has become one of the most serious chronic diseases threatening people's lives and health, with the disease burden continuously increasing. Lipid management is urgently needed.^[4]。

For a long time, low-density lipoprotein cholesterol (LDL-C) has been regarded as the primary target for lipid intervention in atherosclerotic cardiovascular disease (ASCVD), and is widely known as "bad cholesterol." Notably, relevant clinical research findings have discovered new targets that still influence the risk of cardiovascular events. Lipoprotein(a) [Lp(a)] is one of the potential new lipid intervention targets that has garnered significant attention in recent years due to substantial evidence.^[5]。

Lipoprotein(a) [Lp(a)] is primarily synthesized in the liver and consists of a low-density lipoprotein (LDL)-like particle and apolipoprotein(a) [Apo(a)]. The "Chinese Guidelines for Lipid Management (2023)" indicate that elevated Lp(a) is an independent risk factor for cardiovascular diseases such as coronary heart disease, ischemic stroke, peripheral vascular disease, coronary artery calcification, and calcific aortic valve stenosis. Particularly in atherosclerotic cardiovascular disease and calcific aortic valve stenosis, elevated Lp(a) can increase the risk of cardiovascular diseases through pro-atherosclerotic, pro-thrombotic, and pro-inflammatory mechanisms. Notably, serum Lp(a) concentration is mainly related to genetics and has little association with age or gender.

Lipid Testing is the Foundation for Identifying Lipid Abnormalities, Assessing ASCVD Risk, and Determining Intervention Strategies. In addition to routine lipid index testing, multiple academic guidelines and consensus recommendations both in China and internationally suggest that every adult should have their lipoprotein(a) [Lp(a)] levels tested at least once in their lifetime. The "Expert Scientific Recommendations on the Relationship Between Lipoprotein(a) and Cardiovascular Disease Risk and Clinical Management" indicate that when Lp(a) levels exceed 30 mg/dl, it signifies an increased ASCVD risk. It explicitly recommends testing serum Lp(a) levels in five groups: those at extremely high risk of ASCVD, individuals with a family history of premature ASCVD, first-degree relatives with serum Lp(a) levels elevated above 90 mg/dl (200 nmol/L), those with familial hypercholesterolemia (FH) or other hereditary dyslipidemias, and patients with calcific aortic valve stenosis (CAVS). Lp(a) levels can be measured by including relevant tests in the lipid profile.

Reduce SerumLp(a) Levels: New Lipid-Lowering Therapies Open Up a New Paradigm in Cardiovascular Prevention and Treatment

Since lipoprotein(a) [Lp(a)] levels are less influenced by acquired factors, lifestyle interventions such as healthy eating and exercise cannot directly reduce Lp(a) levels. Currently, there is no specific lipid-lowering therapy targeting Lp(a), and existing traditional lipid-lowering therapies cannot achieve a reduction in Lp(a) levels that would lead to significant therapeutic benefits. Therefore, targeted Lp(a) lipid-lowering therapy has become one of the key breakthroughs in the prevention and treatment of cardiovascular diseases.

The antisense oligonucleotide drug Pelacarsen exhibited by Novartis at this year's CIIE is a novel lipid-lowering therapy that targets the reduction of lipoprotein(a) [Lp(a)]. Pelacarsen enters hepatocytes and selectively cleaves the messenger RNA (mRNA) of Apo(a), inhibiting its translation into the protein of lipoprotein(a) and suppressing the synthesis of Lp(a), thereby effectively reducing the level of Lp(a) in plasma. Phase II clinical trial data for Pelacarsen shows that it can reduce Lp(a) by 80%, and a dosing regimen of 80mg/month can lower Lp(a) levels to below 50 mg/dL in 98% of patients.^[6]`, is expected to bring significant benefits in cardiovascular prevention and treatment.`

Novartis China President Zhang Ying stated: "Novartis is committed to patient-centered care and continuous innovation in the research and development of high-value pharmaceuticals and disease treatment solutions. In the field of cardiovascular diseases, we possess deep disease knowledge, a comprehensive product portfolio, and a robust future pipeline. The innovative therapy Pelacarsen showcased at this CIIE is another highly promising investigational product from Novartis in the cardiovascular field. It has received the 'Breakthrough Therapy Designation' from the National Medical Products Administration, and China has joined the global multi-center Phase III clinical trial for Pelacarsen. We look forward to this product being approved for marketing in China simultaneously with the rest of the world in the future, benefiting a wide range of Chinese patients."

AboutPelacarsen

Pelacarsen is an antisense oligonucleotide drug targeting Apo(a) mRNA, and it is expected to become the first novel lipid-lowering drug effective in reducing lipoprotein(a). Data from Phase 2 clinical studies show that Pelacarsen can reduce lipoprotein(a) by 80%, and a dosing regimen of 80mg/month can lower lipoprotein(a) levels to below 50 mg/dL in 98% of patients.Below.

References:

1. Writing Group of the Report on Cardiovascular Health and Diseases in China: "Summary of Cardiovascular Health and Diseases in China 2022," Chinese Journal of Circulation, 2023, Vol. 38, No. 6, p. 583.

2. Writing Group of "China Cardiovascular Health and Disease Report 2020": "Overview of China Cardiovascular Health and Disease Report 2020", China Cardiovascular Disease Research, 2021, Vol. 19, No. 7, p. 585.

3. National Center for Cardiovascular Diseases. Report on Cardiovascular Health and Diseases in China 2021[M]. Beijing: Science Press, 2022.

4. Joint Expert Committee for the Revision of Chinese Lipid Management Guidelines, Li Jianjun, Zhao Shuiping, et al. Chinese Lipid Management Guidelines (2023) [J]. Chinese Circulation Journal, 2023, 38(3):237-271.

5. Beijing Heart Society, Li Jianjun, Ma Changsheng. Expert Scientific Recommendations on the Relationship between Lipoprotein(a) and Cardiovascular Disease Risk and Clinical Management [J]. Chinese Circulation Journal, 2021, 36(12):10. DOI:10.3969/j.issn.1000-3614.2021.12.003.

6.《Lipoprotein(a) Reduction in Persons with Cardiovascular Disease》,N Engl J Med 2020; 382: e65 DOI: 10.1056/NEJMc2004861.

Disclaimer
1.Pelacarsen has not yet been approved in mainland China.
2. This material aims to provide relevant knowledge in the field of diseases and enhance the level of disease awareness, not for advertising purposes.
3. The information contained in this material is for reference only. Please follow the advice or guidance of doctors or other healthcare professionals.