July 2025 cardiovascular breakthroughs: approvals, trial results, and regulatory highlights

Regulatory news

• Pulsed field ablation systems granted expanded indication by FDA for persistent AF

The FDA granted expanded labelling approval for a pulsed field ablation (PFA) system to include treatment of drug-refractory, symptomatic persistent atrial fibrillation (AF).¹ Persistent AF, characterized by abnormal heart rhythms lasting at least seven days, affects a substantial portion of the estimated 59 million individuals living with AF globally. The system uses pulsed field energy to ablate cardiac tissue via catheter, offering a non-thermal option for AF treatment.

This regulatory decision was based on results from phase one of the ADVANTAGE AF trial (NCT05443594), a prospective, single-arm study involving 260 patients intolerant to at least one class I or III anti-arrhythmic drug.^2,3 Conducted across 43 international sites, the trial met its primary safety and efficacy endpoints. No serious complications such as stroke, pulmonary vein stenosis, or atrio-oesophageal fistula were reported. At one year, the symptomatic AF recurrence-free rate was 85.3%, rising to 91.4% among those who had completed at least three procedures.

A new clinical trial, ReMATCH (NCT06735534), is underway to further evaluate the system in patients with recurrent AF, who have had previous ablations and experienced a recurrence of AF.⁴

• FDA approves finerenone for heart failure with left ventricular ejection fraction of ≥ 40%

The FDA approved finerenone, a non-steroidal, selective mineralocorticoid receptor antagonist, for the treatment of adults with heart failure and a left ventricular ejection fraction (LVEF) of 40% or greater.⁵ The approval was supported by the pivotal phase III FINEARTS-HF trial (NCT04435626), a randomized, double-blind, placebo-controlled study.

The study enrolled approximately 6,000 patients with symptomatic heart failure (New York Heart Association class II–IV).^6,7 Participants had an LVEF ≥40% and were receiving diuretic therapy for at least 30 days prior to randomization. Finerenone demonstrated a statistically significant reduction in the composite endpoint of cardiovascular death and total heart failure events, including first and recurrent hospitalizations and urgent visits for heart failure. These benefits were observed across subgroups regardless of comorbidities or background therapy. Finerenone showed a consistent safety profile with studies in other indications, with a higher occurrence than placebo of hyperkalemia (9.7% vs 4.2%), hypotension (7.6% vs 4.7%), hyponatremia (1.9% vs 0.9%), and renal issues (18% vs 12%).

• Regenerative Medicine Advanced Therapy designation granted by FDA for RP A601

The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to RP A601, an investigational adeno-associated virus (AAV)-based gene therapy for the treatment of plakophilin-2 (PKP2)-associated arrhythmogenic cardiomyopathy (ACM).⁸ This genetic condition is characterized by ventricular arrhythmias, progressive heart failure, and sudden cardiac death.

The RMAT designation was supported by preliminary data from the ongoing phase I clinical trial of RP A601, which was presented at the 2025 Annual Meeting of the American Society of Gene and Cell Therapy.⁹ In this study, three adult patients received a single intravenous dose of RP A601 (8×10¹³ GC/Kg). All demonstrated increased expression of PKP2 protein and improved desmosomal integrity. There were improvements or stabilization across clinically meaningful endpoints including right ventricular function, arrhythmia burden, and quality of life. RP A601 was well-tolerated, with no dose-limiting toxicities reported and adverse events limited to mild or moderate intensity.

RMAT designation provides RP A601 with benefits including expedited development, early FDA engagement, and eligibility for accelerated approval pathways.

• FDA grants priority review for sotatercept-csrk to update label following ZENITH trial

The FDA granted priority review to a supplemental Biologics License Application (sBLA) for sotatercept-csrk, seeking to update the product label based on data from the phase III ZENITH trial (NCT04896008).¹⁰ The current indication for sotatercept-csrk includes treatment of adults with pulmonary arterial hypertension (PAH, Group 1). The FDA has set a target action date of October 25, 2025.

The ZENITH trial was a global, double-blind, placebo-controlled phase III study evaluating sotatercept-csrk in patients with advanced PAH at high risk of mortality.¹¹ The trial was stopped early due to overwhelming efficacy. Sotatercept-csrk demonstrated a 76% reduction in the risk of a composite endpoint of all-cause death, lung transplantation, or PAH-related hospitalization ≥24 hours compared to placebo. The safety profile was consistent with prior studies.

If approved, the label update would incorporate these outcome-based data, marking the first PAH phase III study to use a primary endpoint consisting solely of major morbidity and mortality events.

Trial data

• Baxdrostat meets key endpoints in topline data from the BaxHTN trial

A phase III trial evaluating baxdrostat (NCT06034743), a selective aldosterone synthase inhibitor, in patients with uncontrolled or treatment-resistant hypertension met its primary and all secondary endpoints.^12,13 Both 1mg and 2mg doses significantly reduced mean seated systolic blood pressure at 12 weeks compared to placebo. The results support a potential regulatory submission for this novel antihypertensive approach targeting aldosterone dysregulation.