Novartis Showcases Innovative Lipid-Lowering Therapy Pelacarsen at CIIE for the First Time

On November 9, 2023, at the 6th China International Import Expo, Novartis, a globally 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 to effectively reduce Lp(a) levels. It provides more innovative treatment options for clinical disease prevention and control, supporting cardiovascular health management in China.

Novartis CIIE Booth
New Target for Independent Cardiovascular Disease Risk Factor Lp(a): Guidelines Recommend At Least One Test in a Lifetime
With the intensification of the aging population problem and changes in lifestyle, cardiovascular diseases in China are showing a large base of patients and a rapid increase in the number of cases. In 2022, the number of people suffering from cardiovascular diseases in China has risen to 330 million1,2. Atherosclerotic cardiovascular disease (ASCVD), such as ischemic heart disease and ischemic stroke, is the leading cause of death among urban and rural residents in China, accounting for more than 40% of the causes of death3. It has become one of the most serious chronic diseases threatening people's life and health, with a continuously increasing disease burden. Lipid management is urgently needed4.

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 results have found that there are still new targets affecting cardiovascular event risks. 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.

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 Guideline for Lipid Management (2023)" indicates 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.

Lipoprotein (a)
Lipid Testing is the Foundation for Detecting Dyslipidemia, Assessing ASCVD Risk, and Determining Intervention Strategies. In addition to routine lipid index testing, multiple academic guidelines and consensus documents both in China and internationally recommend 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 Its 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 categories of populations: those at extremely high risk of ASCVD, individuals with a family history of premature ASCVD, first-degree relatives with elevated serum Lp(a) levels >90 mg/dl (200 nmol/L), patients with familial hypercholesterolemia (FH) or other hereditary dyslipidemias, and those with calcific aortic valve stenosis (CAVS). Lp(a) levels can be measured by including the relevant test items in the lipid profile.

Reducing Serum Lp(a) Levels: A New Lipid-Lowering Therapy Paves the Way for Cardiovascular Prevention

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 are unable to reduce Lp(a) to a level that achieves 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.
Pelacarsen, an antisense oligonucleotide drug exhibited by Novartis at this year's CIIE, is a novel lipid-lowering therapy that specifically 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 lipoprotein(a) protein and suppressing the synthesis of Lp(a), thereby effectively reducing Lp(a) levels in plasma. Phase II clinical trial data for Pelacarsen shows it can reduce Lp(a) by 80%. A monthly dose of 80mg can lower Lp(a) levels to below 50 mg/dL in 98% of patients, offering significant potential benefits in cardiovascular prevention and treatment.

Pelacarsen

Novartis China President Zhang Ying stated: "Novartis is committed to patient-centeredness and continuously innovating to develop high-value pharmaceutical products 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 the future approval and launch of this product in China, simultaneously with the rest of the world, benefiting a wide range of Chinese patients."
About Pelacarsen
Pelacarsen is an antisense oligonucleotide drug targeting Apo(a) mRNA, and it has the potential to become the first effective novel lipid-lowering drug to reduce lipoprotein(a). Phase 2 clinical trial data 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.
References:
1. Writing Group of the Report on Cardiovascular Health and Diseases in China: "Summary of Cardiovascular Health and Diseases in China 2022", Chinese Circulation Journal, 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 China's Lipid Management Guidelines, Li Jianjun, Zhao Shuiping, et al. China's 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.