- |||||||||| Olorofim (orotomide) / Shionogi
Review, Journal: Review of the novel antifungal drug olorofim (F901318). (Pubmed Central) - Nov 15, 2024
It is only orally available and shows very promising results in ongoing clinical trials. In this review we will describe the mechanism of action of olorofim, the spectrum of activity in vitro and in vivo, pharmacokinetics, pharmacodynamics, drug-drug interactions, resistance, and clinical outcomes.
- |||||||||| Review, Journal: Usage of Antifungal Agents in Pediatric Patients Versus Adults: Knowledge and Gaps. (Pubmed Central) - Sep 26, 2024
Despite the promising potential of novel antifungal drugs, their performance in heavily immunosuppressed patients remains unstudied. Until then, dedicated antifungal stewardship programs for high-risk patients are essential to optimize therapeutic outcomes, improve patient care, and limit the emergence of resistance.
- |||||||||| Olorofim (orotomide) / Shionogi, Brexafemme (ibrexafungerp) / SCYNEXIS, GSK, fosmanogepix (APX001) / Basilea
Journal: Antifungal pipeline: Is there light at the end of the tunnel? (Pubmed Central) - Jun 20, 2024
Their future role hinges on thorough clinical validation, cost-effectiveness assessments, and continuous post-marketing surveillance. Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges.
- |||||||||| Olorofim (orotomide) / Shionogi
Trial completion date, Trial primary completion date: OASIS: Olorofim Aspergillus Infection Study (clinicaltrials.gov) - Jun 4, 2024
P3, N=225, Recruiting,
Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges. Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Sep 2024 --> Sep 2025
- |||||||||| Olorofim (orotomide) / Shionogi
Trial completion date: OASIS: Olorofim Aspergillus Infection Study (clinicaltrials.gov) - Apr 17, 2024
P3, N=225, Recruiting,
The moderators will present challenging cases of invasive fungal infections in solid organ transplant recipients, and in these settings, the speakers will discuss the data on novel antifungal therapies. Trial completion date: Mar 2025 --> Nov 2025
- |||||||||| Olorofim (orotomide) / Shionogi
DEFYING DANGER: ASSESSING OLOROFIM'S IMPACT ON THE LIVER - A CASE REPORT OF SEVERE DILI AND SUCCESSFUL RECHALLENGE (Hall A, Poster Hall - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_5902;
He was restarted on Itraconazole...The transient episodes of disorientation were attributed to seizures originating from prior ischemic foci after EEG revealed consistent findings, prompting the initiation of Levetiracetam...Existing preliminary clinical trial data indicate an 8% incidence of DILI possibly linked to Olorofim, yet the severity and specific characteristics of this hepatotoxicity has not been described. Additional research elucidating the severity spectrum, mechanisms, and predisposing factors is crucial for informed clinical decision-making and ensuring patient safety during Olorofim therapy.
- |||||||||| Olorofim (orotomide) / Shionogi
Cost-Effectiveness of Olorofim in Invasive Aspergillosis Patients Lacking Suitable Alternative Treatment Options from a US Payer Perspective () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1861;
P2b
Additional research elucidating the severity spectrum, mechanisms, and predisposing factors is crucial for informed clinical decision-making and ensuring patient safety during Olorofim therapy. Model parameters included healthcare utilization costs in 2023 USD (antifungal agents, ICU days, general ward days, TEAE management), quality-adjusted life years (QALYs) estimated using EQ-5D-5L utilities for success and failure from the P2b study data, and an olorofim proxy price the same as that of liposomal amphotericin B. One-way (OWSA) and probabilistic sensitivity analyses (PSA) were performed to test the model
- |||||||||| Journal: Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective. (Pubmed Central) - Feb 28, 2024
The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed.
- |||||||||| Olorofim (orotomide) / F2G
Journal: Anti-Aspergillus activities of olorofim at sub-MIC levels during early-stage growth. (Pubmed Central) - Feb 5, 2024
Compared to standardized, less-sensitive visual assessment-based methods, microscopy-assisted growth monitoring allowed us to detect sub-MIC drug concentration ranges with significant inhibitory activity at early-stage growth. This revealed that olorofim exerts growth inhibition at concentrations that are several magnitudes below those of voriconazole.
- |||||||||| Olorofim (orotomide) / F2G
Review, Journal: Accelerating the understanding of Aspergillus terreus: Epidemiology, physiology, immunology and advances. (Pubmed Central) - Feb 2, 2024
The exploration of epidemiology, morphological transitions, immunopathology, and novel treatment approaches such as new antifungal drugs (PC945, olorofim) and combinational therapy using antifungal drugs and phytochemicals (Phytochemicals: quercetin, shikonin, artemisinin), also using immunotherapies to modulate immune response has resulted in better outcomes...This is attributed to the use of immune-suppressing therapies during COVID-19 infections and the increase in transplant cases. Consequently, this review aims to provide an updated overview encompassing the epidemiology, germination events, immunopathology, and novel drug treatment strategies against Aspergillus terreus-associated infections.
- |||||||||| Olorofim (orotomide) / Shionogi, Mycamine (micafungin) / Astellas, Noxafil (posaconazole) / Merck (MSD)
INFECTIOUS ORIGINS OF PULMONARY HYPERTENSION AND RIGHT VENTRICULAR FAILURE: MILIARY COCCIDIOIDOMYCOSIS UNVEILED (Moderated Poster Theater 10) - Jan 26, 2024 - Abstract #ACC2024ACC_4006;
The pathogenesis is hypothesized to involve hematogenous obstruction of capillary vessels, resulting in increased pulmonary pressures. This pathophysiology of occlusion of the distal pulmonary vasculature falls under group 4 PH, typically linked with chronic thromboembolic PH.
- |||||||||| Rezzayo (rezafungin for injection) / Cidara Therap, Mundipharma, Melinta Therap, Olorofim (orotomide) / F2G, Noxafil (posaconazole) / Merck (MSD)
Review, Journal: High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies. (Pubmed Central) - Jan 23, 2024
The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug-drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs' risk stratification), and new antifungals and their features (rezafungin and olorofim).
- |||||||||| Review, Journal: Update on therapeutic approaches for invasive fungal infections in adults. (Pubmed Central) - Jan 22, 2024
We discuss management of complex infections with specific emerging fungi such as Scedosporium spp., Fusarium spp., Trichosporon asahii, and Candida auris. We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.
- |||||||||| Nulojix (belatacept) / BMS
Scedosporium Brain Abscess in a Lung Transplant Recipient Treated with Belatacept (Poster Hall) - Jan 9, 2024 - Abstract #ISHLT2024ISHLT_1528;
The patient was treated with intravenous voriconazole and neuroembolization on POD 87. Olorofim, obtained through compassionate use, was added for persistently positive cultures and worsening clinical condition on POD 142...On POD 185, comfort care was initiated upon the family
- |||||||||| Review, Journal: Antifungal resistance, combinations and pipeline: oh my! (Pubmed Central) - Nov 29, 2023
Fosmanogepix, ibrexafungerp, olorofim and rezafungin may help fill some of these gaps in the antifungal armamentarium. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.
- |||||||||| Olorofim (orotomide) / F2G
Journal: Refractory Microascus Bronchopulmonary Infection Treated with Olorofim, France. (Pubmed Central) - Oct 29, 2023
bronchopulmonary infection in a multiple-traumatized patient and 2 lung transplant recipients in France. We emphasize the promising use of olorofim antifungal therapy in a rising context of intrinsically less-susceptible respiratory infections caused by mold.
- |||||||||| Review, Journal: Treatment of Invasive Aspergillosis: How It's Going, Where It's Heading. (Pubmed Central) - Oct 23, 2023
Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA.
- |||||||||| Olorofim (orotomide) / F2G, Cresemba (isavuconazonium sulfate) / Astellas, Basilea, Pfizer, Laboratoire Riva, Asahi Kasei
A Case Study: Recurrent Invasive Rhinocerebral Aspergillosis (Monitor 07) - Sep 14, 2023 - Abstract #ACAAI2023ACAAI_666;
After a 6-month hospitalization, he was discharged on oral voriconazole but had difficulties with adherence due to gastrointestinal side effects...After treatment with neurosurgery and IV antifungals, he was transitioned to isavuconazole and referred to our immunology clinic for further workup...He has since been placed on the investigational antifungal Olorofim and is undergoing additional studies to detect impairments in his polymorphonuclear cells and antifungal neutralization capacity...In mouse models, neutralization of CXCR2 activity resulted in the development of invasive pulmonary aspergillosis. At this time, there are few studies characterizing human phenotypes associated with CXCR2 mutations.
- |||||||||| Olorofim (orotomide) / F2G
Journal: Characterisation of putative class 1A DHODH-like proteins from Mucorales and dematiaceous mould species. (Pubmed Central) - Aug 6, 2023
However, further experimental investigation of the putative class 1A-like genes through yeast complementation and biochemical assays characterised them as dihydrouracil oxidases rather than DHODHs. These data demonstrate variation in dematiaceous mould olorofim susceptibility is not due to a secondary DHODH and builds on the growing picture of fungal dihydrouracil oxidases as an example of horizontal gene transfer.
- |||||||||| Rezzayo (rezafungin for injection) / Cidara Therap, Mundipharma, Melinta Therap, Olorofim (orotomide) / F2G, Brexafemme (ibrexafungerp) / SCYNEXIS
Journal: Novel Antifungals and Aspergillus Section Terrei with Potpourri Susceptibility Profiles to Conventional Antifungals. (Pubmed Central) - Jun 27, 2023
In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All the antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus as well as azole-resistant and AmB-non-wildtype cryptic species.
- |||||||||| Review, Journal: Aspergillosis: an Update on Clinical Spectrum, Diagnostic Schemes, and Management. (Pubmed Central) - Jun 26, 2023
The fungus Aspergillus is found ubiquitously around the world and can cause various infections, from harmless saprophytic colonization to severe IA. Understanding the diagnostic criteria to be used in different patient groups and the local epidemiological data and antifungal susceptibility profile is critical for optimal patient management.
- |||||||||| Olorofim (orotomide) / F2G, Noxafil (posaconazole) / Merck (MSD)
Journal: Genotyping and antifungal susceptibility testing of Sporothrix brasiliensis isolates from Southern Brazil. (Pubmed Central) - Jun 5, 2023
The novel antifungal olorofim exhibited excellent activity against this large isolate collection, with all isolates considered as susceptible. Altogether, we indicate zoonotic transmission based on genotyping and revealed a broad activity of seven common antifungals, including olorofim, against a large S.?brasiliensis isolate collection.
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