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




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.

MUNICH, Germany–(BUSINESS WIRE)–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.

Contacts

Media Contact
Shreya Pandey

Daiichi Sankyo Europe GmbH

Senior Public Relations Manager

+49 151 5519 4223

Daiichi Sankyo Announces the Development of a Fixed-Triple Combination Lipid-Lowering Tablet to Address Persistent Gaps in the Management of Elevated LDL-C




Daiichi Sankyo Announces the Development of a Fixed-Triple Combination Lipid-Lowering Tablet to Address Persistent Gaps in the Management of Elevated LDL-C

MUNICH, Germany–(BUSINESS WIRE)–Daiichi Sankyo Europe is pleased to announce the development of a fixed-triple oral combination lipid-lowering tablet of bempedoic acid, ezetimibe, and different doses of a statin, with the potential to lower low-density lipoprotein cholesterol (LDL-C) levels.^{i ii}

“As bempedoic acid and ezetimibe are already approved as a single-dose therapy, the development of an oral triple combination with different doses of a statin, will 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’”.

Daiichi Sankyo is prioritising the development programme further to ongoing data readouts from their funded MILOS and SANTORINI registries which continue to emphasise the persistent gaps in LDL-C management and the health inequalities this exacerbates.

Professor of Public Health and Honorary Cardiologist at Imperial College London, Professor Kausik Ray added, “Heart disease remains the leading cause of death in Europe despite the significant strides forward we have taken in recent years; improvements in part enabled by more effective cholesterol management. However, data from the MILOS and SANTORINI registries exposes the ongoing inconsistencies in LDL-C management, in particular the disparities with worse LDL-C control and lower uses of evidence based therapies in women. I welcome further research that continues to explore ways that we can close these gaps and improve outcomes.”

Professor Raj Thakkar, President and CKD lead, Primary Care Cardiovascular Society, said, “The systematic and proactive population management of lipids is essential to reduce cardiovascular risk burden. To deliver this in an expedient, sustainable and efficient way is paramount. Ensuring all available therapies are used to minimise risk, including combination medicines, is key to delivering these goals.”

Notes to editors

The European Society of Cardiology (ESC) Congress takes place 29 August to 1 September 2025 in Madrid, Spain.

At ESC 2025 further clinical data from the SANTORINI and MILOS studies will be published, see about the trials below.

About SANTORINI

The SANTORINI study, funded by Daiichi Sankyo Europe, 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.^{iii iv} 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.^v

About MILOS

The MILOS study (NCT04579367), funded by Daiichi Sankyo Europe, 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.^vi

About Bempedoic Acid and its Fixed-Dose Combination with Ezetimibe

Concomitant use of bempedoic acid (NILEMDO^®)/bempedoic acid / ezetimibe FDC (NUSTENDI^®) with simvastatin > 40mg daily is contraindicated.

Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme which is involved in the production of cholesterol in the liver. Bempedoic acid is indicated in adults with primary hypercholesterolaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia, as an adjunct to diet:^vii

• 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,^viii
• alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.^ix

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:

• in patients on a maximum tolerated dose of statin with or without ezetimibe or, ^x
• alone or in combination with ezetimibe in patients who are statin-intolerant, or for whom a statin in contraindicated.^xi

The bempedoic acid / ezetimibe FDC is indicated in adults with primary hypercholesterolaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia, as an adjunct to diet:^xii

• 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,
• 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,
• in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin.^xiii

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:²¹

• in patients on a maximum tolerated dose of statin and not adequately controlled with additional ezetimibe treatment or,
• in patients who are either statin-intolerant, or for whom a statin in contraindicated, and not adequately controlled with ezetimibe treatment or,
• in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets.^xiv

Daiichi Sankyo Europe has licensed exclusive commercialisation rights to bempedoic acid and its FDC with ezetimibe 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 www.daiichi-sankyo.co.uk.

Contacts

James Hargrave

Director of Government Affairs

Daiichi Sankyo UK

James.Hargrave@daiichisankyo.com
+44 7591950136

Genentech and Alnylam Advance Zilebesiran Into Global Phase III Cardiovascular Outcomes Trial for People With Uncontrolled Hypertension




Genentech and Alnylam Advance Zilebesiran Into Global Phase III Cardiovascular Outcomes Trial for People With Uncontrolled Hypertension

–  Phase III trial informed by comprehensive KARDIA data set generated through three Phase II studies: KARDIA-1, KARDIA-2 and KARDIA-3 –

–  In the Phase II KARDIA-3 study, presented today as a late breaker at the European Society of Cardiology Congress 2025, zilebesiran demonstrated clinically meaningful reductions in office systolic blood pressure at month three with continuous control through month six –

– Zilebesiran, a potential best-in-disease RNAi antihypertensive with twice-yearly subcutaneous dosing, demonstrated encouraging safety when combined with two or more antihypertensives –

– Phase III cardiovascular outcomes trial expected to be initiated by the end of the year –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) and Alnylam (Nasdaq: ALNY) today announced the decision to initiate a Phase III cardiovascular outcomes trial (CVOT) to evaluate the ability of zilebesiran, an RNAi therapeutic, to reduce the risk of major adverse cardiovascular events in patients with uncontrolled hypertension. This decision was informed by the comprehensive KARDIA Phase II program, including KARDIA-1, KARDIA-2 and the most recent KARDIA-3 study evaluating the efficacy and safety of zilebesiran in patients with uncontrolled hypertension and high cardiovascular (CV) risk, on two to four standard of care antihypertensives. In particular, KARDIA-3 aimed to define the patient population to be investigated in the Phase III CV outcomes trial.

Results of KARDIA-3 showed a single dose of zilebesiran (300 mg every six months, subcutaneous injection) resulted in clinically meaningful placebo-adjusted reductions of office systolic blood pressure (SBP) in all comers at the month three primary endpoint (-5.0 mmHg; p=0.0431) with sustained benefits out to month six (-3.9 mmHg; 95% CI: [-8.5, 0.7]). There were no additional benefits of the 600 mg dose at month three (-3.3 mmHg; p=0.1830) or month six (-3.6 mmHg; 95% CI: [-8.2, 1.0]). The overall KARDIA-3 study did not meet the pre-specified definition for statistical significance, because of a multiplicity statistical testing approach. However the study met the aim of identifying the patient population that could potentially benefit the most from zilebesiran and also showed encouraging safety and clinically meaningful placebo adjusted reductions in blood pressure.

As observed in the KARDIA-2 Phase II study, the KARDIA-3 results support a robust benefit of combining zilebesiran with a diuretic, a commonly used antihypertensive. In an analysis of patients that were on diuretics and had a baseline BP > 140 mmHg, the placebo-adjusted reduction was -9.2 mmHg; (-17.3, -1.2) at month three and -8.3 mmHg (-16.4, -0.2) at month six. A precedent for enhanced blood pressure reduction conferred by this type of combination is established in both literature and clinical practice.

“Zilebesiran has the potential to become a best-in-disease treatment for many patients with uncontrolled hypertension. Its blood pressure-lowering effects and twice-yearly dosing could reduce the risk of serious health complications and death,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Detailed analysis of our comprehensive Phase II clinical trials have informed our decision to move zilebesiran into Phase III. Despite current treatment options, up to 80% of people with hypertension do not achieve adequate blood pressure control putting them at higher risk of cardiovascular events. Therefore, additional treatment options are needed.”

Zilebesiran also demonstrated encouraging safety in patients with comorbidities on multiple background therapies – over 90% of whom were receiving treatment with an ACE inhibitor or an Angiotensin Receptor Blocker (ARB). These findings reinforce confidence in zilebesiran’s ability to be combined with standard of care antihypertensives.

As a result, the global ZENITH (ZilebEsiraN cardIovascular ouTcome study in Hypertension) Phase III trial has been submitted to global regulators and is expected to be initiated by the end of 2025. ZENITH will be a CVOT enrolling approximately 11,000 patients and evaluating zilebesiran (300 mg) every six months compared to placebo in patients with uncontrolled hypertension with either established CV disease or at high risk for CV disease on two or more antihypertensives, one being a diuretic.

Hypertension is the primary cause of and number one modifiable risk factor for cardiovascular disease. An estimated one in three adults, over 1.2 billion people worldwide, have hypertension and despite the wide availability of antihypertensives, up to 80% of them do not achieve adequate blood pressure control. Poor adherence to daily oral therapies is an important contributor to poor blood pressure control and CV outcomes. An effective long-acting therapy that provides continuous control of blood pressure may help to reduce the burden of uncontrolled hypertension.

With its growing cardiometabolic portfolio and strong diagnostic expertise, Genentech is advancing transformative standards of care to improve the lives of people living with cardiometabolic diseases as well as reducing the significant burden on healthcare systems and society.

About the KARDIA-3 Study

KARDIA-3 (NCT06272487), the third Phase II study in the KARDIA program, included two Cohorts (A and B). Cohort A assessed zilebesiran in patients with eGFR ≥ 45 mL/min/1.73m2, while Cohort B included patients with advanced kidney dysfunction (i.e., eGFR between 30 and <45 mL/min/1.73m2). Cohort A enrolled 270 patients who were randomized to treatment with zilebesiran (300 mg or 600 mg) or placebo. Randomization was stratified by background diuretic use, baseline blood pressure, and race. The primary endpoint was change in office SBP at month three. Key secondary endpoints were changes in office SBP at month six and change in 24-hour mean ambulatory SBP at months three and six.

At baseline, 144 (53.3%), 96 (35.6%) and 30 (11.1%) patients were on two, three, or over three antihypertensives, respectively, with ~91% of patients taking ACE inhibitors/ARBs, ~66% of patients taking a diuretic, and ~58% of patients taking calcium channel blockers. The mean baseline office and 24-hour mean ambulatory SBP were 143.6 mmHg and 142.4 mmHg, respectively (N= 270).

KARDIA-3 Cohort A Primary Results (Placebo-Adjusted Changes from Baseline):

In summary, in the Cohort A overall study population, zilebesiran 300 mg achieved clinically meaningful reductions in office SBP at month three, with sustained benefits out to month six, compared to placebo. No incremental SBP reductions were observed with zilebesiran 600 mg at months three or six. Post-hoc analyses suggest that a greater blood pressure-lowering effect with zilebesiran was observed in patients on diuretic therapy and uncontrolled hypertension at baseline (with office SBP ≥140). Reductions in blood pressure were sustained over six months, and the entire 24-hour period. Incremental reductions were also observed at nighttime, a period during which blood pressure elevations is a strong predictor of cardiovascular risk.

Consistent with prior studies, zilebesiran demonstrated an encouraging safety profile when added to two or more background antihypertensives (over 90% of whom were receiving treatment with an ACE inhibitor or an ARB). Most adverse events were mild or moderate, non-serious, and transient with few requiring intervention; rates of hyperkalaemia, kidney dysfunction, and hypotension were low. Across study arms, serious adverse events were observed in 3.8% and 4.5% in zilebesiran and placebo-treated patients, respectively. No deaths were reported during the six-month double-blind period.

Results from KARDIA-3 Cohort B are expected to be presented at an upcoming medical meeting.

About the ZENITH CVOT

The global Phase III ZENITH CVOT is an event-driven study that will enroll approximately 11,000 patients in over 30 countries to evaluate zilebesiran 300 mg in patients with uncontrolled hypertension, despite the use of at least two standard of care antihypertensives (one being a diuretic), and with either established cardiovascular disease (CVD) or at high risk for CVD. The primary objective will be to assess the impact of zilebesiran on reducing the risk of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events (hospitalization for HF or urgent HF visit), compared to placebo.

About Zilebesiran

Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of hypertension to reduce cardiovascular risk in high unmet need populations. Zilebesiran targets angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a role in blood pressure (BP) regulation. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein, and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent biannual subcutaneous dosing and increased selectivity. Zilebesiran has demonstrated the ability to provide continuous control of blood pressure with biannual dosing in patients with mild-to-moderate hypertension as a monotherapy and in combination with standard-of-care antihypertensives, as well as in patients with high cardiovascular risk and uncontrolled hypertension despite the use of multiple background therapies. The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA or any other health authority. Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche.

Zilebesiran Phase II clinical development overview:

About Cardiovascular Disease and Hypertension

Cardiovascular disease (CVD) is a global health crisis and a leading cause of death worldwide, responsible for approximately 20 million deaths annually. Hypertension is the primary cause of and number one modifiable risk factor for CVD. An estimated one in three adults worldwide have hypertension and despite wide availability of antihypertensives, up to 80% of all patients and up to a third of treated patients do not reach and maintain blood pressure (BP) targets. Even when blood pressure appears well managed, continuous control of BP may remain suboptimal, leading to variability in BP during the 24-hour period and in the long-term, putting patients at greater risk of cardiovascular events and end organ damage. These patients require novel approaches that not only reduce BP but also lower overall cardiovascular risk.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Contacts

Media Contacts: Nicolette Baker (650) 467-6800

Advocacy Contact: Jenee Williams (650) 303-2958

Investor Contacts: Loren Kalm (650) 225-3217

Bruno Eschli +41 61 687 5284

Alnylam to Advance Zilebesiran into Global Phase 3 Cardiovascular Outcomes Trial




Alnylam to Advance Zilebesiran into Global Phase 3 Cardiovascular Outcomes Trial

– Phase 3 Trial Informed by KARDIA-3 Phase 2 Study Results Presented as a Late-Breaking Abstract at the European Society of Cardiology Congress 2025 –

– Zilebesiran Demonstrated Clinically Meaningful Reductions in Office Systolic Blood Pressure in Patients with Uncontrolled Hypertension and High Cardiovascular Risk at Month 3 Primary Endpoint, with Continuous Control Through Month 6 –

– Zilebesiran Displayed Encouraging Safety When Combined with Two or More Antihypertensives –

– Results Support Biannual Dosing Regimen and Inform Phase 3 Trial Design: Trial Expected to Initiate by Year-End 2025 –

– Alnylam to Host Webcast Investor Event on August 30, 2025, at 1:00 pm ET (7:00 pm CEST) –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced plans to initiate a Phase 3 cardiovascular outcomes trial (CVOT) to evaluate the potential of zilebesiran to reduce the risk of major adverse cardiovascular events. This decision is informed by results from the comprehensive KARDIA Phase 2 program, including KARDIA-3 results presented today as a late-breaking abstract at the European Society of Cardiology (ESC) Congress in Madrid, Spain. Zilebesiran is an investigational subcutaneously administered RNAi therapeutic which, in the KARDIA Phase 2 program, has shown reductions in blood pressure by targeting liver-expressed angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), which plays a key role in blood pressure regulation and impacts cardiovascular and renal health.

KARDIA-3, the third Phase 2 study in the KARDIA program, evaluated the efficacy and safety of zilebesiran in patients with uncontrolled hypertension and high cardiovascular (CV) risk on two or more background antihypertensives. The study met the objective of informing the design, patient population, and dose for the global Phase 3 CVOT, ZENITH (ZilebEsiraN CardIovascular OuTcome Study in Hypertension).

Results of KARDIA-3 showed a single 300 mg dose of zilebesiran resulted in clinically meaningful, placebo-adjusted reductions of office systolic blood pressure (SBP) at the Month 3 primary endpoint (-5.0 mmHg; p=0.0431) with sustained benefits out to Month 6 (-3.9 mmHg; 95% CI: -8.5, 0.7). There were no additional benefits of the 600 mg dose at Month 3 (-3.3 mmHg; p=0.1830) or Month 6 (-3.6 mmHg; 95% CI: -8.2, 1.0). The statistical testing of change in office SBP at the Month 3 primary endpoint was controlled for multiplicity, which required both doses to have a p-value of <0.05, or one dose to have a p-value of <0.025, to be considered statistically significant. As such, the study did not meet the pre-specified definition for statistical significance.

As observed in the KARDIA-2 Phase 2 study, the KARDIA-3 results support the biologically based, synergistic effects of combining zilebesiran with a diuretic-containing regimen. In patients with uncontrolled hypertension with a baseline office SBP of ≥140, despite treatment with a diuretic and at least one other antihypertensive, zilebesiran produced an enhanced effect with observed SBP reductions of at least 8 mmHg sustained out to six months.

Zilebesiran demonstrated encouraging safety in patients with comorbidities on multiple background therapies – over 90% of whom were receiving treatment with an ACE inhibitor or an Angiotensin Receptor Blocker (ARB). These findings support zilebesiran’s potential to be combined with any standard of care antihypertensive.

As a result, clinical trial applications for the ZENITH Phase 3 trial have been submitted to global regulators. Alnylam and its partner Roche expect the trial to initiate by the end of 2025. ZENITH will be a CVOT enrolling approximately 11,000 patients and evaluating zilebesiran (300 mg) every six months compared to placebo in patients with uncontrolled hypertension with either established cardiovascular disease or at high risk for cardiovascular disease on two or more antihypertensives, one being a diuretic.

“Cardiovascular disease, largely driven by uncontrolled hypertension, is a global health crisis and remains the leading addressable cause of cardiovascular morbidity and mortality,” said Pushkal Garg, M.D., Chief Research and Development Officer of Alnylam. “The KARDIA-3 results demonstrate that a single dose of zilebesiran provided continuous control of blood pressure over the 24-hour period, day and night, for up to six months, while also showing the potential to improve cardiac and renal biomarkers independent of blood pressure reduction. Taken together with the full KARDIA Phase 2 program data, these findings reinforce that targeting angiotensinogen – the most upstream precursor of the RAAS – with zilebesiran offers a differentiated approach that has the potential to improve blood pressure control and cardiovascular outcomes.”

These results add to the growing body of evidence from the KARDIA Phase 2 program, underscoring zilebesiran’s potential to address an area of significant unmet need.

“Patients with uncontrolled hypertension despite the use of multiple background therapies are at the highest risk of major adverse cardiovascular events. It is well known that reductions in systolic blood pressure of five mmHg or more can result in a reduction in cardiovascular risk,” said Neha Pagidipati, M.D., MPH, FACC, Associate Professor of Medicine, Cardiology, Duke Clinical Research Institute, and KARDIA-3 Lead Investigator. “Therefore, I’m excited by the KARDIA-3 results, which together with the additional Phase 2 data from the KARDIA program, support zilebesiran’s potential to achieve clinically meaningful, sustained blood pressure reductions in high-risk patients. This, in turn, may lead to more consistent long-term blood pressure control and improve cardiovascular outcomes. Zilebesiran’s emerging profile, now including the KARDIA-3 findings, underscores its ability to address the well-known challenges of managing patients with hypertension, and warrants further exploration in a multi-year Phase 3 cardiovascular outcomes trial.”

KARDIA-3 Cohort A Results:

The KARDIA-3 Phase 2 study included two Cohorts (A and B). Cohort A assessed zilebesiran in patients with eGFR ≥ 45 mL/min/1.73m2, while Cohort B included patients with advanced kidney dysfunction (i.e., eGFR between 30 and <45 mL/min/1.73m2). Cohort A enrolled 270 patients who were randomized to treatment with zilebesiran (300 mg or 600 mg) or placebo. Randomization was stratified by background diuretic use, baseline blood pressure, and race. The primary endpoint was change in office SBP at Month 3. Key secondary endpoints were changes in office SBP at Month 6 and change in 24-hour mean ambulatory SBP at Months 3 and 6.

At baseline, 144 (53.3%), 96 (35.6%), and 30 (11.1%) patients were on two, three, or more than three antihypertensives, respectively, with ~91% of patients taking ACE inhibitors/ARBs, ~66% of patients taking a diuretic, and ~58% of patients taking calcium channel blockers. The mean baseline office and 24-hour mean ambulatory SBP were 143.6 mmHg and 142.4 mmHg, respectively (N= 270).

• In the Cohort A overall study population, zilebesiran 300 mg achieved clinically meaningful reductions in both office and 24-hour mean ambulatory SBP at Month 3, which persisted through Month 6, compared to placebo. No incremental SBP reductions were observed with zilebesiran 600 mg at Months 3 or 6.
• Treatment with zilebesiran 300 mg produced greater SBP reductions at Month 3 and 6 in patients receiving at least two or more antihypertensives, one being a diuretic, and with office SBP ≥140 mmHg at baseline (N=110), compared to placebo.
• Reductions in blood pressure were sustained over six months and the entire 24-hour period. Incremental reductions were also observed at nighttime, a period during which blood pressure elevation is a strong predictor of cardiovascular risk.
• Zilebesiran also led to early and sustained reductions in prognostic cardiovascular and renal biomarkers (NT-proBNP and UACR) in patients with elevated biomarkers at baseline, suggesting the potential to reduce cardiovascular and renal events in high-risk patients with longer term use.
• Consistent with prior studies, zilebesiran demonstrated an encouraging safety profile. Most adverse events were mild or moderate, non-serious, and transient with few requiring intervention; rates of hyperkalemia, kidney dysfunction, and hypotension were low. Across study arms, serious adverse events were observed in 3.8% and 4.5% in zilebesiran and placebo-treated patients, respectively. No deaths were reported during the six-month double-blind period.

Results from KARDIA-3 Cohort B are expected to be presented at an upcoming medical meeting.

Alnylam and its partner Roche will now advance zilebesiran into the global Phase 3 ZENITH CVOT, which is expected to initiate by year-end 2025. ZENITH will enroll approximately 11,000 patients in over 30 countries to evaluate zilebesiran 300 mg in patients with uncontrolled hypertension, despite the use of at least two standard of care antihypertensives (one being a diuretic), and with either established cardiovascular disease (CVD) or at high risk for CVD. The primary objective will be to assess the impact of zilebesiran on reducing the risk of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events (hospitalization for HF or urgent HF visit), compared to placebo.

For additional information on Alnylam’s presentations at ESC Congress 2025, including a new exploratory analysis from the KARDIA-1 study highlighting zilebesiran’s mechanism of action in suppressing all downstream substrates of AGT, please visit Capella.

Investor Webcast Information

Alnylam management as well as Neha Pagidipati, M.D., MPH, FACC, Associate Professor of Medicine, Cardiology, Duke Clinical Research Institute, and Professor Bryan Williams, OBE, M.D., FMedSci, Chair of Medicine, University College London, will discuss the KARDIA-3 results in a live event which will be webcast on August 30, 2025, at 1:00 pm ET (7:00 pm CEST). The webcast will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Company’s website approximately two hours after the event.

About Zilebesiran

Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of hypertension to reduce cardiovascular risk in high unmet need populations. Zilebesiran targets angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), which plays a role in blood pressure (BP) regulation and impacts cardiovascular and renal health. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein, and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent biannual subcutaneous dosing and increased selectivity. Zilebesiran has demonstrated the ability to provide continuous control of BP with biannual dosing in patients with mild-to-moderate hypertension as a monotherapy and in combination with standard-of-care antihypertensives, as well as in patients with high cardiovascular risk and uncontrolled hypertension despite the use of multiple background therapies. The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA or any other health authority. Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche.

About Cardiovascular Disease and Hypertension

Cardiovascular disease (CVD) is a global health crisis and a leading cause of death worldwide, responsible for approximately 20 million deaths annually.^1,2 Hypertension is the primary cause of and number one modifiable risk factor for CVD.³ An estimated 1 in 3 adults worldwide have hypertension, and despite wide availability of antihypertensives, up to 80% of all patients, and up to a third of treated patients, do not reach and maintain blood pressure (BP) targets.⁴ Even when BP appears well managed, continuous control of BP may remain suboptimal, leading to variability in BP during the 24-hour period and in the long-term, putting patients at greater risk of cardiovascular events and end organ damage.^5-11 These patients require novel approaches that not only reduce BP, but also lower overall cardiovascular risk.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today.¹² Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine.¹³ By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made.¹² This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA.

Alnylam Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements regarding Alnylam’s plans to advance zilebesiran into a global Phase 3 cardiovascular outcomes trial (ZENITH) by year-end 2025; the number of patients who will be enrolled in the ZENITH trial, the number of countries in which those patients will be located, and the specific design of the ZENITH trial; the potential safety and efficacy of zilebesiran for the treatment of hypertension, including the potential for a single dose of zilebesiran to provide continuous control of blood pressure over a 24-hour period for up to six months while also improving cardiac and renal biomarkers independent of blood pressure reduction, that targeting angiotensinogen with zilebesiran offers a differentiated approach that has the potential to improve blood pressure control and cardiovascular outcomes, zilebesiran’s ability to be combined with any standard of care antihypertensive, zilebesiran’s potential to address an area of significant unmet need, zilebesiran’s potential to achieve clinically meaningful, sustained blood pressure reductions in high-risk patients, which may in turn lead to more consistent long-term blood pressure control and improve cardiovascular outcomes, and zilebesiran’s ability to address the well-known challenges of managing patients with hypertension; and Alnylam’s expectations regarding its aspiration to become a leading biotech company and the planned achievement of its “Alnylam P⁵ x25” strategy, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to Alnylam’s ability to successfully execute on its “Alnylam P⁵x25” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including zilebesiran; or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2024 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing Alnylam’s views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

¹ GBD 2021 Causes of Death Collaborators. Lancet. 2024;403:2100-2132.

² Lindstrom M, DeCleene N, Dorsey H, et al. J Am Coll Cardiol. 2022;80:2372-2425.

³ Yusuf S, Joseph P, Rangarajan S, et al. Lancet. 2020;395:795-808.

⁴ NCD Risk Factor Collaboration (NCD-RisC). Lancet. 2021;398:957-980.

⁵ Ebinger JE, Driver M, Ouyang D, et al. eClinicalMedicine. 2022;48:101442.

⁶ Kario K. Prog Cardiovasc Dis. 2016;59:262-281.

⁷ Doumas M, Tsioufis C, Fletcher R, et al. J Am Heart Assoc. 2017;6:e006093.

⁸ Mezue K, Goyal A, Pressman GS, et al. J Clin Hypertens. 2018;20:1247-1252.

⁹ Rothwell PM, Howard SC, Dolan E, et al. Lancet. 2010;375:895-905.

¹⁰ Tatasciore A, Renda G, Zimarino M, et al. Hypertension. 2007;50:325-332.

¹¹ Mokadem ME, Boshra H, El Hady YA, et al. J Hum Hypertens. 2019;34:641-647.

¹² Elbashir SM, Harborth J, Lendeckel W, et al. Nature. 2001;411(6836):494-498.

¹³ Zamore P. Cell. 2006;127(5):1083-1086.

Contacts

Alnylam Pharmaceuticals, Inc.


Christine Akinc

(Investors and Media)

+1-617-682-4340

Josh Brodsky

(Investors)

+1-617-551-8276

Baxdrostat demonstrated statistically significant and clinically meaningful reduction in systolic blood pressure in patients with hard-to-control hypertension in the BaxHTN Phase III ​trial




Baxdrostat demonstrated statistically significant and clinically meaningful reduction in systolic blood pressure in patients with hard-to-control hypertension in the BaxHTN Phase III ​trial

Baxdrostat 2mg lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo-adjusted) from baseline, and was generally well tolerated with no unanticipated safety findings

Full results presented at the European Society of Cardiology Congress 2025 and published in the New England Journal of Medicine

WILMINGTON, Del.–(BUSINESS WIRE)–Positive full results from the ​BaxHTN Phase III trial showed ​baxdrostat demonstrated a statistically significant and clinically meaningful reduction in mean seated systolic blood pressure (SBP) at two doses (2mg and 1mg) compared with placebo at 12 weeks. Results were seen in patients with hard-to-control (uncontrolled and resistant) hypertension who received baxdrostat or placebo on top of standard of care.

These data were presented today in a Hot Line session at the European Society of Cardiology (ESC) Congress 2025 and also simultaneously published in the New England Journal of Medicine.

Baxdrostat met the primary and all secondary endpoints in the BaxHTN Phase III trial, delivering meaningful and sustained blood pressure reductions in patients with hard-to-control hypertension. At week 12, the absolute reduction from baseline in mean seated SBP was 15.7 mmHg (95% confidence interval [CI], -17.6 to -13.7) and placebo-adjusted reduction was 9.8 mmHg (95% CI, -12.6 to -7.0; p<0.001) for the 2mg dose. For the 1mg dose, the absolute reduction from baseline was 14.5 mmHg (95% CI, -16.5 to -12.5) and placebo-adjusted reduction was 8.7 mmHg (95% CI, -11.5 to -5.8; p<0.001). The reduction in mean seated SBP with placebo was 5.8 mmHg (95% CI, -7.9 to -3.8). Results were consistent across both uncontrolled and treatment-resistant subgroups.

Baxdrostat was generally well tolerated with no unanticipated safety findings, and low rates of confirmed hyperkalemia (>6 mmol/L in both dose groups [1.1% each]) compared with placebo (0.0%). The safety profile of baxdrostat was consistent with its mechanism of action, and most adverse events were mild.

The trial also met all confirmatory secondary endpoints with baxdrostat. This included demonstration of durable long-term blood pressure reduction with baxdrostat 2mg. Both 2mg and 1mg doses also led to greater reductions in diastolic blood pressure and nearly tripled the odds of patients reaching their target SBP <130 mmHg compared with placebo.

In a prespecified exploratory analysis of a subgroup of patients, baxdrostat meaningfully reduced 24-hour and ambulatory nighttime SBP compared with placebo, key indicators of sustained blood pressure control and reduced cardiovascular risk. The 2mg dose lowered 24-hour SBP by 16.9 mmHg (95% CI, -25.6 to -8.3), and the pooled 2mg and 1mg doses lowered nighttime SBP by 11.7 mmHg (95% CI, -19.5 to -3.8). The Bax24 Phase III trial, evaluating 24-hour ambulatory effects, is expected to read out later this year.

Dr. Bryan Williams, Chair of Medicine at University College London, primary investigator, said: “Achieving a nearly 10 mmHg placebo-adjusted reduction in systolic blood pressure with baxdrostat in the BaxHTN Phase III trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease. These data show that aldosterone plays a greater role in hard-to-control hypertension than previously recognized, underscoring the importance of baxdrostat’s novel mechanism of action, and potential impact for the millions of people living with hard-to-control hypertension despite being on multiple treatments.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said: “The BaxHTN Phase III results demonstrate baxdrostat’s potential in tackling one of the toughest challenges in cardiovascular care, which is hypertension that is hard to control despite multiple therapies. We look forward to advancing our regulatory filings for baxdrostat with health authorities in the months ahead, in addition to rapidly progressing a robust clinical development program across indications where aldosterone plays a key role, including chronic kidney disease and heart failure prevention.”

There are 1.3 billion people worldwide living with hypertension.¹ In the US, approximately 50% of patients living with hypertension on multiple treatments do not have their blood pressure under control.² Aldosterone dysregulation is increasingly recognized as one of the key biological drivers of the disease, contributing to elevated cardiovascular and renal risk.^3,4 A large meta-analysis found that lowering systolic blood pressure by 10 mmHg can reduce the risk of major adverse cardiovascular events by around 20%,⁵ underscoring the urgent need for new treatments that target hypertension at its source.

Baxdrostat is a potential first-in-class, highly selective aldosterone synthase inhibitor (ASI) that targets one of the hormones driving elevated blood pressure and increased cardiovascular and renal risk. It is currently being investigated in clinical trials enrolling more than 20,000 patients globally, as a monotherapy for hypertension and primary aldosteronism, and in combination with dapagliflozin for chronic kidney disease and hypertension, and the prevention of heart failure in patients with hypertension.

Notes

Hard-to-control hypertension

Hypertension is a medical condition characterized by consistently high blood pressure levels, affecting an estimated 1.3 billion people worldwide.^1,6,7 Over time, this can damage blood vessels and vital organs, increasing the risk of serious health problems such as heart attack, stroke, heart failure and kidney disease.^6,7

Hard-to-control (uncontrolled and resistant) hypertension remains a major public health challenge.¹ Despite lifestyle changes and the use of multiple medications, approximately 50% of patients in the US who are being treated for hypertension still do not have their blood pressure under control.^1,2 Uncontrolled hypertension refers to persistently elevated blood pressure despite the use of two or more medications, while resistant hypertension, a more severe form, remains elevated despite treatment with three or more medications.^2,6

A key contributor to hard-to-control hypertension is aldosterone, a hormone that raises blood pressure by promoting sodium and water retention.^3,4 Elevated aldosterone levels, along with factors such as obesity, high salt intake, and various genetic or secondary conditions,⁸ are strongly associated with poor blood pressure control. When left untreated, hypertension significantly increases the risk of cardiovascular and kidney-related complications.^6,7

BaxHTN trial

The BaxHTN Phase III trial⁹ had three components to it that support the following endpoints: The primary endpoint was assessed during a 12-week double-blind, placebo-controlled period. A total of 796 patients were characterized in a 1:1:1 ratio to receive baxdrostat 2mg, 1mg or placebo once daily. The primary efficacy endpoint was the difference in mean change from baseline in seated SBP at week 12 between participants treated with baxdrostat (2mg or 1mg separately) and participants treated with placebo. Persistence of efficacy was assessed during a randomized withdrawal period from week 24 to week 32. Approximately 300 patients treated with baxdrostat 2mg were re-randomized in a 2:1 ratio to either continue receiving baxdrostat 2mg or placebo for the 8 weeks. SBP at the end of the 8 weeks was compared with placebo and the baxdrostat 2mg dose. Long-term safety is assessed at the end of the 52 weeks compared to a standard of care arm.

Additional confirmatory secondary endpoints include the effect of baxdrostat versus placebo on seated SBP at week 12 in the resistant hypertension subpopulation, the effect of baxdrostat versus placebo on seated diastolic blood pressure at week 12, and proportion of participants achieving seated SBP less than 130 mmHg at week 12. Occurrence of adverse events was also evaluated.

Baxdrostat

Baxdrostat is a potential first-in-class, highly selective and potent, oral, small molecule that inhibits aldosterone synthase,¹⁰ an enzyme encoded by the CYP11B2 gene, which is responsible for the synthesis of aldosterone in the adrenal gland.³ In clinical trials, baxdrostat was observed to significantly lower aldosterone levels without affecting cortisol levels across a wide range of doses.^11,12 Baxdrostat is currently being investigated in clinical trials as a monotherapy for hypertension^9,13,14 and primary aldosteronism,¹⁵ and in combination with dapagliflozin for chronic kidney disease^16,17 and hypertension, and the prevention of heart failure in patients with hypertension.¹⁸

AstraZeneca acquired baxdrostat through its purchase of CinCor Pharma, Inc. in February 2023.¹⁹ A contingent value right of $10 per share in cash ($0.5 billion) is payable to former CinCor shareholders upon the submission of a new drug application either in the US or Europe.¹⁹

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.

References

1. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957-980.
2. Carey RM, et al. Prevalence of apparent treatment-resistant hypertension in the United States: comparison of the 2008 and 2018 American Heart Association scientific statements on resistant hypertension [including online supplement]. Hypertension. 2019;73(2):424-431.
3. Cannavo A, et al. Aldosterone and mineralocorticoid receptor system in cardiovascular physiology and pathophysiology. Oxid Med Cell Longev. 2018;2018:1204598.
4. Inoue K, et al. Serum aldosterone concentration, blood pressure, and coronary artery calcium: the Multi-Ethnic Study of Atherosclerosis [including online supplement]. Hypertension. 2020;76(1):113-120.
5. Ettehad, D. et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis; Lancet 2016;387:957–67.
6. McEvoy JW, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. EurHeart J. 2024;45(38):3912-4018.
7. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-1324.
8. van Oort S, et al. Association of cardiovascular risk factors and lifestyle behaviors with hypertension: a mendelian randomization study. Hypertension. 2020;76(6):1971-1979.
9. ClinicalTrials.gov. A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (BaxHTN). Available at: https://clinicaltrials.gov/study/NCT06034743. Accessed August 2025.
10. Bogman K, et al. Preclinical and early clinical profile of a highly selective and potent oral inhibitor of aldosterone synthase (CYP11B2). Hypertension. 2017;69:189-96.
11. Freeman, MW et al. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023;(46)108–118.
12. Freeman MW, et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. NEJM. 2023;388:395-405.
13. ClinicalTrials.gov. A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension (Bax24). Available at: https://clinicaltrials.gov/study/NCT06168409. Accessed August 2025.
14. ClinicalTrials.gov. A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (BaxAsia). Available at: https://clinicaltrials.gov/study/NCT06344104. Accessed August 2025.
15. ClinicalTrials.gov. A Study to Assess Efficacy and Safety of Baxdrostat in Participants With Primary Aldosteronism (BaxPA). Available at: https://clinicaltrials.gov/study/NCT07007793. Accessed August 2025.
16. ClinicalTrials.gov. A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure (BaxDuo-Pacific). Available at: https://clinicaltrials.gov/study/NCT06742723. Accessed August 2025.
17. ClinicalTrials.gov. A Phase III Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin on CKD Progression in Participants With CKD and High Blood Pressure. Available at: https://clinicaltrials.gov/study/NCT06268873. Accessed August 2025.
18. ClinicalTrials.gov. A Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin (Prevent-HF). ClinicalTrials.gov identifier: NCT06677060. Available at: https://clinicaltrials.gov/study/NCT06677060. Accessed August 2025.
19. AstraZeneca 2023. Acquisition of CinCor Pharma complete. Available at: https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html. Accessed August 2025.

Contacts

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Merck Provides New Results for VERQUVO® (vericiguat) in Patients with Chronic Heart Failure and Reduced Ejection Fraction




Merck Provides New Results for VERQUVO® (vericiguat) in Patients with Chronic Heart Failure and Reduced Ejection Fraction

Results from the Phase 3 VICTOR trial and a pooled analysis of the VICTOR and VICTORIA trials were presented today at the ESC Congress 2025 and simultaneously published in The Lancet

RAHWAY, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results evaluating VERQUVO^® (vericiguat) in adult patients with stable chronic heart failure and reduced ejection fraction (HFrEF). The Phase 3 VICTOR trial comparing the efficacy of VERQUVO to placebo in patients with HFrEF without a recent worsening heart failure event treated with guideline-directed medical therapy (GDMT) did not reach statistical significance for its primary endpoint of combined time to first event of cardiovascular death or hospitalization for heart failure. In a separate pre-specified pooled analysis of patient-level data from the complementary Phase 3 VICTOR and VICTORIA trials, VERQUVO reduced the risk of the composite primary endpoint of cardiovascular death or heart failure hospitalization across these patients with a broad range of disease severity. Results from both analyses were presented today at the European Society of Cardiology (ESC) Congress 2025 in a Hot Line session and simultaneously published in The Lancet.

VERQUVO was initially studied and approved in patients with worsening chronic heart failure and ejection fraction less than 45% following a worsening heart failure event based on the pivotal Phase 3 VICTORIA trial. Participants in the VICTOR trial represented a well-treated group of ambulatory HFrEF patients on GDMT and 47.5% of participants had no history of hospitalization for heart failure. Results showed that VERQUVO did not significantly reduce the risk of the primary composite outcome of time to cardiovascular death or hospitalization for heart failure, which occurred in 18% (n=549/3,053) of patients treated with VERQUVO compared to 19.1% (n=584/3,052) in the placebo group (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.83-1.04; p=0.22). For the key secondary endpoints, cardiovascular death was numerically lower with VERQUVO (9.6%) compared to placebo (11.3%) (HR 0.83; 95% CI 0.71-0.97) and heart failure hospitalization occurred in 11.4% of patients receiving VERQUVO and 11.9% of patients receiving placebo (HR 0.95; 95% CI 0.82–1.10). The overall safety profile of VERQUVO in the VICTOR trial was consistent with previous clinical trials.

“By studying patients without recent heart failure hospitalizations, the Phase 3 VICTOR trial expands our understanding of VERQUVO across the full spectrum of chronic heart failure patients with reduced ejection fraction,” said Dr. Joerg Koglin, senior vice president and head of general medicine, global clinical development, Merck Research Laboratories. “Together with the previously communicated results in VICTORIA in patients with worsening chronic heart failure and ejection fraction less than 45% following a worsening heart failure event, the results today provide valuable information and add to our understanding of heart failure and VERQUVO. We are grateful to the patients and investigators for their participation in these studies and remain confident in the role of VERQUVO for its approved indication for patients with HFrEF following a recent heart failure event and with ejection fraction less than 45% based on the pivotal Phase 3 VICTORIA trial.”

The Phase 3 VICTORIA trial focused exclusively on a population with worsening chronic HFrEF at high risk for cardiovascular mortality and repeated heart failure hospitalizations. In a separate pre-specified pooled analysis across VICTOR and VICTORIA, VERQUVO’s benefit was examined in a large and broad cohort. In this pooled analysis of 11,155 HFrEF patients, VERQUVO showed a statistically significant risk reduction across the primary composite endpoint of cardiovascular death or heart failure hospitalization and its components as secondary endpoints, in a broad spectrum of patients with HFrEF. No new safety signals, beyond those reported in the individual trials, emerged in the pooled analysis.

“While the VICTOR trial did not meet its primary endpoint, the separate pooled analysis across both VICTOR and VICTORIA did demonstrate a statistically significant reduction in the primary composite endpoint of heart failure hospitalization and cardiovascular deaths in patients with heart failure and reduced ejection fraction across the disease severity,” said Javed Butler, MD, MPH, MBA, President of the Baylor Scott and White Research Institute and Professor of Medicine at University of Mississippi in Jackson, Mississippi.

The positive benefit-risk profile of VERQUVO in its approved indication in patients with HFrEF following a recent heart failure event based on the pivotal Phase 3 VICTORIA trial remains unchanged. In the U.S., VERQUVO is approved for the reduction of risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics in adults with symptomatic chronic heart failure and ejection fraction less than 45%.

About VICTOR

VICTOR (VerICiguaT in adults with ChrOnic heart failure and Reduced ejection fraction) (NCT05093933) was a randomized, double-blind, placebo-controlled, multicenter, event-driven Phase 3 study investigating the efficacy and safety of VERQUVO in adult patients with symptomatic chronic heart failure (New York Heart Association [NYHA] class II-IV) and a left ventricular ejection fraction (LVEF) of 40% or less. It enrolled 6,105 patients with chronic heart failure with reduced ejection fraction (HFrEF), who had not had a recent hospitalization for heart failure within 6 months or the need for outpatient intravenous diuretics within 3 months before randomization. Patients receiving contemporary guideline-directed medical therapy (GDMT), including SGLT2-inhibitors and angiotensin receptor-neprilysin inhibitor (ARNI), were randomized to receive either VERQUVO or placebo. VICTOR was the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational GDMT, in a compensated ambulatory heart failure population. Merck and Bayer AG are co-developers of the VICTOR trial. The study was executed by Merck.

About VICTORIA

VICTORIA (NCT02861534) was a randomized, placebo-controlled, parallel-group, multi-center, double-blind, Phase 3 study of VERQUVO versus placebo when given in combination with available heart failure therapies in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) following a decompensation event, defined as heart failure hospitalization or receiving an intravenous diuretic for heart failure without hospitalization. The primary endpoint of the study was the composite of time to first occurrence of cardiovascular death or heart failure hospitalization. Secondary endpoints included time to occurrence of cardiovascular death, time to first occurrence of heart failure hospitalization, time to total heart failure hospitalizations (including first and recurrent events), time to the composite of all-cause mortality or heart failure hospitalization, and time to all-cause mortality. The study enrolled 5,050 patients who were randomized to receive either VERQUVO once daily (titrated up to 10 mg) or placebo when given in combination with available heart failure therapies. The study, which was co-sponsored by Merck and Bayer, was conducted in collaboration with the Canadian VIGOUR Centre and the Duke Clinical Research Institute in more than 600 centers in 42 countries.

About VERQUVO (vericiguat)

VERQUVO is an oral once daily stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, VERQUVO augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.

VERQUVO is FDA-approved to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for HF or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.

Selected Safety Information for VERQUVO (vericiguat) tablets (2.5 mg, 5 mg, and 10 mg)

WARNING: EMBRYO-FETAL TOXICITY

Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment. Do not administer VERQUVO to a pregnant female because it may cause fetal harm.

VERQUVO is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators. VERQUVO is contraindicated in pregnancy. Based on data from animal reproduction studies, VERQUVO may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment. Advise females of reproductive potential to use effective contraception during treatment with VERQUVO and for at least one month after the final dose.

In a clinical trial, the most commonly observed adverse events with VERQUVO vs placebo, occurring at a frequency greater than or equal to 5%, were hypotension (16% vs 15%) and anemia (10% vs 7%).

Concomitant use of VERQUVO with PDE-5 inhibitors is not recommended because of the potential for hypotension.

There are no data on the presence of VERQUVO in human milk, the effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from VERQUVO, advise women not to breastfeed during treatment with VERQUVO.

About Heart Failure with Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF), formerly known as systolic heart failure, is characterized by the compromised ability of the heart to pump blood sufficiently during its contraction phase. In the U.S., approximately 6.2 million adults (20 years of age and older) have heart failure, and approximately 50% of heart failure patients have HFrEF. An observational, cohort analysis of PINNACLE registry data showed that approximately half of patients with worsening chronic HFrEF are rehospitalized within 30 days of a worsening event, and an estimated one in five patients with worsening chronic HFrEF will die within two years.

About the Worldwide Collaboration between Merck and Bayer

Since October 2014, Bayer and Merck (known as MSD outside the U.S. and Canada) have pursued a worldwide collaboration in the field of sGC modulators. The collaboration brings together two leading companies that have stated their intent to fully evaluate this therapeutic class in areas of unmet medical need. The vericiguat program is being co-developed by Bayer and MSD. MSD has the commercial rights to vericiguat in the U.S. and Bayer has the exclusive commercial rights in the rest of world. The companies share equally the costs of the development of vericiguat.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), LinkedIn and YouTube.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information, including Boxed Warning, for VERQUVO (vericiguat) at https://www.merck.com/product/usa/pi_circulars/v/verquvo/verquvo_pi.pdf and Medication Guide at https://www.merck.com/product/usa/pi_circulars/v/verquvo/verquvo_mg.pdf.

Contacts

Media Contacts:

Julie Cunningham, (617) 519-6264

Elizabeth Sell, (484) 689-9978

Investor Contacts:

Peter Dannenbaum, (732) 594-1579

Ayn Wisler, (917) 691-6218

Exelixis Announces Appointment of Dana T. Aftab, Ph.D. as Executive Vice President, Research and Development




Exelixis Announces Appointment of Dana T. Aftab, Ph.D. as Executive Vice President, Research and Development

– Dr. Aftab has served for over 25 years at Exelixis and has been instrumental in driving the company’s scientific innovation and development activities –

ALAMEDA, Calif.–(BUSINESS WIRE)–Exelixis, Inc. (Nasdaq: EXEL) today announced it has appointed Dana T. Aftab, Ph.D., as its Executive Vice President, Research and Development. In this new role, Dr. Aftab will oversee all aspects of the company’s drug discovery, translational research, product development and medical affairs activities.

“Dana has been an integral part of the Exelixis team for more than 25 years, with deep expertise that spans the drug discovery and development continuum. He’s been a key contributor to many of Exelixis’ most important milestones, including the discovery, development and introduction of cabozantinib, which he and the broader Exelixis team grew from an initial orphan drug indication into a global oncology franchise,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. “Dana is an excellent choice to lead Exelixis’ wide-ranging product development organization as the team maximizes the opportunities for our portfolio, which in addition to cabozantinib includes zanzalintinib, our third-generation oral tyrosine kinase inhibitor that is the subject of multiple pivotal trials, as well as our earlier stage pipeline of promising small molecules and biotherapeutics.”

Dr. Aftab joined Exelixis in 1998, and since then has played a key role in the discovery and development of the company’s flagship medicine, CABOMETYX® (cabozantinib), which is currently the leading tyrosine kinase inhibitor in the U.S. for both the treatment of advanced renal cell carcinoma and advanced neuroendocrine tumors. During his tenure at Exelixis, Dr. Aftab held diverse roles across the company’s research and development organizations, and most recently served as Executive Vice President, Discovery and Translational Research and Chief Scientific Officer since December 2022. In that role he has overseen the development of the company’s early pipeline, as well as of the translational medicine and clinical pharmacology teams supporting work streams across the spectrum of discovery research and product development. Dr. Aftab holds a Ph.D. degree in pharmacology from Yale University and conducted postdoctoral work at the University of California, Berkeley in the field of oncogene signaling.

Amy Peterson, M.D., who served as Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer since August 2023 has departed Exelixis.

About Exelixis

Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules and biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX^® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements, including, without limitation, statements related to Exelixis’ senior officer transitions. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation, factors affecting Exelixis discussed under the caption “Risk Factors” in Exelixis’ Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 11, 2025, and in Exelixis’ subsequent filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks.

Contacts

Investors Contact:
Susan Hubbard
EVP, Public Affairs and
Investor Relations
Exelixis, Inc.
(650) 837-8194
shubbard@exelixis.com

Media Contact:
Hal Mackins
For Exelixis, Inc.
(415) 994-0040
hal@torchcommunications.com

GenSight Biologics Postpones Release of 2025 Half-Year Financial Results




GenSight Biologics Postpones Release of 2025 Half-Year Financial Results

PARIS–(BUSINESS WIRE)–Regulatory News:

GenSight Biologics (“GenSight Biologics” or the “Company“) (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the release of its half-year financial results, originally scheduled for September 19, 2025, has been postponed to September 29, 2025, after the market closes.

The postponement allows the Company’s external auditors to complete all necessary audit procedures to the highest professional standards. The Company confirms that the postponement relates only to the time required for the audit rather than to any material issues with the financial statements. The extension permits full compliance with regulatory requirements and maintains the Company’s commitment to accurate and transparent financial reporting.

The Company’s Audit Committee and Board of Directors meetings have been rescheduled accordingly:

• Audit Committee: postponed to September 24, 2025
• Board Meeting: postponed to September 26, 2025

The half-year results will be made available in the investor relations section of the Company’s website immediately following the September 29 announcement.

About GenSight Biologics S.A.

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, GS010 (lenadogene nolparvovec)/GS010 is in Phase III in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. The product candidate GS010 is currently in clinical development, has not to date been granted marketing authorization in France or any other jurisdiction, and is therefore not available commercially.

Contacts

GenSight Biologics
Chief Financial Officer

Jan Eryk Umiastowski

jeumiastowski@gensight-biologics.com

Binge Eating Disorders Global Market Research Report 2025-2035 | Growth Influenced by Rising Prevalence, Improved Diagnosis, Mental Health Awareness, and Advances in Patient-Centric Treatments – ResearchAndMarkets.com




Binge Eating Disorders Global Market Research Report 2025-2035 | Growth Influenced by Rising Prevalence, Improved Diagnosis, Mental Health Awareness, and Advances in Patient-Centric Treatments – ResearchAndMarkets.com

DUBLIN–(BUSINESS WIRE)–The “Binge Eating Disorders Market – A Global and Regional Analysis: Focus on Drug Class and Region – Analysis and Forecast, 2025-2035” report has been added to ResearchAndMarkets.com’s offering.

BED is characterized by recurrent episodes of excessive food consumption accompanied by feelings of loss of control and distress, impacting both psychological and physical health. Notably, advances in screening tools, behavioural therapies, and pharmacological treatments are enabling earlier and more accurate diagnosis, boosting demand for personalized intervention strategies.

However, challenges such as social stigma, limited access to specialized care in low-resource settings, and reimbursement barriers continue to restrict market penetration. Additionally, the heterogeneous nature of BED symptoms and the requirement for integrated, long-term care complicate treatment standardization and scalability. Nevertheless, increasing government initiatives, growing investment in mental health research, and expanded patient support programs are fostering new growth opportunities. Collaborative efforts among healthcare providers, researchers, and advocacy organizations are advancing clinical outcomes and improving quality of life for individuals affected by BED.

Impact

Technological advancements in digital health, teletherapy, and data analytics are significantly improving the diagnosis and management of binge eating disorders (BED). Innovations such as AI-powered screening tools and mobile health applications enable more accurate identification of symptoms and personalized treatment plans. The rise of digital therapeutics and remote counselling platforms is expanding access to behavioural interventions, especially in underserved or remote regions.

Anticonvulsant medications hold the largest market share. This dominance is attributed to robust clinical evidence supporting their efficacy in reducing binge episode frequency and severity. Topiramate has demonstrated significant effectiveness in clinical trials, leading to its widespread adoption in treating moderate to severe BED.

North America holds the highest market share in the binge eating disorders (BED) market, primarily driven by increased awareness, better diagnostic facilities, and higher healthcare expenditure in the region. The U.S. has a well-established healthcare infrastructure and strong government initiatives focused on mental health, facilitating early diagnosis and treatment of BED. Additionally, the presence of major pharmaceutical companies actively investing in research and development for novel BED therapies further consolidates North America’s leading position.

How can this report add value to an organization?

Product/Innovation: This report provides comprehensive insights into the current trends in binge eating disorders, helping companies identify opportunities for drug and technology development. Organizations can leverage these insights to design therapies, medications, and platforms tailored to the needs of patients suffering from binge eating disorders, improving outcomes and enhancing market penetration.

Competitive: A detailed competitive landscape analysis helps organizations benchmark their market standing against key players. By understanding the strengths and weaknesses of competitors, companies can position themselves more effectively in the global binge eating disorders market.

Demand Drivers and Limitations

Demand Drivers for the Global Binge Eating Disorders Market:

• The growing prevalence and diagnosis of binge eating disorder globally and expanding the patient pool. This increased detection fuels demand for effective treatments.
• Enhanced mental health awareness and reduced stigma encourage more individuals to seek professional help. Greater acceptance supports higher treatment adoption rates.
• Advancements in treatment options and patient centric care models improve outcomes. Personalized approaches are attracting more patients to engage in care.

Limitations for the Global Binge Eating Disorders Market:

• Underdiagnosis remains a significant issue due to social stigma and limited public awareness. This results in many patients not receiving timely or appropriate treatment.
• The high cost of innovative therapies restricts access for a large portion of the patient population. Affordability remains a barrier, especially in lower-income regions.
• Regulatory hurdles contribute to prolonged approval timelines for new drugs. These delays slow down the availability of advanced treatment options in the market.

Key Market Players and Competition Synopsis

The companies profiled in this report have been selected based on their market presence, product portfolio, and competitive positioning in the global binge eating disorders market

• Eli Lilly and Company
• Amneal Pharmaceuticals, Inc.
• Takeda Pharmaceutical, Ltd.
• Tryp Therapeutics Inc.
• Tonix Pharmaceuticals Corp.
• Sumitomo Pharma Ltd.
• VIVUS Inc
• Novartis AG
• Pfizer Inc.

Key Topics Covered:

1. Global Binge Eating Disorders Market: Industry Analysis

1.1 Market Overview and Ecosystem

1.2 Epidemiological Analysis

1.3 Key Market Trends

1.3.1 Impact Analysis

1.4 Regulatory Landscape

1.5 Pipeline Analysis

1.6 Market Dynamics

1.6.1 Overview

1.6.2 Market Drivers

1.6.3 Market Restraints

1.6.4 Market Opportunities

2. Global Binge Eating Disorders Market (by Drug Class), Value ($million), 2023-2035

2.1 Antidepressant

2.2 Anticonvulsant

2.3 Anti-obesity

2.4 Others

3. Global Binge Eating Disorders Market (by Region), Value ($Million), 2023-2035

3.1 North America

3.1.1 Market Dynamics

3.1.2 Market Sizing and Forecast

3.1.3 North America Binge Eating Disorders Market, by Country ($Million), 2023-2035

3.1.3.1 U.S.

3.1.3.2 Canada

3.2 Europe

3.2.1 Market Dynamics

3.2.2 Market Sizing and Forecast

3.2.3 Europe Binge Eating Disorders Market, by Country ($Million), 2023-2035

3.2.3.1 U.K.

3.2.3.2 France

3.2.3.3 Germany

3.2.3.4 Italy

3.2.3.5 Spain

3.2.3.6 Rest-of-Europe

3.3 Asia-Pacific

3.3.1 Market Dynamics

3.3.2 Market Sizing and Forecast

3.3.3 Asia-Pacific Binge Eating Disorders Market, by Country ($Million), 2023-2035

3.3.3.1 Japan

3.3.3.2 China

3.3.3.3 India

3.3.3.4 Australia

3.3.3.5 South Korea

3.3.3.6 Rest-of-Asia-Pacific

3.4 Rest-of-the-World

3.4.1 Market Dynamics

3.4.2 Market Sizing and Forecast Rest-of-the-World Binge Eating Disorders Market, by Type ($Million), 2023-2035

3.4.3 Rest-of-the-World Binge Eating Disorders Market, by Country ($Million), 2023-2035

3.4.3.1 Latin America

3.4.3.2 Middle East and Africa

4. Competitive Landscape and Company Profiles

4.1 Competitive Landscape

4.1.1 Mergers and Acquisitions

4.1.2 Partnership, Alliances and Business Expansion

4.1.3 New Offerings

4.1.4 Regulatory Activities

4.1.5 Funding Activities

4.2 Company Profiles

4.2.1 Eli Lilly and Company

4.2.1.1 Overview

4.2.1.2 Top Products / Product Portfolio

4.2.1.3 Top Competitors

4.2.1.4 Target Customers/End-Users

4.2.1.5 Key Personnel

4.2.1.6 Analyst View

4.2.2 Amneal Pharmaceuticals, Inc.

4.2.3 Takeda Pharmaceutical, Ltd.

4.2.4 Tryp Therapeutics Inc

4.2.5 Tonix Pharmaceuticals Corp.

4.2.6 Sumitomo Pharma Ltd.

4.2.7 VIVUS Inc

4.2.8 Novartis AG

4.2.9 Pfizer Inc.

5. Research Methodology

For more information about this report visit https://www.researchandmarkets.com/r/rrk8fm

About ResearchAndMarkets.com

ResearchAndMarkets.com is the world’s leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Contacts

ResearchAndMarkets.com

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press@researchandmarkets.com

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Alpha Cognition Inc. (Nasdaq: ACOG) Announces Participation in Key September Investor Conferences




Alpha Cognition Inc. (Nasdaq: ACOG) Announces Participation in Key September Investor Conferences

VANCOUVER, British Columbia & DALLAS–(BUSINESS WIRE)–Alpha Cognition Inc. (Nasdaq: ACOG), a commercial-stage biopharmaceutical company dedicated to developing innovative treatments for neurodegenerative diseases, today announced that Chief Executive Officer Michael McFadden will present at two prominent healthcare investor conferences this September.

• Cantor Global Healthcare Conference 2025
  Date/Time: Friday, September 5, 7:00 a.m. ET
• H.C. Wainwright & Co. Healthcare Conference 2025
  Date/Time: Tuesday, September 9, 2:00 p.m. ET

Presentation transcripts will be made available on Alpha Cognition’s website following the events and will remain accessible for 30 days.

About Alpha Cognition Inc.

Alpha Cognition Inc. is a commercial stage, biopharmaceutical company dedicated to developing treatments for patients suffering from neurodegenerative diseases, such as Alzheimer’s disease and Cognitive Impairment with mild Traumatic Brain Injury (“mTBI”), for which there are currently no approved treatment options.

ZUNVEYL is a patented drug approved as a new generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ZUNVEYL’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is also being developed in combination with memantine to treat moderate to severe Alzheimer’s dementia, and as an intranasal formulation for Cognitive Impairment with mTBI.

Forward-looking Statements

This news release includes forward-looking statements within the meaning of applicable securities laws. Except for statements of historical fact, any information contained in this news release may be a forward-looking statement that reflects the Company’s current views about future events and are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. In some cases, you can identify forward‐looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “target,” “seek,” “contemplate,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Although the Company believes to have a reasonable basis for each forward-looking statement, we caution you that these statements are based on a combination of facts and factors currently known by us and our expectations of the future, about which we cannot be certain. The Company cannot assure that the actual results will be consistent with these forward-looking statements. These forward-looking statements are subject to certain risks, including risks regarding our ability to raise sufficient capital to implement our plans to commercialize ZUNVEYL, risks regarding the efficacy and tolerability of ZUNVEYL, risks related to ongoing regulatory oversight on the safety of ZUNVEYL, risk related to market adoption of ZUNVEYL, risks related to the Company’s intellectual property in relation to ZUNVEYL, risks related to the commercial manufacturing, distribution, marketing and sale of ZUNVEYL, risks related to product liability and other risks as described in the Company’s filings with Canadian securities regulatory authorities and available at www.sedar.com and the Company’s filings with the United States Securities and Exchange Commission (the “SEC”), including those risk factors under the heading “Risk Factors” in the Company’s [Form S-1/A registration statement as filed with the SEC on November 6, 2024 and available at www.sec.gov.] These forward‐looking statements speak only as of the date of this news release and the Company undertakes no obligation to revise or update any forward‐looking statements for any reason, even if new information becomes available in the future, except as required by law.

Contacts

Investor Relations

IR@alphacognition.com
https://www.alphacognition.com/