Daiichi Sankyo launches development of oral triple combination tablets for LDL cholesterol management in Europe

Daiichi Sankyo Europe has announced the start of development for a new oral triple combination therapy designed to address one of cardiology’s most persistent challenges: helping patients achieve and sustain recommended low-density lipoprotein cholesterol (LDL-C) targets. The initiative, unveiled alongside new real-world evidence at the European Society of Cardiology (ESC) Congress 2025 in Munich, combines bempedoic acid, ezetimibe, and varying doses of statins (atorvastatin or rosuvastatin) into a single pill.

The company said the aim is twofold—enhance LDL-C reduction efficacy and improve long-term adherence by reducing the pill burden faced by patients with cardiovascular disease (CVD). The development comes at a time when European registries such as MILOS and SANTORINI continue to highlight critical treatment gaps in lipid management, despite decades of innovation in statins and adjunct therapies.

Why is Daiichi Sankyo targeting LDL cholesterol with a triple combination oral therapy in 2025?

Cardiovascular disease remains the leading cause of death across Europe, accounting for millions of lives lost annually and exerting enormous strain on healthcare systems. Elevated LDL cholesterol is widely recognized as one of the most modifiable risk factors for heart attack, stroke, and other major adverse cardiovascular events (MACE). While statins have been the standard of care since the late 1980s, real-world evidence consistently shows that a significant proportion of high-risk and very high-risk patients fail to reach target LDL-C levels, even when prescribed high-intensity statin regimens.

This gap is not due solely to drug efficacy. Patient adherence remains a chronic challenge in lipid management. Many patients struggle with polypharmacy—taking multiple pills daily for cholesterol, blood pressure, diabetes, and other conditions. Fixed-dose combination therapies have proven in hypertension to increase compliance and improve outcomes by consolidating multiple agents into a single pill. According to data presented at ESC 2025, Daiichi Sankyo believes the same principle can now be applied to cholesterol management through a once-daily triple therapy that simplifies treatment and maximizes efficacy.

By integrating bempedoic acid, a relatively new ATP citrate lyase (ACL) inhibitor that works upstream of statins in the cholesterol biosynthesis pathway, with ezetimibe, a cholesterol absorption inhibitor, and a widely prescribed statin such as atorvastatin or rosuvastatin, the company is betting on a multipronged approach that could close existing gaps in LDL-C control. The strategic timing aligns with the 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias, which explicitly recognize the role of combination therapies in achieving ambitious LDL-C goals for high-risk patients.

What did the latest ESC 2025 data reveal about cardiovascular risk and lipid-lowering therapy?

The MILOS registry, which spans multiple European countries, presented fresh insights at ESC 2025. Researchers noted that in real-world practice, up to 50% of high-risk patients and 70% of very high-risk patients were systematically underestimated in terms of their actual cardiovascular risk. This misclassification led to significant treatment gaps, where patients at the highest risk were often not prescribed adequate lipid-lowering therapy (LLT).

In particular, the data exposed gender disparities. Women were less likely than men to receive intensive statin therapy, leaving them disproportionately exposed to adverse cardiovascular outcomes. The registry also examined outcomes with bempedoic acid and found that its use over an eight-week period, whether alone or combined with other LLTs, significantly reduced LDL-C across both male and female patient groups without revealing any new safety concerns. This real-world confirmation of bempedoic acid’s efficacy adds weight to its inclusion in combination therapy strategies.

Meanwhile, the SANTORINI registry, which focused on high-risk and very high-risk patients with established CVD across Europe, highlighted another issue: only 20% of patients with elevated LDL-C received treatment intensification when their cholesterol remained above recommended thresholds. Older patients were particularly under-treated compared to younger ones, underscoring the need for more flexible, patient-friendly treatment regimens.

A simulation study using SANTORINI data suggested that an optimized oral triple combination therapy—incorporating bempedoic acid, ezetimibe, and a statin—could enable nearly six in ten patients to achieve LDL-C targets. Analysts at ESC noted that this figure significantly outperformed outcomes typically observed when clinicians simply increase statin dosages, reinforcing the case for fixed-dose combinations.

How does Daiichi Sankyo’s strategy align with global cardiovascular disease management trends?

The concept of fixed-dose combination pills is not new. In hypertension, the introduction of single-pill combinations—pairing agents like ACE inhibitors with diuretics or calcium channel blockers—was a turning point in improving adherence and lowering overall cardiovascular events. In the same way, experts suggest that lipid-lowering could benefit from a similar paradigm shift.

Industry observers pointed out that Daiichi Sankyo has been steadily expanding its cardiovascular franchise beyond its well-established oncology pipeline. The company already markets bempedoic acid (as part of its collaboration with Esperion Therapeutics, NASDAQ: ESPR), and the move to combine it with ezetimibe and statins is a logical extension that leverages both innovation and familiarity. Analysts highlighted that oral delivery is particularly important in Europe, where injectable PCSK9 inhibitors such as Amgen’s (NASDAQ: AMGN) Repatha and Sanofi (EPA: SAN) / Regeneron Pharmaceuticals’ (NASDAQ: REGN) Praluent have gained traction but still face adherence and cost hurdles.

The new initiative also reflects broader European policy priorities. The European Society of Cardiology and the European Atherosclerosis Society (EAS) have been pushing for more aggressive LDL-C targets, arguing that “lower is better” when it comes to bad cholesterol. With cardiovascular disease accounting for more than 3.9 million deaths annually in Europe, the economic and societal case for stronger interventions is compelling.

What could the impact be on patients, physicians, and health systems?

If successful, Daiichi Sankyo’s oral triple combination tablets could provide patients with a more convenient and potentially more effective pathway to cholesterol management. By reducing the number of pills taken daily, the therapy could directly address the issue of treatment adherence—often cited as a critical barrier to long-term cardiovascular risk reduction.

For physicians, the availability of a customizable triple therapy (with different statin doses) may allow for more tailored treatment strategies. Cardiologists often face a balancing act between efficacy and tolerability; some patients are statin-intolerant or experience muscle-related side effects. The inclusion of bempedoic acid, which acts in the liver rather than muscles, may mitigate some of these issues and provide a tolerable alternative for patients unable to sustain high-dose statins.

At a system level, the potential for improved LDL-C target achievement could translate into fewer cardiovascular events, lower hospitalization rates, and reduced long-term costs for health services across Europe. This is particularly significant as aging populations increase the burden of heart disease, diabetes, and metabolic syndrome on national healthcare budgets.

How are investors and the pharmaceutical sector likely to respond to this development?

As a publicly traded company listed on the Tokyo Stock Exchange (TYO: 4568), Daiichi Sankyo’s strategy has drawn attention from investors monitoring the company’s dual focus on oncology and cardiovascular disease. Daiichi Sankyo’s recent financial results showed solid revenue contributions from its oncology partnerships, particularly with AstraZeneca (LON: AZN / NASDAQ: AZN) on Enhertu and Datopotamab deruxtecan. However, diversifying into cardiovascular therapy through innovative lipid-lowering approaches could help the company capture a significant portion of a market that global analysts value at over $30 billion annually, driven by rising statin use and the expansion of PCSK9 inhibitors.

Investor sentiment has been cautiously optimistic. Daiichi Sankyo’s stock has traded steadily in 2025, with moderate gains supported by strong oncology growth and expectations of future cardiovascular revenue streams. Market watchers suggest that if the triple combination shows favorable clinical trial results, Daiichi Sankyo could strengthen its competitive position against larger multinational players like Novartis (SWX: NOVN) and Pfizer (NYSE: PFE), both of which maintain active lipid-lowering pipelines.

Institutional flows into Japanese pharmaceutical equities have been selective in recent months, with global funds focusing more heavily on oncology and immunology names. However, given the persistent unmet need in LDL-C management, Daiichi Sankyo’s announcement may catalyze renewed attention on cardiovascular innovation. Analysts have hinted that the triple therapy program could become a medium-term growth driver, potentially offsetting pricing pressures in Japan’s domestic market and helping the company solidify its global presence.

What are the broader implications for the future of cardiovascular treatment?

The initiation of this oral triple combination program underscores a major trend in cardiovascular care: the recognition that monotherapy is often insufficient for high-risk patients. Just as the hypertension field moved decisively toward combination therapy decades ago, lipid-lowering medicine may be on the verge of a similar transformation.

Real-world evidence from MILOS and SANTORINI shows that traditional statin-centric approaches are not achieving sufficient results. By combining complementary mechanisms of action into a single pill, Daiichi Sankyo is positioning itself at the intersection of convenience, adherence, and efficacy—a combination that could prove decisive in the battle against CVD.

While regulatory approval and real-world outcomes will ultimately determine the success of the initiative, the company’s decision to embark on this path reflects a broader pharmaceutical industry push toward fixed-dose combinations, patient-centric design, and real-world validation. For healthcare systems grappling with the economic toll of cardiovascular disease, therapies that improve adherence and outcomes without significantly raising costs could be game-changers.

As the industry awaits further clinical trial data in the coming years, Daiichi Sankyo’s move has already signaled that the race to reshape LDL cholesterol management is intensifying. If the program delivers on its promise, it may set a new benchmark for how cardiovascular risk is treated in Europe and beyond, much like combination therapy reshaped hypertension care a generation ago.