Novartis Announces EU Approval of First-in-Class siRNA Therapy Inclisiran (Leqvio®) for Hypercholesterolemia and Mixed Dyslipidemia
Dec 11, 2020 17:13
CST Updated
17:13
Novartis
Drug Development and Manufacturing
European Commission
The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.
Alnylam Pharmaceuticals
RNA Interference (RNAi) Innovative Drug Developer
Novartis Announces European Commission (EC) Approval of Inclisiran (Leqvio®) for the Treatment of Adult Hypercholesterolemia and Mixed DyslipidemiaThis approval is based on robust data from the ORION clinical studies. The study results demonstrated that Inclisiran achieved a 52% reduction in LDL-C in patients who failed to reach their LDL-C targets despite treatment with maximally tolerated statin therapy.1,2. The dosing regimen of inclisiran, which requires only two injections per year after the initial doses at baseline and month 3, is expected to address the challenge of long-term patient adherence.1-3。
Cardiovascular disease remains the leading cause of death worldwide; despite the widespread use of statins, 80% of high-risk patients still fail to achieve the LDL-C target levels recommended by guidelines.4-7Inclisiran is a first-in-class small interfering RNA (siRNA) therapeutic that provides sustained and effective reduction of LDL-C levels. It is indicated for patients with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, and heterozygous familial hypercholesterolemia (HeFH). These conditions are the leading causes of myocardial infarction and stroke, which can ultimately result in death.1-3。
Professor Ulf Landmesser, MD, Director of the Charité Center for Cardiovascular Diseases in Berlin, stated: “Long-term, persistent exposure to high levels of LDL-C increases the risk of ASCVD.”8, which may lead to cardiovascular events such as myocardial infarction and stroke. As the first and only siRNA drug in the cardiovascular field, Inclisiran can sustainably and effectively lower LDL-C levels, holding promise to transform the therapeutic approach to LDL-C lowering. With only two injections required per year, this drug has the potential to fundamentally address challenges related to treatment adherence, thereby improving treatment rates and compliance.”
Marie-France Tschudin, Global President of Novartis, stated: “Cardiovascular disease remains the leading cause of death to date.”4This underscores the urgent need for innovative therapies among patients whose LDL-C levels are not at target. We are proud to introduce inclisiran, a first-in-class agent that effectively and sustainably lowers LDL-C levels, holding substantial potential to improve treatment outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). Novartis remains committed to collaborating with healthcare systems and relevant partners to envision the future of cardiovascular disease treatment, explore innovative and accessible therapies, and accelerate the arrival of a turning point in reducing cardiovascular events.”
Inclisiran Approved in Combination with Dietary Therapy for the Treatment of Primary Hypercholesterolemia (Including Heterozygous Familial and Non-Familial) and Mixed Dyslipidemia in Adults:
· For patients whose LDL-C levels remain uncontrolled despite treatment with the maximum tolerated dose of statins, combination therapy with statins or other lipid-lowering therapies may be used.
· For patients who are intolerant to statins or have contraindications to their use, Inclisiran can be used as monotherapy or in combination with other lipid-lowering therapies.
Currently, inclisiran is also under review by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with high levels of LDL-C despite receiving maximally tolerated statin therapy.
Note: The drug inclisiran mentioned in this article has not yet been approved in mainland China.
References
1. Raal F, Kallend D, Ray K, et al. Inclisiran for Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020;382(16):1520–1530.
2. Ray K, Wright R, 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.
3. Stoekenbroek RM, Kallend D, Wijngaard PL, et al. Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program. Future Cardiol. 2018;14(6):433–442.
4. European Heart Network. European Cardiovascular Disease Statistics 2017 edition. Available from: http://www.ehnheart.org/cvd-statistics/cvd-statistics-2017 [Last accessed: November 2020].
5. Bruckert E, Parhofer KG, Gonzalez-Juanatey JR, et al. Proportion of High-Risk/Very High-Risk Patients in Europe with Low-Density Lipoprotein Cholesterol at Target According to European Guidelines: A Systematic Review. Adv Ther. 2020;37(5):1724–1736.
6. Lansberg P, Lee A, Lee ZV, et al. Nonadherence to statins: individualized intervention strategies outside the pill box. Vasc Health Risk Manag. 2018;14:91–102.
7. Wong ND, Young D, Zhao Y, et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011–2012. J Clin Lipidol. 2016;10(5):1109–1118.
8. 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.
Cardiovascular disease remains the leading cause of death worldwide; despite the widespread use of statins, 80% of high-risk patients still fail to achieve the LDL-C target levels recommended by guidelines.4-7Inclisiran is a first-in-class small interfering RNA (siRNA) therapeutic that provides sustained and effective reduction of LDL-C levels. It is indicated for patients with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, and heterozygous familial hypercholesterolemia (HeFH). These conditions are the leading causes of myocardial infarction and stroke, which can ultimately result in death.1-3。
Professor Ulf Landmesser, MD, Director of the Charité Center for Cardiovascular Diseases in Berlin, stated: “Long-term, persistent exposure to high levels of LDL-C increases the risk of ASCVD.”8, which may lead to cardiovascular events such as myocardial infarction and stroke. As the first and only siRNA drug in the cardiovascular field, Inclisiran can sustainably and effectively lower LDL-C levels, holding promise to transform the therapeutic approach to LDL-C lowering. With only two injections required per year, this drug has the potential to fundamentally address challenges related to treatment adherence, thereby improving treatment rates and compliance.”
Marie-France Tschudin, Global President of Novartis, stated: “Cardiovascular disease remains the leading cause of death to date.”4This underscores the urgent need for innovative therapies among patients whose LDL-C levels are not at target. We are proud to introduce inclisiran, a first-in-class agent that effectively and sustainably lowers LDL-C levels, holding substantial potential to improve treatment outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). Novartis remains committed to collaborating with healthcare systems and relevant partners to envision the future of cardiovascular disease treatment, explore innovative and accessible therapies, and accelerate the arrival of a turning point in reducing cardiovascular events.”
Inclisiran Approved in Combination with Dietary Therapy for the Treatment of Primary Hypercholesterolemia (Including Heterozygous Familial and Non-Familial) and Mixed Dyslipidemia in Adults:
· For patients whose LDL-C levels remain uncontrolled despite treatment with the maximum tolerated dose of statins, combination therapy with statins or other lipid-lowering therapies may be used.
· For patients who are intolerant to statins or have contraindications to their use, Inclisiran can be used as monotherapy or in combination with other lipid-lowering therapies.
Currently, inclisiran is also under review by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with high levels of LDL-C despite receiving maximally tolerated statin therapy.
Note: The drug inclisiran mentioned in this article has not yet been approved in mainland China.
References
1. Raal F, Kallend D, Ray K, et al. Inclisiran for Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020;382(16):1520–1530.
2. Ray K, Wright R, 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.
3. Stoekenbroek RM, Kallend D, Wijngaard PL, et al. Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program. Future Cardiol. 2018;14(6):433–442.
4. European Heart Network. European Cardiovascular Disease Statistics 2017 edition. Available from: http://www.ehnheart.org/cvd-statistics/cvd-statistics-2017 [Last accessed: November 2020].
5. Bruckert E, Parhofer KG, Gonzalez-Juanatey JR, et al. Proportion of High-Risk/Very High-Risk Patients in Europe with Low-Density Lipoprotein Cholesterol at Target According to European Guidelines: A Systematic Review. Adv Ther. 2020;37(5):1724–1736.
6. Lansberg P, Lee A, Lee ZV, et al. Nonadherence to statins: individualized intervention strategies outside the pill box. Vasc Health Risk Manag. 2018;14:91–102.
7. Wong ND, Young D, Zhao Y, et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011–2012. J Clin Lipidol. 2016;10(5):1109–1118.
8. 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.