June 2025 cardiology roundup: key approvals, significant clinical trials & research trends

June was a dynamic month in cardiovascular medicine, marked by notable regulatory approvals and clinical trial progress across several therapeutic areas. Advances in hypertension management, lipid lowering and cardiometabolic care continue to shape the treatment landscape, while evolving data in pulmonary arterial hypertension underscore the importance of ongoing innovation. This month’s roundup highlights the developments poised to impact clinical practice and patient outcomes.

Approvals

FDA Approves First Triple Combination Pill for Initial Hypertension Therapy

The FDA has approved telmisartan/amlodipine/indapamide for the treatment of hypertension in adults, including as initial therapy.¹ This fixed-dose combination is the first FDA-approved triple therapy available in a single pill for patients beginning hypertension treatment who are likely to require multiple agents to achieve blood pressure targets. Available in three dose strengths, including two low-dose options, the therapy combines an angiotensin receptor blocker, a calcium channel blocker, and a non-thiazide sulfonamide with an indole ring.

Approval was based on the results from two phase III trials, GMRx2_ACT (ClinicalTrials.gov identifier: NCT04518293) and GMRx2_PCT (ClinicalTrials.gov identifier: NCT04518306), which demonstrated statistically significant blood pressure reductions compared to placebo and dual-component comparators.^2,3 Current hypertension guidelines increasingly support early use of combination therapy, particularly in single-pill formulations, to improve control rates. Nearly half of American adults have hypertension, yet only about 25% have adequately controlled blood pressure, underscoring the potential clinical utility of this new treatment option.⁴

Clinical Trial Data

HYPERION Phase III Trial Demonstrates Reduced Risk of Clinical Worsening with Sotatercept-csrk in Recently Diagnosed Pulmonary Arterial Hypertension

The phase III HYPERION (ClinicalTrials.gov identifier: NCT04811092) trial met its primary endpoint, demonstrating that sotatercept-csrk, when added to background therapy, significantly reduced the risk of time to clinical worsening (TTCW) events in adults with recently diagnosed pulmonary arterial hypertension (PAH, WHO Group 1).^5,6 Sotatercept is a fusion protein that inhibits activin signalling within the TGF-β superfamily, modulating vascular proliferation.

The randomized, double-blind, placebo-controlled study enrolled 320 participants with functional class II or III symptoms and an intermediate or high risk of disease progression, diagnosed within 12 months of study screening. Clinical worsening was defined as a composite of all-cause death, non-planned PAH-related hospitalization ≥24 hours, atrial septostomy, lung transplantation or PAH deterioration. At baseline, 72.2% (231/320) of participants were receiving dual and 27.8% (89/320) were receiving triple background therapy for a minimum of 90 days before screening. A total of 83.4% (267/320) of participants were not on prostacyclin infusion.

The trial was stopped early following an interim analysis and data review from across the clinical program. The safety profile of sotatercept-csrk in HYPERION was generally consistent with previous studies. Results will be presented at a future scientific meeting.

Phase III CORALreef Trials Confirm LDL-C Reductions with Enlicitide Decanoate in Statin-Treated Hyperlipidaemia

The phase III CORALreef trials evaluated enlicitide decanoate, an investigational oral PCSK9 inhibitor, in adults with hyperlipidemia already receiving statin therapy.⁷ Topline data from the studies demonstrated statistically significant and clinically meaningful reductions in low-density lipoprotein cholesterol (LDL‑C) compared to placebo (CORALreef HeFH; ClinicalTrials.gov identifier: NCT05952869) and compared to ezetimibe, bempedoic acid and their combination (CORALreef AddOn; ClinicalTrials.gov identifier: NCT06450366).^8,9

Both trials met all primary and key secondary endpoints at Week 24 (CORALreef HeFH) and Week 8 (CORALreef AddOn), with no clinically meaningful difference in adverse events or serious adverse events between treatment arms. CORALreef HeFH enrolled adults with heterozygous familial hypercholesterolaemia (HeFH) at risk of atherosclerotic cardiovascular disease (ASCVD), who were treated with statins, while CORALreef AddOn assessed adults with hyperlipidaemia at risk of ASCVD, who were treated with statins. Enlicitide is a novel, oral PCSK9 inhibitor, designed to prevent the interaction of PCSK9 with LDL receptors and, therefore, lower LDL-C. These findings support its potential as the first oral PCSK9-targeted therapy pending results from the full CORALreef program, with presentation planned at an upcoming scientific congress.

STRIDE Data Highlights Vascular Benefits of Semaglutide in Type 2 Diabetes

A new subanalysis of the STRIDE trial (ClinicalTrials.gov identifier: NCT04560998), presented at ADA 2025, suggests semaglutide 1.0 mg improves walking ability and quality of life in people with type 2 diabetes and peripheral artery disease (PAD), regardless of baseline HbA1c, duration of diabetes, or use of SGLT2 inhibitors.^10-2 The analysis showed that semaglutide reduced the risk of PAD progression by 54% and was well tolerated, reinforcing its potential vascular benefits beyond glycaemic control. STRIDE was a 52-week, double-blind, placebo-controlled trial that randomized 792 participants to semaglutide or placebo; the primary analysis showed semaglutide significantly improved maximum and pain-free walking distances, as well as quality-of-life scores, when compared to placebo.

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Phase II TROPOS Trial Terminated Early

The phase II TROPOS trial (ClinicalTrials.gov identifier: NCT05975905) evaluating cibotercept in combination with background therapy for pulmonary arterial hypertension (PAH) was terminated early due to safety concerns, including pericardial effusions observed across multiple dose arms.^13,14 Based on the totality of safety and efficacy data, further development of cibotercept for PAH has been discontinued.

References

1. Pharmacy Times. FDA Approves First, Only Single-Pill Triple Combination for Treatment of Hypertension. 2025. [Press release] Available at: www.pharmacytimes.com/view/fda-approves-first-only-triple-combination-agent-for-treatment-of-hypertension (accessed 8 July 2025).
2. ClinicalTrials.gov. Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension (GMRx2_ACT). ClinicalTrials.gov identifier: NCT04518293. Available at: https://clinicaltrials.gov/study/NCT04518293 (accessed 8 July 2025).
3. ClinicalTrials.gov. Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (GMRx2_PCT). ClinicalTrials.gov identifier: NCT04518306. Available at: https://clinicaltrials.gov/study/NCT04518306 (accessed 8 July 2025).
4. CDC. High Blood Pressure Facts. 2025. Available at: www.cdc.gov/high-blood-pressure/data-research/facts-stats/index.html (accessed 8 July 2025).
5. Businesswire. Merck Announces Phase 3 HYPERION Study of WINREVAIR™ (sotatercept-csrk) Met Primary Endpoint in Recently Diagnosed Adults with Pulmonary Arterial Hypertension (PAH). 2025. [Press release]. Available at: www.businesswire.com/news/home/20250623646523/en/ (accessed 8 July 2025).
6. ClinicalTrials.gov. Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/​A011-13) (HYPERION). ClinicalTrials.gov identifier: NCT04811092. Available at: https://clinicaltrials.gov/study/NCT04811092 (accessed 8 July 2025).
7. Businesswire. Merck Announces Positive Topline Results From the First Two Phase 3 CORALreef Trials Evaluating Enlicitide Decanoate for the Treatment of Adults With Hyperlipidemia. 2025. [Press release]. Available at: www.businesswire.com/news/home/20250609545552/en/ (accessed 8 July 2025).
8. ClinicalTrials.gov. A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017) CORALreef HeFH. ClinicalTrials.gov identifier: NCT05952869. Available at: https://clinicaltrials.gov/study/NCT05952869  (accessed 8 July 2025).
9. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Enlicitide Decanoate (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018) CORALreef AddOn. ClinicalTrials.gov identifier: NCT06450366. Available at: https://clinicaltrials.gov/study/NCT06450366 (accessed 8 July 2025).
10. ClinicalTrials.gov. A Research Study to Compare a Medicine Called Semaglutide Against Placebo in People With Peripheral Arterial Disease and Type 2 Diabetes (STRIDE). ClinicalTrials.gov identifier: NCT04560998. Available at: https://clinicaltrials.gov/study/NCT04560998 (accessed 9 July 2025).
11. Verma S. Diabetes and Peripheral Artery Disease—Evolving Role of GLP-1 RA and New Insights from the STRIDE Trial. Presented at: 85th American Diabetes Association Scientific Sessions, Chicago, 21 June, 2025.
12. HCP Live. STRIDE: Semaglutide Reduces Progression of PAD by 54% in Type 2 Diabetes. 2025. [Press release]. Available at: www.hcplive.com/view/stride-semaglutide-reduces-progression-of-pad-by-54-in-type-2-diabetes (accessed 9 July 2025).
13. Keros Therapeutics. Keros Therapeutics Announces TROPOS Topline Data and Corporate Restructuring. 2025.[ Press release]. Available at: https://ir.kerostx.com/news-releases/news-release-details/keros-therapeutics-announces-tropos-topline-data-and-corporate (accessed 9 July 2025).
14. ClinicalTrials.gov. A Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (PAH) (TROPOS Study). ClinicalTrials.gov identifier: NCT05975905. Available at: https://clinicaltrials.gov/study/NCT05975905 (accessed 9 July 2025).

Further content in cardiovascular disease.

Editor: Victoria Smith, Senior Content Editor.

Disclosures: This article was created by the touchCARDIO team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

Cite: June 2025 Cardiology Roundup: Approvals, Trials and Trends. touchCARDIO. 9 July 2025.

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