Daiichi Sankyo Announces the Initiation of the Development of Oral Triple Combination Lipid-Lowering Tablets to Support the Management of LDL-C

Initiation of the development of new oral triple combination tablets, aimed at improving adherence and outcomes in low-density lipoprotein cholesterol (LDL-C) management. Recent findings from MILOS and SANTORINI registries presented at ESC Congress 2025, highlight ongoing challenges in accurately assessing cardiovascular (CV) risk and helping patients reach LDL-C targets.1-5 Furthermore, data from a four-country cohort of the MILOS study support the real-world effectiveness and safety of bempedoic acid in both sexes.6 Simulation using SANTORINI data reveals the potential of improved LDL-C goal attainment with tailored oral combination therapy of statins, ezetimibe and bempedoic acid, in line with the latest 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias.7,8 Daiichi Sankyo has a long-standing commitment to easing treatment of cardiovascular disease (CVD) and exploring new treatment options that improve CVD outcomes and treatment adherence.

Daiichi Sankyo Europe is pleased to announce the initiation of the development of new oral triple combination tablets in Europe of bempedoic acid, ezetimibe, and different doses of a statin (atorvastatin or rosuvastatin), with the potential to lower low-density lipoprotein cholesterol (LDL-C) levels.⁹ It is well known that combination therapies reduce the pill burden for patients, potentially enhancing treatment adherence and facilitating treatment with a goal of improving cardiovascular outcomes.^9,10

“As bempedoic acid and ezetimibe are already approved as a single-dose therapy, the development of an oral triple combination tablet with different doses of a statin, can make it easier for physicians to tailor treatment to the individual needs of each patient,” says Dr. Stefan Seyfried, Vice President and Head Medical Affairs Specialty Medicines, Daiichi Sankyo Europe. “This approach exemplifies our dedication to our motto: ‘we care for every heartbeat’.”

“The management of dyslipidaemias is undergoing the same evolution we previously witnessed in hypertension management. First, we learned to combine medication to achieve higher efficacy with fewer side effects, then we ascertained that replacing multiple separate pills with fixed-dose combination options increased adherence and improved outcomes,” says Prof. Yvonne Winhofer-Stöckl, Medical University of Vienna, Austria.

The announcement of the development of the oral triple combination coincides with the presentation at European Society of Cardiology (ESC) Congress 2025 of new clinical data from the MILOS and SANTORINI registries, which continue to emphasise ongoing challenges in LDL-C management.^1,2

• Data from four-country cohort of the MILOS study reveal that patients’ real cardiovascular (CV) risk is often underestimated in clinical practice, with up to 50% of high-risk patients and up to 70% of very high-risk patients assigned a lower CV risk and highlight treatment disparities between genders, with women less likely to receive intensive lipid-lowering therapy (LLT) than men.^3,6 Furthermore, the addition of bempedoic acid over eight weeks, with or without other LLTs, was associated with a reduction in LDL-C levels in both sexes with no new safety signals, supporting the real-world effectiveness and safety of bempedoic acid in both sexes.⁶
• SANTORINI data also expose gaps in LLT intensification, with only 20% of high-risk and very-high-risk patients with elevated LDL-C receiving treatment intensification, and older patients less likely to be treated intensively than younger patients.^4,5

In addition, real-world prescribing data show that nearly ¾ of high or very high CV risk patients in Germany are not prescribed any LLT.¹¹

The SANTORINI cohort of high-risk and very high-risk patients was also used in a simulation suggesting that 6 in 10 patients could achieve LDL-C goals and meaningfully reduce their long-term CV risk with an optimised triple oral LLT pathway (bempedoic acid, ezetimibe and a statin), in line with results presented at European Atherosclerosis Society (EAS) Congress 2025 showing that intensification with combination therapies resulted in better control of LDL-C levels than statin up titration.^7,12 The lipid-lowering potential of the oral triple combination is recognised in the latest 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias.⁸

CVD continues to pose a significant global challenge, and is the leading cause of death in Europe.¹³ Dyslipidaemia, or elevated LDL-C levels, is one of the most prevalent modifiable risk factors contributing to CV events, and its management remains a critical need in CV risk reduction.^14-16 Lipid-lowering therapies have been shown to reduce the risk of major adverse cardiovascular events (MACE).^14,15 However, despite the protective CV effects of these treatments, their use is often suboptimal due to inconsistent clinical practices, insufficient adherence (partly due to polypharmacy), treatment inertia and underutilisation of combination therapies, resulting in a substantial proportion of patients not reaching their recommended levels of LDL-C and remaining at high CV risk.^10,15,16

The Specialty Medicines Unit of Daiichi Sankyo intends to protect people from CVD and support those affected, helping them enjoy every precious moment of life. Daiichi Sankyo Europe is dedicated to identifying and addressing challenges in cardiovascular disease. We use a patient-centric approach to develop new solutions that have the potential to improve long-term health outcomes.

About SANTORINI

The SANTORINI (NCT04271280) study is a multinational, prospective, observational study that enrolled 9,602 patients with high and very high cardiovascular (CV) risk from over 623 sites in 14 countries across Europe. Patients were recruited between March 2020 and February 2021.^2,16 The primary objective was to document, in the real-world setting, the effectiveness of current low-density lipoprotein cholesterol (LDL-C) management approaches in high- and very high-cardiovascular risk patients requiring lipid-lowering therapies (LLT) over a 1-year period.¹⁷ The study included both previously diagnosed and treated patients and those newly diagnosed and requiring treatment.¹⁶ Complete baseline data was included for 9,044 patients (mean age: 65.3 ± 10.9 years; 72.6% male).¹⁶ Physicians used 2019 ESC/EAS guidelines as a basis for CV risk classification in 52% of patients; 29.2% of patients were classified as high risk and 70.8% as very high risk.¹⁶ Central reassessment with the same guidelines classified 6.5% as high risk and 91% as very high-risk.¹⁶ Overall, 21.8% of patients had no documented LLTs, 54.2% were receiving monotherapy and 24% combination LLT.¹⁶ Median LDL-C was 2.1 mmol/L with 20.1% of patients achieving risk based LDL-C goals as per the 2019 ESC/EAS guidelines.¹⁶

About MILOS

MILOS (NCT04579367) is an ongoing, multinational, European observational study in adult patients diagnosed with primary hypercholesterolaemia or mixed dyslipidaemia.¹ The aim is to evaluate the real-world use of bempedoic acid and bempedoic plus ezetimibe fixed-dose combination. Beyond Germany, MILOS has sites in Austria, Belgium, Italy, the Netherlands, Spain, Switzerland and the UK.¹

About Bempedoic Acid and its Fixed-Dose Combination with Ezetimibe

Bempedoic acid (NILEMDO®) is a first-in-class, oral, once-daily treatment that lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting ATP citrate lyase (ACL), upstream of the statin target in the cholesterol synthesis pathway.^18,19 It is not activated in skeletal muscle and can be used alone or in combination with statins or other lipid-lowering therapies, particularly in patients who are statin-intolerant or not achieving LDL-C goals. The fixed-dose combination of bempedoic acid and ezetimibe (NUSTENDI®) combines two different ways of reducing cholesterol in a once-daily tablet.²⁰

For full prescribing information, including indications and usage, refer to the respective Summary of Product Characteristics (SmPC).^18,20 Daiichi Sankyo Europe holds exclusive commercialisation rights for NILEMDO® and NUSTENDI® in the EEA, UK, Turkey, and Switzerland under license from Esperion.

About Atorvastatin and Rosuvastatin

These medicines belong to a group of medication that lower low-density lipoprotein cholesterol to block HMG-CoA reductase enzyme in the liver and thus the production of cholesterol. They act in the same pathway as bempedoic acid, but at a different point.^21,22

About Daiichi Sankyo

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops, and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular, and other diseases facing significant therapeutic needs. For more information, please visit www.daiichisankyo.com.

References

1. Treatment with bempedoic acid and/​or its fixed-dose combination with ezetimibe in primary hypercholesterolemia or mixed dyslipidemia (MILOS). Available at: https://clinicaltrials.gov/study/NCT04579367. Last accessed July 2025.

2. Treatment of high and very high risk dyslipidemic patients for the prevention of cardiovascular events (SANTORINI). Available at: https://clinicaltrials.gov/study/NCT04271280. Last accessed July 2025.

3. Parhofer KG, et al. Underestimation of cardiovascular risk in four European countries: results from the prospective, noninterventional MILOS. Presented at European Society of Cardiology (ESC) Congress 2025.

4. Aguiar C, et al. Predictors of lipid-lowering therapy intensification over 1 year of prospective follow-up in Europe: insights from the SANTORINI study. Presented at European Society of Cardiology (ESC) Congress 2025.

5. Connolly DL, et al. Age-stratified analysis of real-world lipid-lowering therapy use and LDL-C goal attainment at 1-year follow-up: insights from the European SANTORINI study. Presented at European Society of Cardiology (ESC) Congress 2025.

6. Gouni-Berthold I, et al. Undertreatment of women with lipid-lowering therapies in four European countries: results from the prospective, non-interventional MILOS Study. Presented at European Society of Cardiology (ESC) Congress 2025.

7. Katzmann JL, et al. Triple oral lipid-lowering treatment pathway and associated outcomes in high- and very high-CV risk patients: a simulation using the SANTORINI study cohort. Presented at European Society of Cardiology (ESC) Congress 2025.

8. Mach F, et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Developed by the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2025;ehaf190. doi:10.1093/eurheartj/ehaf190

9. Rubino J, et al. Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: A randomized clinical trial. Atherosclerosis. 2021;320:122–8.

10. Weisser B, et al. Effect of a single pill concept on clinical and pharmacoeconomic outcomes in cardiovascular diseases. Eur Heart J Cardiovasc Pharmacother. 2025;10(8):686–93.

11. Weingaertner O, et al. Real-world prescribing patterns for lipid-lowering therapy in high cardiovascular risk patients in Germany: a cross-sectional analysis. Presented at European Society of Cardiology (ESC) Congress 2025.

12. Connolly DL, et al. Initiating combination therapy facilitates better LDL-C goal attainment than statin up-titration over 1 year: an analysis from the SANTORINI study. Presented at European Atherosclerosis Society (EAS) Congress 2025.

13. World Health Organisation. Cardiovascular diseases. Available at: https://www.who.int/europe/news-room/fact-sheets/item/cardiovascular-diseases. Last accessed July 2025.

14. Nissen SE, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023. 13;388(15):1353-1364.

15. Mach F, et al. 2019 ESC/EAS Guidelines for the Management of dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. European Heart Journal. 2019 Aug 31;41(1).

16. Ray KK, et al. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study. The Lancet Reg Health Eur. 2023 Jun 1;29:100624.

17. Gouni-Berthold I, et al. Real-world effectiveness and safety of bempedoic acid in Europe: final 2-year results from the MILOS German cohort. Presented at DGK Hertztage 2024.

18. European Medicines Agency. Nilemdo – summary of product characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/product-information/nilemdo-epar-product-information_en.pdf. Last accessed July 2025.

19. Pinkosky SL, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016. 7: 13457.

20. European Medicines Agency. Nustendi – summary of product characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/product-information/nustendi-epar-product-information_en.pdf. Last accessed July 2025.

21. European Medicines Agency. Atorvastatin – summary of product characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/referral/sortis-article-6-12-referral-annex-i-ii-iii_en.pdf. Last accessed July 2025.

22. European Medicines Agency. Rosuvastatin –summary of product characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/referral/crestor-5-mg-article-29-referral-annex-i-ii-iii_en.pdf. Last accessed July 2025.

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