avenciguat (BI 685509) / Boehringer Ingelheim - LARVOL DELTA

Pharmacokinetics of novel drugs for the treatment of Diabetic nephropathy. (PubMed, Expert Opin Drug Metab Toxicol) - "Evidence was synthesized for sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dual incretin agonists, nonsteroidal mineralocorticoid receptor antagonists (nsMRA), endothelin receptor antagonists (ERA), aldosterone synthase inhibitors (vicadrostat, baxdrostat, and lorundrostat), avenciguat, and ziltivekimab, emphasizing exposure, clearance, metabolism, elimination, and dosing implications. In reduced kidney function, SGLT2i show modest exposure increases but attenuated glucose-lowering effects, finerenone shows modest exposure increases despite minimal renal clearance, and ERA may have larger increases that narrow the therapeutic window. Newer incretin therapies generally maintain stable exposure, while eGFR alone may incompletely capture PK risk because uremia, altered protein binding, and nonrenal clearance can influence exposure. The next advance is likely to be drug-specific decision support integrating estimated..."

Journal • PK/PD data • Review • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

avenciguat: EU/3/24/2989 - orphan designation for treatment of systemic sclerosis (European Medicines Agency) - "Please note that this product was withdrawn from the Union Register of orphan medicinal products in April 2026 on request of the Sponsor."

European regulatory • Systemic Sclerosis

Renal safety and albuminuria evolution with soluble ganylate cyclase stimulation: real-world evidence with vericiguat in advanced cardiorenal disease. (ERA 2026) - "This is especially relevant in view of ongoing clinical development of next generation sGC stimulators such as avenciguat...The mediam left ventricular ejection fraction was 35% (29-39) At baseline, 92% were receiving sacubitril–valsartan, 89% a mineralocorticoid receptor antagonist, 95% SGLT2 inhibitor and 10% a GLP-1 receptor agonist...Baseline and follow-up data. Image"

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Hypertension • Hypotension • Inflammation • Metabolic Disorders • Nephrology • Renal Disease

Results of a Phase II study (VITALISScE) with the soluble guanylate cyclase activator avenciguat (EULAR 2026) - "There were consistent improvements in all RP symptoms, including major Raynaud’s outcomes such as number and duration of attacks, Raynaud’s Condition Score, patient assessment, clinician assessment, pain, numbness and tingling (Fig 1B) but no difference in the number of patients with new DUs (30 patients in each arm). Conclusions While treatment with avenciguat was well tolerated and led to consistent improvement in RP symptoms, there was no evidence of effects on DUs, or on lung and skin fibrosis."

P2 data • Cardiovascular • Constipation • Dyspepsia • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hypotension • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • CRP

A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms (clinicaltrials.gov) - P2 | N=214 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Immunology • Scleroderma • Systemic Sclerosis • CRP

Mass balance and absolute bioavailability of avenciguat (14C) after intravenous or oral administration in healthy male participants. (PubMed, Expert Opin Investig Drugs) - P1 | "After oral administration, avenciguat has high oral bioavailability. ClinicalTrials.gov (NCT05515328)."

Journal • Chronic Kidney Disease • Immunology • Nephrology • Renal Disease • Scleroderma • Systemic Sclerosis

Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed. (PubMed, J Clin Med) - "(5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent...Many novel agents-many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)-are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms (clinicaltrials.gov) - P2 | N=188 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Nov 2025 ➔ Feb 2026

Trial completion date • Immunology • Scleroderma • Systemic Sclerosis • CRP

Nephrology: What You May Have Missed in 2024. (PubMed, Ann Intern Med) - "Three studies examined treatments to improve specific aspects of CKD management, including mineralocorticoid receptor agonists to address heart failure, avenciguat to address albuminuria, and oral phosphate binders to address fracture risk. One study demonstrated that inorganic nitrate reduced the risk for contrast-induced nephropathy. Finally, a trial of cefepime-taniborbactam showed benefit for treating complicated urinary tract infection."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Infectious Disease • Musculoskeletal Diseases • Nephrology • Orthopedics • Renal Calculi • Renal Disease

Registry Clinical Trials on Treatment of Cirrhotic Portal Hypertension Evaluated by Hepatic Venous Pressure Gradient: A Systematic Review (APASL 2025) - " Drug Classification by Pharmacological Mechanism: Beta-blockers (30%): Including carvedilol and propranolol, targeting portal pressure reduction. Vasodilators (15%): Agents like doxazosin and nitrates targeting vascular resistance. Anti-metabolic agents (10%): Metformin targeting hepatic insulin sensitivity. Gut microbiota modulators (10%): Rifaximin and probiotics improving gut-liver interactions. Experimental agents (15%): Emerging therapies such as BI 685509... This systematic review underscores the diversity in therapeutic strategies for CPH, with beta-blockers as the mainstay of treatment and promising new directions from emerging agents. Despite progress, variability in trial phases and limited long-term follow-up necessitate larger, harmonized trials across all phases to refine HVPG-guided therapies for CPH. Table and Figure:Figure 1.Regional Distribution of Clinical Trials Figure 2.Focus Areas of Primary Outcomes in Clinical Trials"

Clinical • Review • Cardiovascular • Hepatology • Portal Hypertension

Avenciguat: a novel soluble guanylate cyclase activator that affects multiple cell types to inhibit IFN-1 signalling and fibrosis. (PubMed, Rheumatology (Oxford)) - P2 | "In preclinical studies, avenciguat shows the potential to influence vascular, fibrotic and immune-related processes in murine models of SSc. These studies suggest that it may offer therapeutic benefit across multiple aspects of SSc pathophysiology and support the rationale for further investigation in a Phase II clinical trial (VITALISScE™; NCT05559580) of avenciguat in SSc."

Journal • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • TGFB1

A novel soluble guanylate cyclase activator, avenciguat, in combination with empagliflozin, protects against renal and hepatic injury in diabetic db/db mice. (PubMed, Am J Physiol Endocrinol Metab) - "These results suggested that either avenciguat alone or in combination with Empa is therapeutic. Avenciguat in combination with Empa shows promise in halting the progression of diabetic complications."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Fibrosis • Genetic Disorders • Glomerulonephritis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms (clinicaltrials.gov) - P2 | N=188 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Scleroderma • Systemic Sclerosis • CRP

A Phase II study of avenciguat, a novel soluble guanylate cyclase activator, in patients with systemic sclerosis: Study design and rationale of the VITALISScE™ study. (PubMed, J Scleroderma Relat Disord) - P2 | "VITALISScE™; EU CT No. 2022-500332-11-00; Clinicaltrials.gov: NCT05559580 (https://www.clinicaltrials.gov/study/NCT05559580)."

Journal • P2 data • Cardiovascular • Fibrosis • Immunology • Rheumatology • Scleroderma • Systemic Sclerosis

A Study to Test How Avenciguat (BI 685509) is Taken up in the Body of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Boehringer Ingelheim | N=16 ➔ 4 | Recruiting ➔ Terminated; Sponsor decision

Enrollment change • Trial termination • Hepatology

Avenciguat reduces albuminuria in patients with chronic kidney disease. (PubMed, Nat Rev Nephrol) - No abstract available

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

A Study to Test Whether BI 685509 Alone or in Combination With Empagliflozin Helps People With Liver Cirrhosis Caused by Viral Hepatitis or Non-alcoholic Steatohepatitis (NASH) Who Have High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver) (clinicaltrials.gov) - P2 | N=90 | Terminated | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Terminated; Company decision

Combination therapy • Trial termination • Cardiovascular • Fibrosis • Gastroenterology • Hepatology • Hypertension • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Portal Hypertension

A Study to Test Whether Two Different Doses of Avenciguat Help People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Live (clinicaltrials.gov) - P2 | N=80 | Terminated | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Terminated; Company decision

Trial termination • Cardiovascular • Fibrosis • Gastroenterology • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension

A Study to Test Whether Avenciguat Helps People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver) Who Had Bleeding in the Esophagus or Fluid Accumulation in the Belly (clinicaltrials.gov) - P2 | N=22 | Terminated | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Terminated; Company decision

Trial termination • Cardiovascular • Fibrosis • Gastroenterology • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension

Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh a cirrhosis detected by an oral cholate challenge test. (PubMed, Liver Transpl) - P1 | "The results support further study of avenciguat in treating portal hypertension and spotlight the utility of HepQuant DuO in the development of drug therapy for liver disease. HepQuant DuO facilitates use of function testing to measure hepatic improvement in clinical trials and the clinic."

Journal • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension

A Study to Test Whether Two Different Doses of Avenciguat Help People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Live (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2024 ➔ Jun 2024 | Trial primary completion date: Sep 2024 ➔ Jun 2024

Trial completion date • Trial primary completion date • Cardiovascular • Fibrosis • Gastroenterology • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension

Efficacy and safety of avenciguat in diabetic and non-diabetic kidney disease: Pooled analysis from two Phase II randomised controlled clinical trials (ERA-EDTA 2024) - P2 | "Avenciguat was effective in lowering albuminuria and was well tolerated in patients with diabetic and non-diabetic CKD. These results will support avenciguat dose selection for future trials."

Late-breaking abstract • P2 data • Retrospective data • Chronic Kidney Disease • Diabetic Nephropathy • Hypotension • Nephrology • Renal Disease

Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials. (PubMed, J Am Soc Nephrol) - P2 | "Avenciguat lowered albuminuria, and was well tolerated in patients with CKD."

Clinical • Journal • Chronic Kidney Disease • Metabolic Disorders • Renal Disease

Safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 685509, a soluble guanylyl cyclase activator, in healthy volunteers: Results from two randomized controlled trials. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - P1 | "Increased plasma cyclic guanosine monophosphate and decreased blood pressure followed by a compensatory increase in heart rate indicated target engagement. BI 685509 was generally well tolerated; orthostatic dysregulation may be appropriately countered by careful uptitration."

Journal • PK/PD data • Fatigue

A Study to Test Whether Avenciguat Helps People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver) Who Had Bleeding in the Esophagus or Fluid Accumulation in the Belly (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | N=40 ➔ 22

Enrollment change • Enrollment closed • Cardiovascular • Fibrosis • Gastroenterology • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension