otesaconazole (VT-1161) / Mycovia Pharma, Jiangsu Hengrui Pharma - LARVOL DELTA

Cost-Effectiveness Analysis of Oteseconazole vs. Fluconazole for Patients With Severe Vulvovaginal Candidiasis in China (ISPOR-EU 2025) - "As the main clinical inputs in the model, clinical cure rate and recurrence rate were derived from the Chinese clinical trial SHR8008-302 and the international clinical trial VMT-VT-1161-CL-004, respectively. Compared to fluconazole, oteseconazole was a more cost-effective choice for patients with severe VVC in China."

Clinical • Cost effectiveness • HEOR • Candidiasis • Vaginitis

Sustained Efficacy of Oteseconazole in Women with Recurrent Vulvovaginal Candidiasis. (PubMed, J Womens Health (Larchmt)) - "The proportion of participants who prematurely discontinued the study was lower in the oteseconazole-treated group (16%) compared with the placebo group (29%). During the 48-week extension study, 1.4% of previously randomized subjects experienced a culture-positive recurrence of symptomatic vulvovaginal candidiasis, demonstrating a continued long-term protective effect of oteseconazole."

Journal • Candidiasis • Infectious Disease • Vaginitis

Oteseconazole in the Treatment of Adults With Vulvovaginal Candidiasis（VVC） (clinicaltrials.gov) - P=N/A | N=3000 | Not yet recruiting | Sponsor: Beijing Tsinghua Chang Gung Hospital

New trial • Real-world evidence • Candidiasis • Vaginitis

Azole resistance: insights from Y132 substitutions in Candida sterol 14α-demethylase utilizing molecular dynamics simulations. (PubMed, J Biomol Struct Dyn) - "Extensive molecular dynamics simulations of sterol 14α-demethylase bound to fluconazole or VT1161 (VT1) were performed using GROMACS, and the ligand-binding free energies were computed to quantify the effects of various Y132 substitutions on azole binding/interactions. Far higher binding free energy of fluconazole in comparison with VT1 might partly explain its susceptibility to azole-resistant substitutions. The results give key insights into azole resistance, and antifungal drug discovery and optimization."

Journal • Candidiasis • Infectious Disease

Synthesis, X-Ray Structure, Characterization, Antifungal Activity, DFT, and Molecular Simulation of a Novel Pyrazole Carboxylic Acid. (PubMed, Curr Top Med Chem) - "The results suggest that compound L1 is a promising antifungal candidate, showing greater potential than fluconazole in the conducted evaluations. Further studies are warranted to explore its full therapeutic potential."

Journal

The Molecular Basis of the Intrinsic and Acquired Resistance to Azole Antifungals in Aspergillus fumigatus. (PubMed, J Fungi (Basel)) - "A crowded conformationally sensitive region involving the BC-loop, helix I, and the heme makes AfCYP51A T289 primarily responsible for resistance to fluconazole, VT-1161, and the agrochemical difenoconazole. The Y121F T289A combination was required for higher level acquired resistance to fluconazole, VT-1161, difenoconazole, and voriconazole, and confirms posaconazole, isavuconazole and possibly ravuconazole as preferred treatments for target-based azole-resistant aspergillosis due to such a combination of mutations."

Journal • Preclinical • Pulmonary Disease • Respiratory Diseases

Ecotoxicity and Mutagenicity Assessment of Novel Antifungal Agents VT-1161 and T-2307. (PubMed, Molecules) - "Despite these favorable results, further research is needed to understand their environmental behavior, interactions, and potential resistance development among non-target species. Our findings highlight the importance of comprehensive environmental risk assessments to ensure the sustainable use of new antifungal agents."

Journal • CNS Disorders • Infectious Disease • Psychiatry

Identification of Potent and Selective Inhibitors of Acanthamoeba: Structural Insights into Sterol 14α-Demethylase as a Key Drug Target. (PubMed, J Med Chem) - "The strongest inhibition was observed with voriconazole (1 h IC50 0.45 μM), VT1598 (0.25 μM), and VT1161 (0.20 μM). The crystal structures of A. castellanii CYP51 with bound VT1161 (2.24 Å) and without an inhibitor (1.95 Å), presented here, can be used in the development of azole-based scaffolds to achieve optimal amoebicidal effectiveness."

Journal • CNS Disorders • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology

Cost-Effectiveness Analysis of Oteseconazole Versus Fluconazole for Patients With Severe Vulvovaginal Candidiasis in China (ISPOR 2024) - "As the main clinical inputs in the model, clinical cure rate and recurrence rate were devied from the Chinese clinical trial SHR8008-302 and the international clinical trial VMT-VT-1161-CL-004, respectively. Compared to fluconazole, oteseconazole was a more cost-effective choice for patients with severe VVC in China."

Clinical • Cost effectiveness • HEOR • Candidiasis • Vaginitis

A Preliminary Evaluation on the Antifungal Efficacy of VT-1161 against Persister Candida albicans Cells in Vulvovaginal Candidiasis. (PubMed, Biomedicines) - "Antifungal activity was determined by the minimum inhibitory concentration (MIC), and the primary biofilm was treated with amphotericin B to obtain persister cells that were able to form a new biofilm. Results obtained using the new azole VT-1161 showed that VT-1161 not only eradicated a secondary biofilm formed from the persister-derived biofilm and counteracted the adhesion of C. albicans in vitro to human cells but also ameliorated C. albicans-induced infection in vivo in Galleria mellonella larvae, suggesting that it could be proposed as an alternative therapeutic strategy for the treatment of recurrent candidiasis."

Journal • Candidiasis • Infectious Disease • Vaginitis

"Efficacy and safety of oteseconazole in recurrent vulvovaginal candidiasis (RVVC) - A systematic review and meta-analysis". (PubMed, Heliyon) - "Although standard guidelines recommend oral and topical fluconazole as its treatment regimen, approval of another drug Oteseconazole has drawn the attention because of its better safety profile and lower recurrence rate by its use. The purpose of our Meta-analysis is to evaluate the safety and efficacy of Oteseconazole (Vivjoa) (VT-1161) in the treatment of Recurrent Vulvovaginal Candidiasis (RVVC)...The available evidence suggests Oteseconazole to be safer and more efficacious. However, limited patient population points towards the need of further large and dedicated trials for definitive conclusion."

Journal • Retrospective data • Review • Candidiasis • Infectious Disease • Vaginitis

Oteseconazole for the Treatment of Recurrent Vulvovaginal Candidiasis: A Drug Review. (PubMed, Ann Pharmacother) - "Search terms included "oteseconazole" OR "VT-1161" or "VIVJOA" AND "RVVC" or "recurrent vulvovaginal candidiasis" or "vulvovaginal candidiasis." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review...Oteseconazole is an effective and safe treatment option for the management of RVVC though current research lacks comparison with established maintenance regimens. Additional research is needed to ascertain the placement of oteseconazole in the treatment of RVVC."

Journal • Review • Candidiasis • Vaginitis

Oteseconazole: a long-awaited diversification of the antifungal arsenal to manage recurrent vulvovaginal candidiasis (RVVC). (PubMed, Expert Rev Anti Infect Ther) - "For decades, maintenance treatment using the azole antifungal fluconazole was the preferred treatment...Oteseconazole (VT-1161), marketed as VIVJOA, is an oral, tetrazole antifungal with unprecedented specificity toward the fungal lanosterol 14α-demethylase...Further, the availability and cost may, like for most novel drugs, affect the widespread clinical implementation of VIVJOA. Altogether, we are convinced that VIVJOA is a significant advance in RVVC management."

Journal • Review • Candidiasis • Vaginitis

An extensive review on antifungal approaches in the treatment of mucormycosis. (PubMed, J Biochem Mol Toxicol) - "Amphotericin B (1) and isavuconazole (2) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole (3) and deferasirox (4) is another approach for patients who are not responsible for any other therapy...There are some drugs like VT-1161 (5) and APX001A (6), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

Benzo[g]quinazolines as antifungal against candidiasis: Screening, molecular docking, and QSAR investigations. (PubMed, Saudi Pharm J) - "CYP51 to establish the binding mode compared with fluconazole and VT-1161 (oteseconazole) as reference medicines, and it was determined that binding at the active site of Candida spp. Quantitative structure-activity relationship (QSAR) investigation was performed to further characterize the identified anticandidal agents and recognize the major regulatory components governing such activity. In future studies, the benzo[g]quinazoline scaffold could serve as a model for the design and development of novel derivatives with antifungal potential."

Journal • Candidiasis • Infectious Disease

Functional Expression of Recombinant Candida auris Proteins in Saccharomyces cerevisiae Enables Azole Susceptibility Evaluation and Drug Discovery. (PubMed, J Fungi (Basel)) - "Phenotypes were evaluated for standard azoles and the tetrazole VT-1161. Overexpression of CauErg11 Y132F, CauErg11 K143R, and CauMdr1 conferred resistance exclusively to the short-tailed azoles Fluconazole and Voriconazole...CauCdr1 exhibited ATPase activity that was inhibited by Oligomycin. The S. cerevisiae overexpression platform enables evaluation of the interaction of existing and novel azole drugs with their primary target CauErg11 and their susceptibility to drug efflux."

Journal • Candidiasis • Infectious Disease • ABCB1

VT-1161-A Tetrazole for Management of Mono- and Dual-Species Biofilms. (PubMed, Microorganisms) - "Since long-term therapy is necessary for most fungal biofilm infections due to their recurrence and obstinacy, VT-1161 showed low cytotoxicity against normal human cell lines and also against the invertebrate model Caenorhabditis elegans. Considering the excellent anti-biofilm potential and its GRAS (generally recognized as safe) status, VT-1161 may find use in the prevention or therapeutic treatment of mono- or poly-microbial biofilms."

Journal • Infectious Disease • Pneumonia

Phase 3 Study of the Safety and Efficacy of Oteseconazole in Treatment of Recurrent Vulvovaginal Candidiasis and Efficacy vs Fluconazole in Treatment of Acute Vulvovaginal Candidiasis Infections. (PubMed, Am J Obstet Gynecol) - "In participants with RVVC, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute VVC episodes and was noninferior to VVC standard-of-care fluconazole in the treatment of the presenting acute VVC infection."

Journal • P3 data • Candidiasis • Infectious Disease • Vaginitis

Invasive candidiasis: Investigational drugs in the clinical development pipeline and mechanisms of action. (PubMed, Expert Opin Investig Drugs) - "Insights are offered on the potential future roles of the investigational agents MAT-2203, oteseconazole, ATI-2307, VL-2397, NP-339, and the repurposed drug miltefosine. Ibrexafungerp and fosmanogepix have novel mechanisms of action and will provide effective options for the treatment of Candida infections (including those caused by multiresistant Candida spp). Rezafungin, an echinocandin with an extended half-life allowing for once weekly administration, will be particularly valuable for outpatient treatment and prophylaxis. Despite this, there is an urgent need to garner clinical data on investigational drugs, especially in the current rise of azole-resistant and multi-drug resistant Candida spp."

Journal • Candidiasis • Infectious Disease

Future Fungal Fighters in Dermatology: Novel Antifungal Drug Pipeline. (PubMed, J Drugs Dermatol) - "Novel drugs in the pipeline include ME1111, MAT2203, rezafungin, ibrexafungerp, olorofim, fosmanogepix, MGCD290, VT-1161, NP213, T-2307, aureobasidin A, and nikkomycin Z. While most of these “future fungal fighters” have been developed to address invasive fungal infections (IFI), there is potential for dermatologists to benefit as these drugs may be adapted for superficial infections. 2022;21(5):496-501. doi:10.36849/JDD.6373."

Journal • Dermatology • Infectious Disease

Novel antifungal agents in clinical trials. (PubMed, F1000Res) - "Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics.  The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics.  This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim.  We examine three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties."

Journal • Review • Infectious Disease

Characterisation of Candida parapsilosis CYP51 as a Drug Target Using Saccharomyces cerevisiae as Host. (PubMed, J Fungi (Basel)) - "Constitutive expression of CpCYP51 Y132F conferred a 10- to 12-fold resistance to fluconazole and voriconazole, reduced to ~6-fold resistance for the tetrazoles VT-1161 and VT-1129, but did not confer resistance to the long-tailed triazoles. We report the X-ray crystal structure of ScCYP51 in complex with VT-1129 obtained at a resolution of 2.1 Å. Structural analysis of azole-enzyme interactions and functional studies of recombinant CYP51 from C. parapsilosis have improved understanding of their susceptibility to azole drugs and will help advance structure-directed antifungal discovery."

Journal • Candidiasis • Infectious Disease

VIOLET: A Study of Oral Oteseconazole for the Treatment of Patients With Recurrent Vaginal Candidiasis (Yeast Infection) (clinicaltrials.gov) - P3; N=438; Completed; Sponsor: Mycovia Pharmaceuticals Inc.; N=326 ➔ 438

Clinical • Enrollment change • Candidiasis • Infectious Disease • Vaginitis

Investigational antifungal agents for invasive mycoses: a clinical perspective. (PubMed, Clin Infect Dis) - "These include new drugs within the existing antifungal classes or displaying similar mechanism of activity with improved pharmacologic properties (rezafungin, ibrexafungerp) or first-in-class drugs with novel mechanisms of action (olorofim, fosmanogepix). Although critical information regarding the performance of these agents in heavily immunosuppressed patients is pending, they may provide useful additions to current therapies in some clinical scenarios, including IFI caused by azole-resistant Aspergillus or multi-resistant fungal pathogens (e.g. Candida auris, Lomentospora prolificans). However, their limited activity against Mucorales and some other opportunistic molds (e.g. some Fusarium spp.) persists as a major unmet need."

Clinical • Journal • Dermatology • Infectious Disease

Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, oteseconazole. (PubMed, Int J Dermatol) - "We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented."

Journal • Review • Infectious Disease