Zydena (udenafil) / Mezzion - LARVOL DELTA

Targeting Novel Pathways in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of New Therapeutic Agents. (PubMed, Niger Med J) - "Udenafil and fasudil showed modest benefits, while anastrozole had mixed results with possible sex-specific effects. At the individual trial level, sotatercept (0.7 mg/kg), riociguat (2.5 mg), and metformin (500 mg with bosentan) showed the most favourable benefit profiles. Standardised trial designs and consistent outcome reporting are needed to confirm these potential disease-modifying effects."

Journal • Retrospective data • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Transcription factor EN1 governs a lipogenic USP18-ACLY axis to drive bladder cancer malignancy. (PubMed, Oncogene) - "Udenafil suppressed the USP18/ACLY axis and inhibited BLCA progression in preclinical models. This study defines the EN1-USP18-ACLY axis as a master regulator of lipogenesis and a promising therapeutic target in BLCA, supporting the repositioning of Udenafil as a potential treatment strategy."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • USP18

An integrative machine learning and structure-driven drug repositioning strategy for human IRAK4-targeted cancer therapy. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The efficacy of these candidates was further supported by their low toxicity profiles, via graph neural network (GNN)-based toxicity analysis. These findings establish a scalable computational strategy for identifying repurposable oncology therapeutics and propose udenafil, linagliptin, benflumetol, and nimodipine as mechanistically credible candidates for experimental validation."

Journal • Oncology • IRAK4

Spin-labeling studies implicate a highly dynamic active state for transducin-bound phosphodiesterase-6 in vertebrate phototransduction. (PubMed, bioRxiv) - "Binding of Gα T * to PDE6 with the competitive inhibitor udenafil occupying its catalytic sites alters the positions of the PDEγ subunits in agreement with the striking changes shown in the cryoEM structure for this complex, whereas coupling the Gα T * subunits to the bivalent antibody does not affect the DEER distributions observed for PDE6 bound to Gα T *. However, binding of the slow hydrolyzing 8-Br-cGMP substrate in the presence of Gα T * causes a dramatic increase in the separation and spread of the spin-labelled PDEγ subunits, thereby revealing a previously unobserved conformation of PDE6 associated with catalysis. These studies indicate that whereas inhibitors trap Gα T *-PDE6 complexes in an inactive state as represented by the cryoEM structure, the binding of both substrate and Gα T * produces a dynamic active state consistent with an alternating site mechanism."

Journal

Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials. (PubMed, Syst Rev) - "Compared with the placebo, PDE5is improved vascular parameters, indicating the potential of PDE5is for treating subclinical cardiovascular diseases. Further research is needed to confirm the role of the improvement on vascular parameters by PDE5isin preventing and treating cardiovascular diseases."

Journal • Retrospective data • Review • Cardiovascular • Erectile Dysfunction

FUELExten: A Extension Study of Udenafil in Adolescents (clinicaltrials.gov) - P3 | N=301 | Completed | Sponsor: Mezzion Pharma Co. Ltd | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Heart Failure

FALD: Evaluation of Fontan-associated Hepatic Stiffness and the Efficacy of Udenafil in Reducing Liver Stiffness (clinicaltrials.gov) - P3 | N=88 | Completed | Sponsor: Mezzion Pharma Co. Ltd | Phase classification: P ➔ P3

Biomarker • Phase classification • Cardiovascular • Heart Failure

Pharmacological Modulation of Liver and Spleen Stiffness in a Cirrhotic Rat Model. (PubMed, Hepat Med) - "Rats were divided into six groups: control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin, and carvedilol. Terlipressin did not reduce LS or SS, likely due to opposing effects of increased MAP and reduced PVP. In conclusion, combined LS and SS measurements may provide valuable non-invasive insights into patient responses and adherence to PH-lowering therapies."

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

Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial. (PubMed, J Am Heart Assoc) - "In this post hoc subgroup analysis, after exclusion of patients with Fontan circulation with near-normal baseline peak Vo2, a positive treatment effect of udenafil was identified for the primary outcome of peak Vo2. The interaction between baseline peak Vo2 and treatment may have influenced the outcome of the FUEL trial."

Journal • Retrospective data

Parental and adolescent perceptions of clinical trial participation: the FUEL randomised controlled trial and open-label extension study. (PubMed, Cardiol Young) - "Perceptions of research were positive and slightly better for parents. Study teams and compensation were key contributors to positive perceptions. Study burden and testing were viewed less favourably. Future studies should consider families' preferences and potential barriers to participation."

Journal • Cardiovascular • Heart Failure

FALD: Evaluation of Fontan-Associated Liver Disease (clinicaltrials.gov) - P=N/A | N=88 | Completed | Sponsor: Mezzion Pharma Co. Ltd | Active, not recruiting ➔ Completed

Biomarker • Trial completion • Cardiovascular • Heart Failure • Hepatology

Methylated Arginine Metabolites as Biomarkers for Clinical Status and Response to Type 5 Phosphodiesterase Inhibition in Patients With Fontan Circulation. (PubMed, J Am Heart Assoc) - "Plasma concentrations of metabolites that inhibit NO flux are associated with negative clinical outcomes and worse exercise capacity. Moreover, metabolite shifts over time associated with increased NO flux are associated with improved exercise capacity. In patients with a Fontan circulation, the NO pathway modulators ADMA and symmetric dimethyl arginine may be useful as biomarkers of clinical status and predictive of response to PDE5is."

Biomarker • Journal • Cardiovascular • Heart Failure

New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review. (PubMed, Cureus) - "Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat...The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

An overview of conventional and investigational phosphodiesterase 5 inhibitors for treating erectile dysfunction and other conditions. (PubMed, Expert Opin Investig Drugs) - "Pre-clinical and early clinical trials that investigated safety, efficacy and tolerability of novel PDE5I such as Udenafil, Mirodenafil, Lodenafil, Youkenafil, Celecoxib and TPN729 in treatment of ED and other conditions. Preclinical and limited early clinical studies of the new molecules of PDE5I have demonstrated encouraging results however, safety, efficacy, and tolerability are still an issue that necessitate further long-term multicenter clinical studies to ensure justification of their uses in treatment of ED and other conditions.Progress in molecular delivery techniques and tailored patient-specific management and additional therapeutic technology will dramatically improve care for ED and other conditions. The dream of ED and many other conditions becoming more effectively managed may be feasible in the near future."

Journal • Review • Erectile Dysfunction

Nicolau syndrome (embolia cutis medicamentosa) due to glatiramer acetate (Copaxone) injection: a case report (BAD 2024) - "Drug history included glatiramer acetate, levothyroxine, pregabalin, udenafil, propranolol, levetiracetam and docusate...Oral doxycycline 100 mg once daily was started, as a swab showed a heavy growth of Staphylococcus aureus...Conservative treatment with debridement, pain control and dressings are the mainstays of therapy. This case highlights the need for awareness about this rare condition."

Case report • Clinical • Anesthesia • CNS Disorders • Epilepsy • Immunology • Multiple Sclerosis • Pain

Postmicturition dribble in men with no previous urogenital surgery: Systematic review and meta-analysis of treatment modalities. (PubMed, Neurourol Urodyn) - "Physical/behavioral therapy and PDE5 inhibitors are effective primary PMD treatments. PMD management studies in males with no previous urethral/prostatic surgery are very scarce and lack the use of consistent/comparable outcome measures. Further studies addressing these deficiencies would benefit this very thin evidence base."

Journal • Retrospective data • Review • Surgery • Urinary Incontinence • Urology • Women's Health

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation. (PubMed, Am J Cardiol) - "There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration."

Clinical • Journal • Cardiovascular • Heart Failure

FUEL-2: Fontan Udenafil Exercise Longitudinal Assessment Trial - 2 (clinicaltrials.gov) - P3 | N=436 | Recruiting | Sponsor: Mezzion Pharma Co. Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Heart Failure

Phosphodiesterase 5 inhibitors: preclinical and early phase breakthroughs for impotence treatments. (PubMed, Expert Opin Investig Drugs) - "Our review of udenafil, mirodenafil, youkenafil, lodenafil, and SLx-2101 analyzes the safety, efficacy, and pharmacokinetic properties of these new ED drugs. It is our opinion that more robust clinical trials are required before these medications can be made available in the United States. Additionally, the field of urology may benefit from pursuing other avenues of pharmacotherapy, such as injections, tablets with a different mechanism of action, or stem cell therapy, to restore the integrity of the endothelium within the penis."

Journal • Preclinical • Review • Erectile Dysfunction • Urology

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis. (PubMed, Pediatr Cardiol) - P3 | "The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115."

Journal • Pediatrics

FUEL-2: Fontan Udenafil Exercise Longitudinal Assessment Trial - 2 (clinicaltrials.gov) - P3 | N=436 | Not yet recruiting | Sponsor: Mezzion Pharma Co. Ltd

New P3 trial • Cardiovascular • Heart Failure

A pilot study to explore the effect of udenafil on cerebral hemodynamics in older adults. (PubMed, Ann Clin Transl Neurol) - "Our results showed a paradoxical effect of udenafil on cerebral hemodynamics in older adults. This contradicts our hypothesis, but it suggests that fNIRS is sensitive to changes in cerebral hemodynamics in response to PDE5Is."

Journal

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants. (PubMed, Circ Cardiovasc Imaging) - P3 | "FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort."

Journal

Efficacy and Safety of Udenafil Once Daily in Patients with Erectile Dysfunction after Bilateral Nerve-Sparing Robot-Assisted Laparoscopic Radical Prostatectomy: A Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, World J Mens Health) - "Udenafil 75 mg once daily after BNS-RALP improved the erectile function without any severe adverse effects."

Clinical • Journal • Erectile Dysfunction • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Using a quantum dot bead-based lateral flow immunoassay to broadly detect the adulteration of PDE-5 inhibitors in functional foods. (PubMed, Anal Methods) - "For the determination of lodenafil, methisosildenafil, mirodenafil, udenafil and tadalafil, the limit of detection (LOD) and IC ranged from 1.01 to 26.91 ng mL and 12.75 to 278 ng mL, respectively. In addition, the validity and the consistency have been confirmed with a comparison between QB-LFIA and HPLC-MS/MS (R = 0.9957). Furthermore, the developed QB-LFIA was employed for the inspection of real products, and several samples were found to be adulterated with lodenafil and methisosildenafil."

Journal