Daiichi Sankyo Europe has announced the initiation of development for new oral triple combination tablets containing bempedoic acid, ezetimibe, and different doses of statins (atorvastatin or rosuvastatin) aimed at improving low-density lipoprotein cholesterol (LDL-C) management and treatment adherence. The announcement coincides with new clinical data from the MILOS and SANTORINI registries presented at the European Society of Cardiology (ESC) Congress 2025, which highlight persistent challenges in cardiovascular risk assessment and LDL-C target achievement.
Addressing Critical Treatment Gaps
Recent findings from the four-country MILOS study cohort reveal significant gaps in cardiovascular risk assessment, with up to 50% of high-risk patients and up to 70% of very high-risk patients having their cardiovascular risk underestimated in clinical practice. The data also expose treatment disparities between genders, with women less likely to receive intensive lipid-lowering therapy than men.
The SANTORINI registry data further emphasize treatment inadequacies, showing that only 20% of high-risk and very high-risk patients with elevated LDL-C receive treatment intensification. Additionally, older patients are less likely to be treated intensively than younger patients. Real-world prescribing data from Germany reveal that nearly three-quarters of high or very high cardiovascular risk patients are not prescribed any lipid-lowering therapy.
Triple Combination Potential
Simulation analysis using the SANTORINI cohort of high-risk and very high-risk patients suggests that 6 in 10 patients could achieve LDL-C goals and meaningfully reduce their long-term cardiovascular risk with an optimized triple oral lipid-lowering therapy pathway combining bempedoic acid, ezetimibe, and a statin. This finding aligns with results presented at the European Atherosclerosis Society (EAS) Congress 2025, which demonstrated that intensification with combination therapies resulted in better control of LDL-C levels than statin up-titration alone.
"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," said Dr. Stefan Seyfried, Vice President and Head Medical Affairs Specialty Medicines, Daiichi Sankyo Europe.
Clinical Evidence and Safety Profile
The MILOS study data demonstrate that the addition of bempedoic acid over eight weeks, with or without other lipid-lowering therapies, 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.
The SANTORINI study, a multinational, prospective, observational study, enrolled 9,602 patients with high and very high cardiovascular risk from over 623 sites in 14 countries across Europe. Complete baseline data was included for 9,044 patients (mean age: 65.3 ± 10.9 years; 72.6% male). The study revealed that only 20.1% of patients achieved risk-based LDL-C goals as per the 2019 ESC/EAS guidelines, with a median LDL-C of 2.1 mmol/L.
Regulatory Alignment and Clinical Need
The lipid-lowering potential of the oral triple combination is recognized in the latest 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Prof. Yvonne Winhofer-Stöckl from the Medical University of Vienna, Austria, noted that "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."
Cardiovascular disease continues to pose a significant global challenge and is the leading cause of death in Europe. Dyslipidaemia, or elevated LDL-C levels, is one of the most prevalent modifiable risk factors contributing to cardiovascular events. Despite the protective cardiovascular effects of lipid-lowering therapies, their use is often suboptimal due to inconsistent clinical practices, insufficient adherence (partly due to polypharmacy), treatment inertia, and underutilization of combination therapies.
Mechanism of Action
Bempedoic acid (NILEMDO®) is a first-in-class, oral, once-daily treatment that lowers LDL-C by inhibiting ATP citrate lyase (ACL), upstream of the statin target in the cholesterol synthesis pathway. 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 mechanisms of cholesterol reduction in a once-daily tablet.
The development of this triple combination tablet represents Daiichi Sankyo's commitment to addressing cardiovascular disease challenges through a patient-centric approach aimed at improving long-term health outcomes and treatment adherence.
