Vasa Therapeutics reports NT-proBNP reduction with VS-041 after 28 days in a Phase 1c HFpEF trial, evaluating MMP inhibition and biomarker-guided patient selection.
Written By: Mayuri Vaja, PharmD
Reviewed By: Pharmacally Editorial Team
Vasa Therapeutics has announced positive topline results from a randomized, placebo-controlled Phase 1c trial evaluating VS-041 in patients with heart failure with preserved ejection fraction (HFpEF). The investigational oral therapy demonstrated a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) following 28 days of treatment, providing an initial clinical proof-of-concept signal for its therapeutic approach.
The study, registered as VS-041-102 (NCT07219511), planned to enrol 42 participants across 21 clinical sites in the United States. Participants received one of two dose levels of VS-041 or placebo while continuing background guideline-directed medical therapy. The company reported that treatment was safe and well tolerated at both dose levels.
However, the announcement did not disclose the exact doses, administration schedule, magnitude of NT-proBNP reduction or dose-specific treatment responses. The extent of the biomarker effect therefore remains difficult to assess independently.
VS-041 Demonstrates Reduction in NT-proBNP
The reduction in NT-proBNP represents the principal clinical finding from the Phase 1c study. NT-proBNP is an established biomarker associated with cardiac wall stress and heart failure and is widely used in cardiovascular disease assessment.
Although the reported reduction provides an early indication of biological activity, it does not independently establish improvements in cardiac function, exercise capacity, symptoms or hospitalization risk. The absence of quantitative results and detailed statistical analyses also limits assessment of the treatment effect.
The study’s 28-day treatment period and relatively small planned enrolment are consistent with an early-stage safety and biomarker-focused investigation rather than a definitive efficacy assessment.
Targeting Myocardial Fibrosis and Matrix Remodeling
VS-041 is an oral, narrow-spectrum small-molecule inhibitor of matrix metalloproteinases (MMPs), designed to target fibroinflammation and abnormal extracellular matrix (ECM) turnover in the myocardium.
The therapeutic rationale involves the role of MMP activity in extracellular matrix remodeling and fibrotic processes associated with myocardial stiffening and impaired relaxation. These mechanisms contribute to the development and progression of HFpEF.
In preclinical HFpEF models, VS-041 demonstrated reductions in cardiac fibrosis and improvements in diastolic function. The compound was also reported to be safe and well tolerated at doses consistent with preclinical efficacy in an earlier Phase 1 study involving healthy participants.
These findings provide the biological rationale for its clinical development. However, improvements in cardiac fibrosis and diastolic function have not yet been demonstrated in treated human patients.
Biomarker-Guided Patient Selection
An important aspect of the Phase 1c study was the prospective use of elevated serum endotrophin levels to identify an HFpEF subgroup associated with fibroinflammation.
Endotrophin, a collagen VI-derived peptide associated with extracellular matrix remodeling and fibrotic processes, was measured using the NordicProC6 assay. The strategy aimed to identify patients with a more homogeneous disease phenotype based on underlying biological characteristics.
This approach addresses an important challenge in HFpEF development: the condition involves multiple underlying mechanisms, making treatment response difficult to assess across an unselected patient population.
By identifying patients with evidence of fibroinflammation, Vasa aims to align the treatment’s proposed mechanism with the underlying disease biology. The company believes this enrichment strategy could support smaller and potentially faster future clinical studies.
Further analyses of exploratory clinical measures and biomarkers associated with fibroinflammation and collagen turnover are expected in early 2027. The company has not specified individual exploratory clinical endpoints in its topline announcement.
Regulatory Status and Development Outlook
The US Food and Drug Administration granted VS-041 Fast Track Designation in November 2025, supporting its development for HFpEF.
Beyond heart failure, Vasa is exploring the potential of VS-041 in other chronic conditions characterized by fibroinflammatory processes, including hypertrophic cardiomyopathy and chronic kidney disease. These remain potential applications rather than established clinical indications.
HFpEF: Persistent Unmet Needs Despite Available Therapies
HFpEF is a complex form of heart failure characterized by myocardial stiffness and impaired relaxation despite preserved contractile function. Vasa estimates that the condition affects approximately three million people in the United States and 10 million globally.
Current HFpEF management includes sodium-glucose cotransporter-2 (SGLT2) inhibitors such as empagliflozin and dapagliflozin, alongside diuretics and management of associated comorbidities. Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide, have also demonstrated benefits in patients with obesity-related HFpEF, particularly in symptoms, physical limitations and weight reduction.
Nevertheless, opportunities remain for treatments targeting underlying myocardial structural changes and fibrotic processes.
VS-041’s Phase 1c findings provide an initial human clinical signal for an approach targeting MMP activity and abnormal matrix remodeling. Its combination of mechanism-directed treatment and endotrophin-based patient enrichment represents a potentially important development strategy in a heterogeneous disease.
However, the limited duration, small planned study population and absence of detailed numerical results prevent conclusions about clinical efficacy or disease modification. The forthcoming biomarker and exploratory clinical analyses will be important in determining whether the observed NT-proBNP reduction supports progression into subsequent clinical studies.
Reference
Vasa Therapeutics Announces Positive Topline Results from Randomized, Placebo-Controlled Phase 1c Trial of VS-041 for Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF), Vasa Therapeutics, 12 November 2026
A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants with Heart Failure with Preserved Ejection Fraction (HFpEF), ClinicalTrials.gov ID NCT07219511
About the Writer
Mayuri Vaja (Linkedin) is a Pharm.D professional with a strong interest in clinical research, pharmacovigilance, and medical writing, supported by certifications in pharmacovigilance and academic projects exploring AI in healthcare and drug safety.
With a growing focus on evidence-based healthcare and scientific communication, she is developing expertise in clinical research and translating healthcare evidence into clear, meaningful content.
As a Pharmacally healthcare writer, Mayuri is committed to creating accurate, research-driven, and clinically relevant healthcare content while continuously strengthening her professional skills.