MUNICH--(BUSINESS WIRE)--Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) announced today new data presented at the European Society of Cardiology Congress 2022 from its multinational prospective, observational study, SANTORINI across 14 countries.5 New simulation data adds to the growing body of evidence that indicates that maximising oral combination therapies by using ezetimibe and bempedoic acid after statins, might result in significantly more patients attaining European-guideline recommended LDL- goals and thereby potentially reducing their risk of cardiovascular events.2,4,6
Simulation of LCL-C risk reduction
Through simulation, researchers investigated the addition of bempedoic acid to ezetimibe in the treatment pathway for patients at high- and very high-risk of cardiovascular events due to hypercholesterolaemia using the SANTORINI data, to assess the proportion of patients who might reach their European-guideline recommended lipid goals. The data presented today indicate that of those patients on ezetimibe and not currently at goal, the addition of bempedoic acid is projected to result in another 36% (n=1222/3412) goal achievement.2
The analysis included a cohort of 6177 patients who were receiving any known LLT regimen with LDL-C data and known CV risk status at the SANTORINI baseline.2 A treatment algorithm was applied to those not at their risk-based LDL-C goals at baseline by first adding ezetimibe if not already and subsequently bempedoic acid if they were not at goal.2 Patients on PCSK9i inhibitors were not used in the simulation steps irrespective of goal achievement.2 The effect of treatment on LDL-C levels was simulated through a Monte Carlo simulation run 10,000 times.2 LDL-C reductions associated with ezetimibe and bempedoic acid treatment were based on probabilistic distributions sourced from clinical trial efficacies based on published studies.2
Overall, the number of patients at the European guideline recommended goal would be expected to increase from 1,428 (23.1%) at baseline to 2,455 (39.7%) and 3,677 (59.5%) after addition of ezetimibe and bempedoic acid, sequentially.2 Furthermore, the mean LDL-C for the whole cohort would be expected to fall through this pathway from 80.33 mg/dL at baseline to 69.28 mg/dL and 60.94 mg/dL, respectively.2
The 2019 ESC/EAS management of dyslipidaemia guidelines recommend that the LDL-C goals for treating patients at high- and very high-risk of CV events are <1.8 mmol/L and <1.4 mmol/L, respectively.4 However, previous research from the SANTORINI registry show that only 20.1% of patients had achieved their risk-based LDL-C goal, with mean LDL-C levels reported in the clinical setting as 2.41 mmol/L - much higher than European guideline recommendations.3,4 For those patients who remain at high residual risk of CV events due to elevated LDL-C levels, the guidelines recommend more intense treatment, including use of combination therapy.4
The simulation data presented today adds to the growing body of evidence that optimising use of bempedoic acid in addition to ezetimibe could result in significantly more patients attaining recommended lipid goals and thereby reducing their risk of atherosclerotic cardiovascular disease.2
“This is the first simulation data from the SANTORINI registry that allows us to assess the proportion of patients who might reach LDL-C goal with the addition of bempedoic acid to existing treatment algorithms,” said Professor Kausik Ray, Professor of Public Health and President of the European Atherosclerosis Society, Honorary Consultant Cardiologist, Director ICTU Global and Deputy Director of the Imperial Clinical Trials Unit at Imperial College London, and Principal Investigator of SANTORINI. “We know that many at-risk patients are still not achieving their recommended goals, and today’s data reinforces recommendations from guidelines that we must intensify treatment for those at the highest levels of risk for heart attacks and strokes. The simulation data provides a positive indication of how we can better help our patients to achieve their LDL-C goals in clinical practice and ultimately improve their outcomes.”
CV risk factors in patients with and without a history of atherosclerotic cardiovascular disease (ASCVD)
In another sub-analysis from the SANTORINI registry of 9,044 patients, those patients whose CV risk was classified by the investigator based on the 2019 ESC/EAS guidelines was re-assessed centrally based on the data present in the study database.1 Overall, ESC/EAS guidelines were most commonly used basis for risk classification (52.0%).1,4 Among all patients, the investigator assessed 26.0% and 84.2% of patients without and with atherosclerotic CVD (ASCVD), respectively, as being very high-risk.1 In contrast, central re-estimation for those using ESC/EAS guidelines suggested that 54.7% and 100% of those without and with ASCVD were at very high-risk.1,4
CV risk factors or ASCVD were common in the SANTORINI study patients.1 Hypertension was the most common risk factor in both those with and without ASCVD, whereas diabetes and familial hypercholesterolaemia were most prevalent in patients without versus those with ASCVD (44.6% vs 30.3% and 18.6% vs 7.2%, respectively).1 Managing ASCVD is related to individual risk factors; the higher the risk the more intense the intervention required.4 Therefore, it is crucial to accurately identify the level of risk to ensure a tailored solution for ASCVD prevention and reduce the impact among patients.
“SANTORINI data presented during the ESC congress shows the CV risk of patients both with, and without, ASCVD is underestimated in clinical practice, potentially limiting the prevention of ASCVD across Europe.1” said Dr Stefan Seyfried, Vice President Medical Affairs Specialty Medicines, Daiichi Sankyo Europe GmbH, who added, “At Daiichi-Sankyo Europe, we understand the need to support and work with the clinical community to continue to embed the EAS/ESC guidelines into routine clinical practice. We are committed to working alongside clinicians to help reduce the number of lives that are affected by CVD every day by exploring the true impact of CVD in clinical care, through studies such as SANTORINI.”
The SANTORINI study is a multinational, prospective, observational study that enrolled 9,606 patients from over 800 sites in 14 countries across Europe. The primary objective is to document, in the real-world setting, the effectiveness of current treatment modalities in managing plasma levels of LDL-C in high- and very high-risk patients requiring lipid-lowering therapies. The study population consists of high- and very high-risk patients previously diagnosed and treated as well as newly diagnosed and requiring treatment.
Only data from routine clinical practice will be documented and physicians will not be required to perform any mandatory assessment outside the routine clinical practice. To facilitate accurate recording of data, patients can optionally fill in a memory aid to note important details. Completion of the SANTORINI study is anticipated in Q1 2023.
About bempedoic acid
Bempedoic acid (commercialised in the European Economic Area, Turkey and Switzerland as NILEMDO®▼7) is a first-in-class, oral treatment which lowers cholesterol, and which can be combined with other oral treatments to help lower cholesterol even further. Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme which is involved in the production of cholesterol in the liver.
Bempedoic acid has been approved for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:
- in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or
- alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
Bempedoic acid acts on the well-known cholesterol synthesis pathway, upstream of the statin target in the liver, which allows additional LDL-C lowering when added to statin or other lipid-lowering therapies. Due to its unique mechanism of action, bempedoic acid is not activated in skeletal muscle.
Daiichi Sankyo Europe has licensed exclusive commercialisation rights to bempedoic acid in the European Economic Area, Turkey and Switzerland from Esperion and is the full Marketing Authorisation Holder in these territories.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.”
For more information, please visit www.daiichisankyo.com
▼ This medicinal product is subject to additional monitoring.
1 Ray, KK., et al. Cardiovascular risk factors in patients with and without a history of atherosclerotic cardiovascular disease in the SANTORINI study and estimation of risk. ePoster at the European Society of Cardiology 2022. Poster- 82567
2 Ray, KK., et al. Simulation of bempedoic acid in the lipid-lowering treatment pathway using the European contemporary SANTORINI cohort of high- and very high-risk patients. ePoster at European Society of Cardiology 2022 Abstract- 83386
3 Ray, KK, et al. Cardiovascular risk assessment by physicians and lipid-lowering therapy prescribing in high- and very high-risk patients: results from the multinational observational SANTORINI study. Poster 335 presented at the European Atherosclerosis Society (EAS) 2022.
4 Mach, F., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2019. 00: 1–78.
5 ClinicalTrials.gov. Treatment of High and Very High riSk Dyslipidemic pAtients for the PreveNTion of CardiOvasculaR Events (SANTORINI). Available at: https://clinicaltrials.gov/ct2/show/NCT04271280. Last accessed August 2022.
6 Blaum, C., et al. Target Populations and Treatment Cost for Bempedoic Acid and PCSK9 Inhibitors: A Simulation Study in a Contemporary CAD Cohort. Clinical Therapeutics. 2021: 43:9 1583-1600.
7 European Medicines Agency. NILEMDO Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/nilemdo-epar-product-information_en.pdf. Last accessed August 2022