Daiichi Sankyo Europe GmbH

MUNICH--( BUSINESS WIRE )--For EU media only Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) today announced final 2-year follow-up data from the German cohort of the multinational, European observational MILOS study. 1 The study evaluated the real-world use of bempedoic acid, marketed as NILEMDO ® ▼ and its FDC with ezetimibe, NUSTENDI ® ▼, in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The results, presented in Hamburg, Germany at DGK Hertztage 2024, demonstrated the effectiveness and safety profile of bempedoic acid, both alone and in combination with other lipid-lowering therapies (LLTs) in clinical practice. 1 Raised LDL-C is a key modifiable contributor to risk of major cardiovascular events, with studies showing that every 1 mmol/L reduction in LDL-C is associated with a 22% reduction in major cardiovascular events after one year. 5,6 The German cohort of MILOS study comprising 973 patients from 125 sites in Germany, is one of the most comprehensive assessments of bempedoic acid in a real-world clinical setting to-date in Germany. 1 Patients were followed-up for two years, with LDL-C levels assessed at pre-treatment, one year (1Y) and two years (2Y). Overall, 638 of 973 patients (65.6%) completed 2Y follow up, with LDL-C values at pre-treatment, 1Y and 2Y available for 451 patients. In these 451 patients, a mean reduction of LDL-C levels from 3.1 mmol/L (121.4 mg/dL) at pre-treatment, to 2.0 mmol/L (77.2 mg/dL) was observed, representing an average relative reduction of 30.3% in the overall population. 1 Additionally, the percentage of patients reaching their LDL-C goals increased from 4.9% at pre-treatment to 35.3% at the 2Y follow-up – an approximately 7-fold increase. 1 The proportions of high-risk and very high-risk patients reaching LDL-C goals increased from 5.6% to 32.5%, and 3.6% to 35.2%, respectively. 1 Overall, more than 80% of patients received bempedoic acid in combination with other LLTs at pre-treatment and 2Y, including statins and ezetimibe. The safety profile of bempedoic acid in this real-world population was assessed at 1Y and 2Y and was consistent with that observed in the CLEAR clinical trial programme. 2,3,4 “By significantly lowering LDL-C levels toward guideline goals, we are taking a vital step in reducing the risk of cardiovascular events, which can have a profound impact on a person’s long-term health and quality of life,” said Professor Ioanna Gouni-Berthold, University of Cologne, Center for Endocrinology, Diabetes, and Preventive Medicine and Executive Board Member of the International Atherosclerosis Society . “Cardiovascular disease remains Europe’s leading cause of death, yet the majority of premature CV events are preventable,” 7,8 said Dr. Stefan Seyfried, Vice President Medical Affairs, Specialty Medicines, at Daiichi Sankyo Europe GmbH . “ The findings from this cohort reinforce the benefit provided by bempedoic acid for reducing LDL-C levels. Our long-term goal is to empower the medical community with real-world insights to improve CVD prevention and, ultimately, improve patient care.” -ENDS- About MILOS MILOS (NCT04579367) is an ongoing, multinational, European observational study in adult patients diagnosed with primary hypercholesterolaemia or mixed dyslipidaemia. The aim is to evaluate the real-world use of bempedoic acid and bempedoic plus ezetimibe FDC. Patients in the German cohort were recruited from 125 sites between January 2021 and January 2022 and were followed up for 2 years after baseline measurements. 1 Change in LDL-C levels and the proportion of patients achieving LDL-C goal were assessed in patients at pre-treatment, 1Y and 2Y visits. Analyses were stratified by investigator-assessed CV risk, based on the ESC/EAS dyslipidaemia guidelines. 1 Beyond Germany, MILOS has sites in Austria, Belgium, Italy, the Netherlands, Spain, Switzerland and the UK. 9 About Bempedoic Acid and its Fixed-Dose Combination with Ezetimibe Bempedoic acid (NILEMDO ® ) is a first-in-class, oral, once-daily treatment to lower cholesterol, and can be combined with other oral treatments to help lower cholesterol even further. 10 Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme which is involved in the production of cholesterol in the liver. 10 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 LDL-C-lowering therapies. 11 Bempedoic acid is not activated in skeletal muscle. 10 Bempedoic acid is indicated in adults with primary hypercholesterolaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia, as an adjunct to diet: 10 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, 10 alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated. 10 Bempedoic acid is indicated in adults with established or at high risk for atherosclerotic CV disease to reduce CV risk by lowering LDL-C levels, as an adjunct to correction of other risk factors: 10 in patients on a maximum tolerated dose of statin with or without ezetimibe or, 10 alone or in combination with ezetimibe in patients who are statin-intolerant, or for whom a statin in contraindicated. 10 The bempedoic acid / ezetimibe FDC (NUSTENDI ® ) combines two complementary ways of reducing cholesterol in a once-daily tablet. Bempedoic acid / ezetimibe FDC is indicated in adults with primary hypercholesterolaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia, as an adjunct to diet: 12 in combination with a statin in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin in addition to ezetimibe, 12 alone in patients who are either statin-intolerant or for whom a statin is contraindicated, and are unable to reach LDL-C goals with ezetimibe alone, 12 in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin. 12 Bempedoic acid / ezetimibe FDC is indicated in adults with established or at high risk for atherosclerotic CV disease to reduce CV risk by lowering LDL-C levels, as an adjunct to correction of other risk factors: 12 in patients on a maximum tolerated dose of statin and not adequately controlled with additional ezetimibe treatment or, 12 in patients who are either statin-intolerant, or for whom a statin in contraindicated, and not adequately controlled with ezetimibe treatment or, 12 in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets. 12 Daiichi Sankyo Europe has licensed exclusive commercialisation rights to bempedoic acid and its FDC with ezetimibe (marketed as NILEMDO ® and NUSTENDI ® ) in the European Economic Area, UK, Turkey and Switzerland from Esperion and is the full Marketing Authorisation Holder in these territories. 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 with high unmet medical need. For more information, please visit https://www.daiichi-sankyo.eu/ ▼ This medicinal product is subject to additional monitoring. References 1 DGK Hertztage 2024 Abstract. Real-world effectiveness and safety of bempedoic acid in Europe: final 2-year results from the MILOS German cohort. Gouni-Berthold, I et al. 2 Nissen SE, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med . 2023;388:1353–64 3 Ray KK, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med . 2019; 380:1022–32 4 Ballantyne CM, et al . Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol . 2020; 27(6): 593–603 5 Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010. 376(9753): 1670–1681 6 NHS England. Improving lipid management to reduce cardiovascular disease and save lives. Available at: https://www.england.nhs.uk/long-read/improving-lipid-management-to-reduce-cardiovascular-disease-and-save-lives/#:~:text=Raised%20LDL%20cholesterol%20is%20one,vascular%20events%20after%201%20year . Last accessed September 2024. 7 Eurostat. (2023) Causes of death statistics. Available at: https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Causes_of_death_statistics#Major_causes_of_death_in_the_EU_in_2020 . Last accessed September 2024. 8 World Heart Federation. Prevention. Available at: https://world-heart-federation.org/what-we-do/prevention/#:~:text=An%20estimated%2080%25%20of%20cardiovascular,and%20“knowing%20your%20numbers ”. Last accessed September 2024 9 ClinicalTrials.gov. 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#contacts-and-locations . Last accessed September 2024. 10 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 September 2024. 11 Pinkosky, S.L., et al . Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun . 2016. 7: 13457. 12 European Medicines Agency. Nustendi –Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/nustendi-epar-product-information_en.pdf . Last accessed September 2024 HQ/BIL/09/24/0001

MUNICH--( BUSINESS WIRE )--Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) today announced its reinforced commitment to addressing key unmet needs and barriers in cardiovascular (CV) care, by shining a light on inequalities in treatment and outcomes experienced by various patient groups. The announcement follows the presentation of data from sub-analyses of the SANTORINI observational study and ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) study programme, at the European Society of Cardiology (ESC) Congress 2024. Gender inequalities in CV disease treatment and LDL-C goal attainment Raised low-density lipoprotein cholesterol (LDL-C) is a key modifiable contributor to risk of cardiovascular major events. It has been shown that for every 1 mmol/L reduction in LDL-C, there is a 22% reduction in major cardiovascular events after 1 year. 7,8 Female patients in Europe who are at high or very high CV risk were undertreated and less achieved guideline-recommended LDL-C levels, according to data from the observational SANTORINI study. 1 As part of its efforts to expand medical knowledge to help protect people from CV disease (CVD), Daiichi Sankyo funds and designs studies, such as SANTORINI, that investigate the underlying causes behind the burden of CVD in Europe. Data from a new sub-analysis of SANTORINI, based on 5,197 male patients with a mean age of 65 years, and 2,013 females with a mean age of 66 years, showed that female patients were undertreated compared to men as fewer achieved guideline-recommended LDL-C levels within the study. 1 While the proportion of patients reaching LDL-C goals improved from baseline to 1-year follow up, it was greater in males (22.9% and 33.3%, respectively) than in females (16.9% and 24.6%,). 1 Despite similar guideline recommendations, more females received no lipid-lowering therapies at baseline and 1-year follow up (23.9% to 3.9%, respectively) than males (20.7% to 2.7%). 1 “We know that the severity of cardiovascular disease for women is as high as it is with men, and patients of both sexes remain undertreated. 9,10 But this new sub-analysis of the SANTORINI study further suggests that in clinical practice, women as a group were being disproportionally undertreated and do not always reach recommended LDL-C level goals,” said Professor David Nanchen, University of Lausanne, Center for Primary Care and Public Health (Unisanté), Lausanne, Switzerland. “These findings underscore the need for more widespread attention to better manage the risk of cardiovascular disease in women. ” Treatment adherence and the impact of non-adherence on patient outcomes Treatment for atrial fibrillation with oral anticoagulation relies on adherence and persistence to be effective. Non-persistence to single non-vitamin K antagonist oral anticoagulants (NOACs) has been associated with increased stroke risk in atrial fibrillation (AF) patients. 2 Daiichi Sankyo committed to ETNA-AF, which combines data from distinct non-interventional studies in Europe, East Asia, and Japan in a single database, to delve deeper into the global burden of CVD. More than 28,000 patients were included in the ETNA-AF registries and followed for four years in Europe and two years in countries outside Europe. 11 Results from a new post hoc sub-analysis of the ETNA-AF programme showed that, of the 9,417 [13,164 enrolled] (71.5%) patients who completed the 4-year study, 87.4% were persistent with edoxaban treatment. 3 Treatment discontinuation and non-persistence were both associated with factors including increasing age, male sex, body weight extremes, low renal function, heart failure, vascular disease, chronic hepatic disease, alcohol use, perceived frailty, chronic obstructive pulmonary disease, smoking, current AF symptoms, and ablation. 3 “The high number of patients who persisted with edoxaban treatment for the duration of the 4-year study is good news for our efforts to mitigate therapeutic non-adherence, 2 ” said Professor Raffaele De Caterina, MD, PhD, FESC, Director of Cardiology at Pisa University Hospital. “ We hope that the associated factors for non-persistence observed in the study will also assist the development of treatment strategies in clinical practice, for the benefit of patient outcomes.” Treatment for patients with frailty and comorbidities Barriers to recommending anticoagulation to manage non-valvular AF (NVAF), such as complex multimorbidities are significant in frail patients. 12 As such, the prescription of NOACs in the frail patient population is <50%. 12 Doctors are required to balance stroke risk and bleeding risk when making prescribing decisions. 12 Frailty is a common reason to choose non recommended doses of NOACs and so the four year follow up data from ETNA-AF were used to assess clinical outcomes in such patients. Patients with 'perceived' or objective frailty who were treated with a reduced (non-recommended) 30mg dose showed a higher rate of all-cause death versus the 60mg dose (HR [95% CI]: 1.44[1.06,1.96]) with no significant effect on major bleeding. This suggests that the presence of frailty per se should not necessarily drive dose reductions. 5 In a separate sub analysis of the data, patients were divided into low, middle and high tertiles based on body mass index (BMI), body surface area (BSA) and lean body mass (LBM). Rates of thromboembolic events were low (0.7-0.9%/100PY) and similar across tertiles. However, higher rates of any haemorrhagic events were observed in the low ([2.2–2.4%]) vs middle ([1.5–1.8%]) and high ([1.4–1.5%]) tertiles for BSA and LBM, suggesting that these variables, more than BMI, should be considered when analysing outcomes in patients treated with edoxaban. 4,6 “At Daiichi Sankyo, we continue in our long-term commitment to provide scientific evidence that can support the optimal treatment of patients with cardiovascular disease, and to find solutions for individuals who have previously been undertreated,” said Dr. Stefan Seyfried, Vice President Medical Affairs, Specialty Medicines, at Daiichi Sankyo Europe GmbH. “ Our promise to patients is to continue shining a light on treatment inequalities and unmet needs in cardiovascular care, with the goal of reducing the burden on patients and their loved ones. ” -ENDS- About SANTORINI The SANTORINI study is a multinational, prospective, observational study that enrolled 9,602 patients with high and very high CV risk from over 623 sites in 14 countries across Europe. Patients were recruited between March 2020 and February 2021. 10 The primary objective was to document, in the real-world setting, the effectiveness of current LDL-C management approaches in high- and very high-cardiovascular-risk patients requiring lipid-lowering therapies over a 1-year period. 10 The study included both previously diagnosed and treated patients and those newly diagnosed and requiring treatment. 10 Complete baseline data was included for 9,044 patients (mean age: 65.3 ± 10.9 years; 72.6% male). 10 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. 10 Central reassessment with the same guidelines classified 6.5% as high risk and 91% as very high-risk. 10 Overall, 21.8% of patients had no documented lipid lowering therapies (LLTs), 54.2% were receiving monotherapy and 24% combination LLT. 10 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. 10 About ETNA-AF ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) is a global programme that combines data from distinct non-interventional studies in Europe, East Asia, and Japan in a single database. A total of more than 28,000 patients were included in the ETNA-AF registries and followed for two years (patients in Europe were followed for four years). 11 The primary objective of ETNA-AF was to collect information on the use of edoxaban in routine clinical practice, including the safety and efficacy profile in non-preselected patients with nonvalvular AF. 13,14,15,16,17 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 with high unmet medical need. For more information, please visit https://www.daiichi-sankyo.eu/ References ________________________________ 1 Nanchen, D., et al. Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study. Oral presentation, ESC Congress 30 August 2024. 2 Vitolo, M., et al. The importance of adherence and persistence with oral anticoagulation treatment in patients with atrial fibrillation. European Heart Journal – Cardiovascular Pharmacotherapy. 2021. 7;(FI1): f81–f83 3 Diemberger, I., et al . Persistence and predictors for non-persistence to edoxaban therapy in patients with atrial fibrillation: 4-year follow-up data from the ETNA-AF-Europe study. ESC Congress 2024 4 Boriani, G., et al . Impact of differences in body mass index, body surface area and lean body mass on clinical outcomes in patients with atrial fibrillation receiving edoxaban: 4-year follow-up data from ETNA-AF-Europe. ESC 2024 5 Fumagalli, S., et al . Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up. ESC 2024 6 Boriani, G., et al . Impact of body weight and body mass index on clinical outcomes of edoxaban therapy in atrial fibrillation patients included in the ETNA-AF-Global registry. ESC 2024 7 Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010. 376(9753): 1670–1681 8 NHS England. Improving lipid management to reduce cardiovascular disease and save lives. Available at: https://www.england.nhs.uk/long-read/improving-lipid-management-to-reduce-cardiovascular-disease-and-save-lives/#:~:text=Raised%20LDL%20cholesterol%20is%20one,vascular%20events%20after%201%20year . Last accessed August 2024. 9 ESC. Cardiovascular Disease in Women. Available at: https://www.escardio.org/The-ESC/Advocacy/women-and-cardiovascular-disease . Last accessed August 2024. 10 Ray, K.K., 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. Lancet . 2023. 29: 100624. 11 Daiichi Sankyo Europe – ETNA-AF (UK). Available at: https://www.daiichi-sankyo.eu/media/about-etna-af-uk/ . Last accessed August 2024. 12 Bul, M., et al. Frailty and oral anticoagulant prescription in adults with atrial fibrillation: A systematic review. Aging Medicine. 2022. 6(2): 195–206 13 Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-EU). Available at: https://clinicaltrials.gov/ct2/show/NCT02944019 . Last accessed August 2024. 14 Edoxaban Treatment in Routine Clinical Practice for Patients With Atrial Fibrillation in Korea and Taiwan (ETNA-AF-KOR-TWN). Available at: https://clinicaltrials.gov/ct2/show/NCT02951039 . Last accessed August 2024. 15 Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF-Hong Kong). Available at: https://clinicaltrials.gov/ct2/show/NCT03247582 . Last accessed August 2024. 16 Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (NVAF). Available at: https://clinicaltrials.gov/ct2/show/NCT03247569 . Last accessed August 2024. 17 ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000019728 . Last accessed August 2024.

Pictured: Brown gavel on a wooden table, with a book in the background/iStock, nathaphat Daiichi Sankyo and Esperion Therapeutics have reached an “amicable” resolution toa legal battle over milestone payments related to their cardiovascular drug collaboration. Under a settlement announced on Wednesday, Daiichi has agreed to pay Esperion $125 million in two separate tranches. Daiichi will pay Esperion $100 million in the middle this month ahead of a Type II variation approval by the European Medicines Agency for the cholesterol medications Nilemdo and Nustendi. In addition, Daiichi will make a $25 million payment to Esperion sometime in the quarter following the EMA’s decision. The resolution between the two companies will also see Esperion have Daiichi Sankyo Europe handle all production and supply operations in the European Union and for other territories. Under the agreement, Daiichi will lead all regulatory communications with the EMA. Both companies also plan to expand the collaboration in Europe and elsewhere to include the development and eventual commercialization of a “triple formulation product,” which consists of bempedoic acid, ezetimibe and a statin. Wednesday’s agreement resolves a dispute between the companies that boiled over in early 2023. At the time, Daiichi did not trigger a milestone payment to Esperion after Phase III trials for Nexletol (bempedoic acid) were presented, showing that the drug had reduced major adverse cardiovascular events by 13% while reducing heart attack risk by 23% and coronary revascularization by 19%. While Esperion felt that the results necessitated some form of payment, Daiichi thought otherwise which led to a spat in payment in the courts being filed in March 2023. As a result of the companies’ resolution to their commercial dispute, all further legal actions have been dismissed in the U.S. District Court for the Southern District of New York, according to Wednesday’s announcement. “We are pleased that this settlement creates value for Esperion today through cash payments and includes additional terms that will continue creating value for both companies going forward. Importantly, today’s settlement allows Esperion and DSE to focus on the business at hand – delivering life-saving drug therapies to millions with high cholesterol,” Esperion CEO Sheldon Koenig said in a statement. “This is a positive resolution for patients. We look forward to continuing to apply our combined strengths around the world to bring innovative pharmaceutical products to patients with cardiovascular disease, the greatest cause of death and disability globally,” Oliver Appelhans, head of Daiichi Sankyo Europe’s specialty business unit, said in a statement. Another one of Daiichi Sankyo’s subsidiaries, Plexxikon, reached a $182 million settlement with Novartis in December 2023 over the sale of the cancer drug Tafinlar. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.