Reasanz (serelaxin) / Novartis - LARVOL DELTA

Long-acting relaxin analogues: a novel tool in cardiology. (PubMed, Front Pharmacol) - P1 | "In this article, we provide an overview of the mechanisms underlying the effects of long-acting relaxin analogues and their positive impact on the cardiovascular system. Additionally, we present a comprehensive comparison between serelaxin and its novel analogues, exploring their potential implications for the future treatment of cardiovascular diseases."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

Clinical Presentation, Biomarker Trajectories, and Outcomes in Women and Men Hospitalized for Acute Heart Failure. (PubMed, JACC Heart Fail) - P3 | "During an AHF hospitalization, women received lower doses of loop diuretic agents and achieved less weight loss with slightly lower diuretic response compared with men, despite similar symptom relief and postdischarge outcomes. Early incident WRF was more frequent in women and was associated with worse 180-day outcomes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)."

Biomarker • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

Clinical profiles and prognostic impact of residual intravascular and tissue congestion in acute heart failure (HEART FAILURE 2025) - " Congested patients from two large AHF trials, PROTECT (Rolofylline; derivation) and RELAX-AHF2 (Serelaxin; validation), were classified based on clinical signs at day 7/discharge into intravascular (jugular venous pressure), tissue (pulmonary rales/peripheral oedema), or a combined congestion phenotype... Residual intravascular congestion is most common among those with RC at discharge. These patients had a good diuretic response with lower diuretic dosages and a shorter hospital stay than those with residual tissue/combined congestion, but worse outcomes than patients without RC. This suggests that better decongestion at discharge may particularly be achieved in patients with residual intravascular congestion."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Relaxin-2 Ameliorates Spinal Cord Injury by Inhibiting Microglia Activation. (PubMed, Kaohsiung J Med Sci) - "Furthermore, continuous subcutaneous infusion of Serelaxin (0.5 mg/kg/day; human recombinant relaxin-2) improved neurological recovery, as evidenced by higher Basso-Beattie-Bresnahan (BBB) scores and reduced foot-stepping angles compared to the SCI group...It also inhibited the activation of the NF-κB signaling and strengthened the activation of the STAT6 signaling in the spinal cord of SCI mice. These findings suggest that RLN-2 may be a promising therapeutic agent for the treatment of spinal cord injury."

Journal • CNS Disorders • Inflammation • Orthopedics • AQP4 • CAT • IL6 • STAT6 • TNFA

End-organ protective effect of serelaxin in patients hospitalized for heart failure: Results of the biomarker substudy of Relaxin in Acute Heart Failure-2 (RELAX-AHF-2). (PubMed, Eur J Heart Fail) - "In this substudy, serelaxin decreased plasma concentrations of cardiac, renal and hepatic injury markers. Changes of most of these markers were associated with cardiovascular mortality. In this pre-specified biomarker subgroup, serelaxin did not reduce 180-day cardiovascular mortality but significantly reduced worsening heart failure through day 5."

Biomarker • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hepatology • Liver Failure • CST3

Decongestion and Outcomes in Patients Hospitalized for Acute Heart Failure: Insights From the RELAX-AHF-2 Trial. (PubMed, JACC Heart Fail) - P3 | "Among patients with AHF who were still hospitalized at day 5, residual congestion was common and independently associated with worse outcome. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

Relaxin agonists under preclinical and early clinical investigation for the treatment of heart failure. (PubMed, Expert Opin Investig Drugs) - "However, there has been mixed evidence from clinical trials involving relaxin which could be due to patient groups, investigation sites, trial design and chance. Further studies should focus on developing biomarkers to identify specific population groups who are most likely to benefit from relaxin."

Journal • Preclinical • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

Impact of age on clinical outcomes and response to serelaxin in patients with acute heart failure: An analysis from the RELAX-AHF-2 trial. (PubMed, Eur J Heart Fail) - "Elderly patients are at higher risk of short- and long-term CV outcomes after a hospitalization for AHF. Further efforts are needed to improve CV outcomes in this population."

Clinical • Clinical data • Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Renal Disease

Clinical Management of Primary Aldosteronism: An Update. (PubMed, Hypertension) - "Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Atherothrombosis Intervention in High-Risk Patients Using Serelaxin), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available."

Journal • Review • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Hematological Disorders • Hypertension • Myocardial Infarction • Nephrology • Pulmonary Arterial Hypertension • Renal Disease • Thrombosis

Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2. (PubMed, JACC Heart Fail) - "Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF."

Journal • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

New Pharmacotherapeutic Classes for the Management of Heart Failure: A Narrative Review. (PubMed, Cureus) - "We focus on vericiguat, omecamtiv mecarbil, ularitide, and serelaxin, and thoroughly examine their efficacy and safety profiles while summarizing the clinical trials of the drugs. There is a need for more long-term studies comparing the efficacy of these medications to the conventional ones."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue. (PubMed, Biochem Pharmacol) - "Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders."

Journal • Preclinical • Cardiovascular • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • Oncology • CD36 • IL1B • SCARB1 • TNFA

Serelaxin Protects H9c2 Cardiac Myoblasts against Hypoxia and Reoxygenation-Induced Damage through Activation of AMP Kinase/Sirtuin1: Further Insight into the Molecular Mechanisms of the Cardioprotection of This Hormone. (PubMed, Antioxidants (Basel)) - "The inhibition of SIRT1 signaling with EX527 (10 µmol L-1) reduced the beneficial effect of the hormone on mitochondrial efficiency and cell apoptosis. These results strengthen the concept that RLX exerts its cardioprotective effects against H/R-induced injury through multiple pathways which also include AMPK/SIRT1. These new findings support the use of RLX or RLX-derived molecules as a promising therapeutic for those diseases in which I/R and oxidative stress play a pathogenic role."

Journal • Cardiovascular • Reperfusion Injury • SIRT1

R2R01: A long-acting single-chain peptide agonist of RXFP1 for renal and cardiovascular diseases. (PubMed, Br J Pharmacol) - "R2R01 is a potent RXFP1 agonist with an extended half-life that increases renal blood flow in various settings including normotensive and hypertensive conditions. The preclinical efficacy and safety data supported clinical development of R2R01 as a potential new therapy for renal and cardiovascular diseases."

Journal • Allergy • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease • CD4

Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date. (PubMed, J Cardiovasc Dev Dis) - "A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Nephrology • Renal Disease • FGF23

Presentation, clinical course and outcomes of women and men hospitalized with acute heart failure: insights from RELAX-AHF 2 trial (HEART FAILURE 2023) - "Purpose We sought to characterize the clinical phenotype, patient journey, and outcome of men and women with AHF enrolled in a large contemporary, multinational AHF trial, RELAX-AHF 2, the second seRELAXin in Acute Heart Failure trial...During hospital stay, women received lower doses of loop diuretics (120 vs 160 mg furosemide equivalent total intravenous cumulative diuretic dose through day 5, and 243 versus 280 mg furosemide equivalent total oral cumulative diuretic dose through day 5, both p 0.1) as compared to men...However, early incident WRF was more frequent in women and was associated with worse clinical outcomes, that were not observed in men or in women with no WRF through day 5. More studies are warranted to investigate sex differences in renal outcomes in AHF."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • CST3

Cardiovascular effects of relaxin-2: therapeutic potential and future perspectives. (PubMed, Clin Res Cardiol) - "However, evidence from past clinical trials has been inconsistent and further research is needed to fully understand the potential applications of relaxin-2. This review provides an overview of serelaxin use in clinical trials and discusses future directions in the development of relaxin-2 mimetics, which may offer new therapeutic options for patients with heart failure."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation

Serelaxin inhibits LPS-induced inflammatory response in cardiac fibroblasts by activating PPAR-γ and suppressing NF-κB signaling pathway. (PubMed, J Cardiovasc Pharmacol) - "Further studies showed that serelaxin did not significantly increase the expression of PPAR-γ mRNA and protein, but activated PPAR-γ activity, and the PPAR-γ inhibitor GW9662 reversed the inhibitory effect of serelaxin on IL-1β, IL-6, and TNF-α production. These results suggest that serelaxin alleviates cardiac fibrosis by stimulating PPAR-γ via a ligand-independent mechanism which subsequently abolish the expression of NF-κB signalling pathway."

Journal • Fibrosis • Immunology • Inflammation • IL10 • IL1B • IL6 • MMP2 • MMP9 • NFKBIA • PPARA • TNFA

Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway. (PubMed, Int J Mol Sci) - "Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1."

Journal • Fibrosis • Immunology • Infectious Disease • Ophthalmology • Thyroid Eye Disease

Development of a Long-Acting Relaxin Analog, LY3540378, for Treatment of Chronic Heart Failure. (PubMed, Br J Pharmacol) - "LY3540378 demonstrated to be a suitable clinical development candidate and is progressing in clinical trials."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure. (PubMed, Clin Res Cardiol) - "Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Renal Disease

Porcine Relaxin but Not Serelaxin Shows Residual Bioactivity after In Vitro Simulated Intestinal Digestion-Clues for the Development of New Relaxin Peptide Agonists Suitable for Oral Delivery. (PubMed, Int J Mol Sci) - "HPLC analysis indicates that this bioactivity could be ascribed to a minor component of the pRLX sample more resistant to proteolysis. When identified and better characterized, this peptide could be exploited for the development of synthetic relaxin agonists suitable for oral formulations."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Targeted Protein Degradation

Simultaneous late-gadolinium enhancement and T1 mapping of fibrosis and a novel cell-based combination therapy in hypertensive mice. (PubMed, Biomed Pharmacother) - "This study thus, determined whether the anti-fibrotic drug, serelaxin (RLX), could enhance the therapeutic effects of BM-MSCs or BM-MSC-derived exosomes (BM-MSC-EXO) in hypertensive mice...On day 14 post-injury, subgroups of 1 K/DOCA/salt-hypertensive mice were treated with RLX alone or in combination with BM-MSCs or BM-MSC-EXO; or the mineralocorticoid receptor antagonist, spironolactone...It was concluded that the MP2RAGE sequence enhanced the non-invasive CMRI detection of LV fibrosis. Furthermore, combining RLX and BM-MSCs may represent a promising treatment option for hypertensive cardiorenal syndrome."

Combination therapy • Journal • Preclinical • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Nephrology • Transplantation

In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions. (PubMed, Int J Impot Res) - "NO-dependent relaxation responses were evaluated by cumulative acetylcholine (10-10M) administration in the presence of indomethacin (10M). Prostacyclin-mediated relaxation was evaluated by cumulative administration of iloprost (10-10M), a prostacyclin analog...Serelaxin exerts different effects via different mechanism on endothelium-dependent responses depending on the dose and duration of exposure. Therefore, proper timing and dosing of serelaxin administration in the penile tissue need to be investigated in further studies in diabetic animal models."

Journal • Preclinical • Cardiovascular • Coronary Artery Disease • Diabetes • Metabolic Disorders

Optimization of an Ex-Vivo Human Skin/Vein Model for Long-Term Wound Healing Studies: Ground Preparatory Activities for the 'Suture in Space' Experiment Onboard the International Space Station. (PubMed, Int J Mol Sci) - "We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation...As a further clue about cell viability, some typical events associated with wound repair were observed in the tissue areas close to the wound, namely remodeling of collagen fibers in the papillary dermis and of elastic fibers in the vein wall, proliferation of keratinocyte stem cells, and expression of the endothelial functional markers eNOS and FGF-2. These findings validate the suitability of this new ex vivo organ culture system for wound healing studies, not only for the scheduled space experiment but also for applications on Earth, such as drug discovery purposes."

Journal • Preclinical • Transplantation • FGF2 • NOS3