LAmB-FAST is a factorial randomized controlled trial simultaneously testing two interventions in one trial. LAmB-FAST seeks to inform treatment guidelines on the induction and maintenance therapy of HIV-associated talaromycosis (formerly called penicilliosis) and will answer the following three questions:
1. Is induction therapy using a single 10 mg/kg dose of liposomal amphotericin B (LAmB) is more effective than 14 days of the conventional deoxycholate amphotericin B (DAmB)?
2. Is adding flucytosine (5FC) to amphotericin B more effective than amphotericin B alone?
3. Is HIV viral load guided stopping of itraconazole maintenance therapy as effective as the current CD4 guided strategy in the prevention of talaromycosis relapse?

Start Date06 Jan 2025

Sponsor / Collaborator

Duke University

[+6]

NCT06414512 / CompletedPhase 2IIT

Optimizing the Dose of Flucytosine for the Treatment of Cryptococcal Meningitis

Cryptococcal meningitis (CM) is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in Africa where the ongoing HIV/AIDS pandemic leads to higher prevalence of cryptococcosis. Combination of amphotericin and flucytosine (5-FC) is the mainstay of therapy for the initial management of CM. Indeed, it has even been shown that effective delivery of these therapies in Africa can lower mortality rates by 90%.
This is a prospective open-label trial to compare the efficacy and safety of lower doses of 5FC during induction therapy to historical controls with standard 5FC dosing. Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed. Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received. Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days. The intervention group received single- dose liposomal amphotericin plus 5-FC and fluconazole 1200 mg/day.
All participants will receive fluconazole 1200mg/day during consolidation therapy from day 1 to 14 then 800mg/day from day 15 to 10 weeks, and 200mg/day after 10 weeks. All participants will receive lumbar punctures at diagnosis, day 3, day 5-7, day 10-14, and additionally as required for control of intracranial pressure and documentation of CSF sterilization. Controls from Ambition will be matched for the same LP windows. Therapeutic LPs conducted during the first week have a
70% relative survival benefit.

Start Date09 Apr 2024

Sponsor / Collaborator

University of Minnesota

ISRCTN18180872 / RecruitingPhase 2IIT

Population-pharmacokinetics, safety and tolerability of sustained-release flucytosine pellets for the treatment of asymptomatic cryptococcal antigen-positive individuals: a single-arm trial

Start Date15 Jan 2024

Sponsor / Collaborator

Wits Health Consortium

100 Clinical Results associated with Flucytosine

100 Translational Medicine associated with Flucytosine

100 Patents (Medical) associated with Flucytosine

3,867

Literatures (Medical) associated with Flucytosine

04 Dec 2024·AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

Multi-Locus Sequence Typing–Based Genetic Analysis, Antifungal Resistance, and Clinical Prognosis of Cryptococcus neoformans Infections in HIV-Infected Patients in Northern China

Article

Author: Dai, Fang-Fang ; Yu, Yan-Hua ; Lu, Xin-Xin

ABSTRACT.:

This study aimed to investigate the molecular epidemiological characteristics and drug sensitivity of Cryptococcus from HIV-infected patients and their relationship with patients’ prognosis. Seventy-six strains were collected and identified to the species level by matrix-assisted laser desorption ionization–time of flight mass spectrometry, confirmed by internal transcribed spacer sequencing. Multi-locus sequence typing was used for the typing of Cryptococcus, and its antifungal susceptibility was tested using FUNGUS 3. The clinical outcomes of the patients were reviewed at 3-, 6-, 9-, and 12-month follow-ups. All strains were Cryptococcus neoformans var. grubii classified into seven sequence types (STs) dominated by ST5, ST31, and a new ST702 strain. The 6- and 9-month survival rates were highest for patients infected with ST31, ST32, and ST174. The antifungal resistant rates were 13.2%, 2.6%, and 1.4% for fluconazole, amphotericin B, and 5-fluorocytosine. Except itraconazole, the minimum inhibitory concentration (MIC) values and wild type (WT)/non–wild type (NWT) of Cryptococcus for antifungal drugs were not related to the clinical prognosis of HIV-infected patients with cryptococcal infection. ST5 was the main ST type, and the new ST702 type was found in a patient who died in a short period of time. Cryptococcus neoformans var. grubii had a relatively high antifungal drug resistance rate to fluconazole. The WT strain accounted for the highest proportions for 5-fluorocytosine, amphotericin B, fluconazole, voriconazole, and itraconazole. The MIC values of Cryptococcus for first-line antifungal drugs showed no relationship with clinical prognosis, implying that MIC values cannot be used to predict the clinical outcome of these patients.

01 Dec 2024·INTERNATIONAL IMMUNOPHARMACOLOGY

The potential of mesenchymal stem cell coexpressing cytosine deaminase and secretory IL18-FC chimeric cytokine in suppressing glioblastoma recurrence

Article

Author: Korourian, Alireza ; Taheri, Mojtaba ; Arefian, Ehsan ; Ramezani, Mohammad ; Farzad, Sara Amel ; Tehrani, Hossein Abdul

Glioblastoma multiforme (GBM) patients have a high recurrence rate of 90%, and the 5-year survival rate is only about 5%. Cytosine deaminase (CDA)/5-fluorocytosine (5-FC) gene therapy is a promising glioma treatment as 5-FC can cross the blood-brain barrier (BBB), while 5-fluorouracil (5-FU) cannot. Furthermore, 5-FU can assist reversing the immunological status of cold solid tumors. This study developed mesenchymal stem cells (MSCs) co-expressing yeast CDA and the secretory IL18-FC superkine to prevent recurrent tumor progression by simultaneously exerting cytotoxic effects and enhancing immune responses. IL18 was fused with Igk and IgG2a FC domains to enhance its secretion and serum half-life. The study confirmed the expression and activity of the CDA enzyme, as well as the expression, secretion, and activity of secretory IL18 and IL18-FC superkine, which were expressed by lentiviruses transduced-MSCs. In the transwell tumor-tropism assay, it was observed that the genetically modified MSCs retained their selective tumor-tropism ability following transduction. CDA-expressing MSCs, in the presence of 5-FC (200 µg/ml), induced cell cycle arrest and apoptosis in glioma cells through bystander effects in an indirect transwell co-culture system. They reduced the viability of the direct co-culture system when they constituted only 12.5 % of the cell population. The effectiveness of engineered MSCs in suppressing tumor progression was assessed by intracerebral administration of a lethal dose of GL261 cells combined in a ratio of 1:1 with MSCs expressing CDA, or CDA and sIL18, or CDA and sIL18-FC, into C57BL/6 mice. PET scan showed no conspicuous tumor mass in the MSC-CDA-sIL18-FC group that received 5-FC treatment. The pathological analysis showed that tumor progression suppressed in this group until 20th day after cell inoculation. Cytokine assessment showed that both interferon-gamma (IFN-γ) and interleukin-4 (IL-4) increased in the serum of MSC-CDA-sIL18 and MSC-CDA-sIL18-FC, treated with normal saline (NS) compared to those of the control group. The MSC-CDA-sIL18-FC group that received 5-FC treatment showed reduced serum levels of IL-6 and a considerably improved survival rate compared to the control group. Therefore, MSCs co-expressing yeast CDA and secretory IL18-FC, with tumor tropism capability, may serve as a supplementary approach to standard GBM treatment to effectively inhibit tumor progression and prevent recurrence.

01 Dec 2024·PEDIATRIC INFECTIOUS DISEASE JOURNAL

An Unusual High Prevalence of Cryptococcus (Naganishia) diffluens Colonization in Neonates Hospitalized in a Referral Neonatal Intensive Care Unit

Article

Author: Rezai, Mohammad Sadegh ; Ghazanfari, Mona ; Javidnia, Javad ; Tavakoli, Mahin ; Hedayati, Mohammad Taghi ; Abastabar, Mahdi ; Mayahi, Sabah ; Ashrafi Khozani, Mahtab ; Roilides, Emmanuel ; Haghani, Iman ; Moazeni, Maryam ; Farhadi, Roya ; Yazdani Charati, Jamshid

Background::

Although the Candida species continue to be the most frequent colonizer of neonatal skin, a clear increase of colonization due to rare yeast-like fungi has been reported. In this study, we report an unusual high prevalence of Cryptococcus diffluens colonization in neonates admitted to the neonatal intensive care unit (NICU) over a 1-month period.

Methods::

From January 2020 to June 2021, the study included all neonates who were admitted to the NICU of Bu Ali Sina Hospital at least 28 days old. Skin swabs from different anatomical areas were collected. Sampling was done 3 times/week. Each sample was inoculated into Sabouraud Dextrose Agar containing chloramphenicol and CHROMagar Candida, separately. The plates were incubated at 30 °C and 35 °C, respectively. Identification of the isolates was molecularly confirmed. In vitro antifungal susceptibility testing of the isolates was performed against different antifungal agents using the Clinical Laboratory Standards Institute protocol.

Results::

Among 1026 samples collected from 78 neonates, 213 yeast isolates were recovered, of which the Candida species were the most common (77.5%), followed by C. diffluens (16.9%). During the study, 55 isolated yeasts were collected from December 26, 2020, to January 26, 2021, of which 65.5% were C. diffluens, while Candida spp. constituted 100% and 98.3% of the isolates before and after this period, respectively. The most frequent sources of C. diffluens were genital regions (27.8%). Of 36 C. diffluens isolates, 13.9%, 22.2%, 52.8%, and 83.3% were non-wild type to fluconazole, amphotericin B, itraconazole and 5-flucytosine, respectively.

Conclusions::

We reported for the first time an unusual high prevalence of C. diffluens colonization in neonates hospitalized in NICU. Our findings also showed the high minimum inhibitory concentration of amphotericin B and 5-flucytosine against C. diffluens.

News (Medical) associated with Flucytosine

30 Apr 2024

·www.prnewswire.com

CIRM Awards $11.8 Million Grant for Clinical Trial in High-Grade Glioma Including Glioblastoma Using DB107, a Novel DGM7™ Genetic Biomarker-Guided Gene Therapy

SAN DIEGO, April 30, 2024 /PRNewswire/ -- Denovo Biopharma LLC (Denovo), a pioneer in applying precision medicine to the development of innovative therapies, today announced that the California Institute for Regenerative Medicine (CIRM) has awarded a $11.8M grant for further development of DB107, Denovo's DGM7™ biomarker–guided late–stage gene therapy, for high–grade glioma (HGG) including glioblastoma (GBM), a malignant brain cancer. CIRM has awarded the grant to Dr. Noriyuki Kasahara, MD, PhD, at the University of California San Francisco (UCSF) and a group of investigators at California universities to conduct a Phase 1/2 clinical trial studying DB107 in patients with newly–diagnosed HGG. Continue Reading The trial, titled "A Phase I/IIa Study to Evaluate the Efficacy of DB107–RRV, Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination with DB107–FC and Radiation Therapy or DB107–FC, Temozolomide (TMZ) and Radiation Therapy in Patients with Newly–Diagnosed High–Grade Glioma," plans to enroll up to 70 patients. The trial aims to demonstrate improvements in progression–free survival. We are thrilled to continue the clinical development of our biomarker-guided DB107 gene therapy in HGG including GBM. Post this DB107 consists of two components: DB107–RRV (vocimagene amiretrorepvec) as a prodrug activator gene therapy and DB107–FC (extended-release 5–fluorocytosine [5–FC]) as an oral prodrug. DB107–RRV, a retroviral replicating vector (RRV) administered intratumorally and intravenously, converts the orally administered 5–FC into the potent chemotherapy agent 5–fluorouracil (5–FU) locally at the tumor sites. This enables intratumoral concentrations 30–50 times of those achievable by 5–FU systemic administration, killing tumor cells while minimizing the systemic exposure and off–target toxicities of 5–FU. Using its proprietary biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI), Denovo discovered the novel germline genetic biomarker, Denovo Genomic Marker 7 (DGM7), which is located in the SHROOM3 gene intron. Retrospective analysis of an earlier randomized clinical trial in patients with recurrent HGG suggested improved overall survival in DGM7–positive patients treated with DB107. "We are excited to conduct this novel trial which will be investigating several new approaches for the first time in patients with newly–diagnosed high–grade glioma. In addition to DB107–RRV being administered both intratumorally and intravenously to provide more exposure, this study will also use the RRV in conjunction with radiation therapy and chemotherapy with temozolomide. In addition to the direct therapeutic effect of gene therapy, glioma cells will be sensitized to these standard therapies by 5–FU generated directly within the patient's tumor from DB107–FC. We are also excited to test the DGM7 biomarker to see if we can identify patients who may benefit the most from this unique gene therapy approach," said Dr. Kasahara. DGM7 status will be determined at the time of enrollment to prospectively assess the effect of the biomarker on clinical outcomes. The study will be conducted at UCSF (Dr. Noriyuki Kasahara, MD, PhD, and Dr. Nicholas Butowski, MD), University of Southern California (USC) (Dr. Thomas Chen, MD, PhD), and University of California San Diego (UCSD) (Dr. David Piccioni, MD, PhD), and will be managed by Anova Enterprises, Inc. "We are thrilled to continue the clinical development of our biomarker–guided DB107 gene therapy in patients with HGG including GBM, a major unmet medical need with less than 5% of GBM patients surviving 5 years," said Dr. Matthew A. Spear, MD, Denovo's Chief Medical Officer and Chief Development Officer. "Alongside our recent announcement of positive results in a Phase 2b clinical trial of our DGM4 biomarker–guided DB104 drug (liafensine) in treatment–resistant depression, the CIRM grant provides continued validation of Denovo's approach to discovering new genetic biomarkers and developing biomarker–guided therapies." About HGG and GBM The most common type of high–grade glioma (HGG) is glioblastoma (GBM), which is also the most common type of adult primary brain cancer, with 18,000 newly–diagnosed patients in the US and 13,000 deaths annually. Standard treatments for patients with newly–diagnosed GBM can include surgery followed by radiation and chemotherapy, but treatment options are limited. The 5–year survival rate of patients with GBM is less than 5%. About DB107 and the DGM7™ Biomarker DB107 is an investigational combination product consisting of the DB107–RRV (vocimagene amiretrorepvec) gene therapy and DB107–FC (extended–release 5–fluorocytosine) oral prodrug. DB107–RRV, an innovative proprietary retroviral replicating vector (RRV), is combined with DB107–FC to selectively infect and kill cancer cells while stimulating a robust and durable anti–cancer immune response against a tumor with minimal toxicity. DB107 has been tested clinically in solid tumors including recurrent high–grade glioma (rHGG) and colorectal cancer, most recently in a randomized 403–patient Phase 2/3 trial in rHGG including glioblastoma (GBM). Using its proprietary biomarker discovery platform, Denovo discovered the novel genetic biomarker, DGM7, which has been shown to be associated with treatment response to DB107 in patients with rHGG including GBM. DB107 has received Fast Track Designation and Breakthrough Therapy Designation from the FDA, as well as Orphan Drug Designations from the FDA and EMA. About Denovo Biopharma Denovo Biopharma LLC (Denovo) is a clinical–stage biopharmaceutical company that uses a novel biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI) to find new genetic biomarkers predictive of drug efficacy, and then uses these biomarkers to execute efficient clinical trials in targeted patient populations to increase the probability of success. Denovo has eight late–stage drugs in its pipeline addressing major unmet medical needs in oncology and central nervous system diseases; most of the pipeline are first–in–class drugs with global rights. Denovo recently announced a major breakthrough in treatment–resistant depression (TRD) with its DGM4™ biomarker–guided DB104 drug (liafensine, a potential first–in–class triple reuptake inhibitor for TRD). The global Phase 2b clinical trial of DB104 in DGM4–positive patients with TRD demonstrated strikingly positive results, with highly significant improvements in symptoms of depression seen in DGM4–positive patients. Visit for additional information. Contact Michael F. Haller, Chief Business Officer Denovo Biopharma LLC [email protected] SOURCE Denovo Biopharma LLC

Phase 2Orphan DrugFast TrackClinical ResultGene Therapy

22 Aug 2023

·www.biospace.com

Matinas BioPharma Announces Publication of Results from the Phase 2 EnACT Clinical Trial of MAT2203 in the IDSA Journal Clinical Infectious Diseases

BEDMINSTER, N.J., Aug. 22, 2023 (GLOBE NEWSWIRE) -- Matinas BioPharma (NYSE American: MTNB), a clinical-stage biopharmaceutical company focused on delivering groundbreaking therapies using its lipid nanocrystal (LNC) platform delivery technology, announces that University of Minnesota Medical School researchers published results from the Phase 2 EnACT trial evaluating MAT2203 for the treatment of cryptococcal meningitis as a Major Article and Editor’s Choice in Clinical Infectious Diseases, an official publication of the Infectious Diseases Society of America (IDSA). MAT2203 is an oral and non-toxic, LNC formulation of the potent antifungal drug amphotericin B. David Boulware, MD, MPH, the senior investigator of the EnACT trial and infectious disease physician at the University of Minnesota, commented, “An orally administered amphotericin that is broad spectrum and non-toxic sounds like the holy grail of antifungal medicines. While further clinical trials are needed in other fungal conditions, the EnACT trial establishes proof of concept for the safe and effective treatment of invasive fungal infections. In this randomized trial of 141 HIV-positive individuals afflicted by life-threatening cryptococcal meningitis, the oral amphotericin MAT2203 product combined with oral flucytosine appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than intravenous amphotericin B. With six weeks of LNC-enabled oral amphotericin B, statistically fewer lab abnormalities occurred than with one week of intravenous amphotericin B.” “We are very pleased that the important EnACT data are being shared with the clinical and scientific community at large through publication in this peer-reviewed journal,” said Theresa Matkovits, Ph.D., and Chief Development Officer of Matinas. “The results from EnACT in cryptococcal meningitis and our experience with patients enrolled in our Compassionate/Expanded Use Access Program support our belief that MAT2203 has the potential to become an important part of the regimen for treatment of invasive fungal infections, including in the highest-need patients who require longer-term treatment and have limited or no treatment options. The publication of the EnACT data in Clinical Infectious Diseases is yet another milestone for our development program. We would like to thank all the EnACT participants, our dedicated investigators, and the entire clinical study team in Uganda for their commitment to this important clinical trial.” About the EnACT Phase 2 Study EnACT was a Phase 2 prospective, randomized, open-label, sequential cohort study, financially supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH), evaluating the safety, tolerability, and efficacy of MAT2203 in 100 HIV-positive persons with cryptococcal meningitis compared to 41 persons randomized to receive standard of care intravenous amphotericin B. The EnACT trial included a total of four cohorts of participants, with the first two cohorts testing MAT2203 as early step-down therapy following initial treatment with IV amphotericin B during the induction period, and the second two cohorts testing MAT2203 as potentially all oral therapy. Cohorts 1 and 3 were safety lead-ins to Cohorts 2 and 4, respectively. The induction period for all patients in each cohort (active or control) was 14 days, followed by an additional four weeks of treatment (active or control) during a consolidation/maintenance period. About Clinical Infectious Diseases (CID) Clinical Infectious Diseases (CID) is a leading journal in the field of infectious disease with a broad international readership. The Journal publishes articles on a variety of subjects of interest to practitioners and researchers. Topics range from clinical descriptions of infections, public health, microbiology, and immunology to the prevention of infection, the evaluation of current and novel treatments, and the promotion of optimal practices for diagnosis and treatment. Clinical Infectious Diseases is an official publication of the Infectious Diseases Society of America and is among the most highly cited journals in the field of infectious diseases. About Matinas BioPharma Matinas BioPharma is a biopharmaceutical company focused on delivering groundbreaking therapies using its lipid nanocrystal (LNC) platform delivery technology. Matinas’ lead LNC-based therapy is MAT2203, an oral formulation of the broad-spectrum antifungal drug amphotericin B, which although highly potent, can be associated with significant toxicity. Matinas’ LNC platform provides oral delivery of amphotericin B without the significant nephrotoxicity otherwise associated with IV-delivered formulations. MAT2203 also allows for safe, longer-term use outside of a hospital setting, which could have substantial favorable pharmacoeconomic impact. MAT2203 successfully completed the Phase 2 EnACT program in cryptococcal meningitis, meeting its primary endpoint and achieving robust survival. MAT2203 is being positioned for a single pivotal Phase 3 study in the treatment of aspergillosis and other invasive fungal infections, including mucormycosis, Candida auris and other candidiasis, and certain endemic fungal infections in persons with limited treatment options who are unable to be treated with azoles or echinocandins for reasons related to drug-drug interactions, resistance or for whom these antifungal agents are unable to be used for other clinical reasons. In addition to MAT2203, preclinical and clinical data have demonstrated that this novel technology can provide solutions to many of the challenges standing in the way of achieving safe and effective intracellular delivery of both small molecules and larger, more complex molecular cargos such as RNAi, antisense oligonucleotides, and vaccines. The combination of its unique mechanism of action and flexibility with routes of administration (including oral) positions Matinas’ LNC technology to potentially become a preferred next-generation intracellular drug delivery platform. For more information, please visit . Forward-looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including those relating to our business activities, our strategy and plans, our collaboration with National Resilience, Inc., the potential of our LNC platform and PS-NP delivery technologies, and the future development of its product candidates, including MAT2203, the Company’s ability to identify and pursue development, licensing and partnership opportunities for its products, including MAT2203, or platform delivery technologies on favorable terms, if at all, and the ability to obtain required regulatory approval and other statements that are predictive in nature, that depend upon or refer to future events or conditions. All statements other than statements of historical fact are statements that could be forward-looking statements. Forward-looking statements include words such as "expects," "anticipates," "intends," "plans," "could," "believes," "estimates" and similar expressions. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results to be materially different from any future results expressed or implied by the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to continue as a going concern, our ability to obtain additional capital to meet our liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials of our product candidates; our ability to successfully complete research and further development and commercialization of our product candidates; the uncertainties inherent in clinical testing; the timing, cost and uncertainty of obtaining regulatory approvals; our ability to protect the Company’s intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company’s products; and the other factors listed under "Risk Factors" in our filings with the SEC, including Forms 10-K, 10-Q and 8-K. Investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this release. Except as may be required by law, the Company does not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. Matinas BioPharma’s product candidates are all in a development stage and are not available for sale or use. Investor Contact: LHA Investor Relations Jody Cain Jcain@lhai.com 310-691-7100

Phase 2Phase 3Clinical ResultQualified Infectious Disease Product

22 Aug 2023

·www.sciencedaily.com

New antifungal therapy for fungal meningitis

A team of researchers successfully tested a new antifungal therapy to treat fungal meningitis. A team of University of Minnesota Medical School researchers successfully tested a new antifungal therapy to treat fungal meningitis. The trial results were published today in the peer-reviewed journal Clinical Infectious Diseases. The research team tested a new oral formulation of the antifungal medication amphotericin among people who had HIV and cryptococcal meningitis -- a common fungal infection around the brain. Cryptococcal meningitis is the most common cause of central nervous system infection in people living with HIV worldwide. Conventional amphotericin B can only be administered directly into veins and is highly toxic. The new lipid nanocrystal formulation -- which was tested in the EnACT trial -- can be taken orally and is non-toxic. "An orally administered amphotericin that is effective against nearly all fungus and non-toxic sounds like the holy grail of antifungal medicines. While further clinical trials are needed in other fungal conditions, the EnACT trial establishes proof of concept for the safe and effective treatment of invasive fungal infections," said David Boulware, MD, MPH, an infectious disease physician and professor at the University of Minnesota Medical School and M Health Fairview. Dr. Boulware is also the senior investigator of the EnACT trial. In this randomized trial, 141 HIV-positive people with cryptococcal meningitis received the oral amphotericin combined with oral flucytosine. This combination was found to be promising for cryptococcal meningitis in regard to antifungal activity, similar survival and less toxicity in comparison to intravenous amphotericin B. Statistically fewer lab abnormalities occurred with the six weeks of LNC-enabled oral amphotericin B compared to one week of intravenous amphotericin B. In the group given two IV loading doses then the experimental oral amphotericin formulation, 90% of participants survived >4 months compared to 85% who received one week of standard intravenous amphotericin. "With the rising incidence of life-threatening fungal infections, our currently available conventional methods are limited by rising rates of drug resistance and toxicities," said Mahsa Abassi, DO, assistant professor at the U of M Medical School and co-investigator on the trial. "The development of new antifungal regimens that are orally available, less toxic, and can treat highly resistant fungal infections is crucial." The trial was conducted in partnership with researchers from the U of M's Medical School, School of Public Health, the Infectious Diseases Institute of Makerere University in Uganda and Matinas BioPharma, a clinical-stage biopharmaceutical company. "We are very pleased that the important EnACT data are being shared with the clinical and scientific community at large through publication in this peer-reviewed journal," said Theresa Matkovits, PhD, and Chief Development Officer of Matinas. "The results from EnACT in cryptococcal meningitis and our experience with patients enrolled in our ongoing Compassionate/Expanded Use Access Program support our belief that MAT2203 has the potential to become an important part of the regimen for treatment of invasive fungal infections, including in the highest-need patients who require longer-term treatment and have limited or no treatment options. The publication of the EnACT data in Clinical Infectious Diseases is yet another milestone for our development program. We would like to thank all the EnACT participants, our dedicated investigators, and the entire clinical study team in Uganda for their commitment to this important clinical trial." Funding for the EnACT trial was provided by the National Institutes of Health's National Institute of Neurological Disorders and Stroke.

Clinical ResultClinical StudyQualified Infectious Disease Product

100 Deals associated with Flucytosine

External Link

KEGG	Wiki	ATC	Drug Bank
D00323	Flucytosine	J02AX01 D01AE21	DB01099

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Fungemia	JP	Kyowa Pharmaceutical Industry Co., Ltd.	31 May 1988
Mycoses	CN	Jinghua Pharmaceutical Group Nantong Co. Ltd.	01 Jan 1982
Meningitis, Fungal	JP	Kyowa Pharmaceutical Industry Co., Ltd.	13 Mar 1979
Respiratory Tract Infections	JP	Kyowa Pharmaceutical Industry Co., Ltd.	13 Mar 1979
Candidiasis	US	Bausch Health US LLC	26 Nov 1971
Cryptococcosis	US	Bausch Health US LLC	26 Nov 1971

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Liver Metastases	Phase 2	FR	Transgene SA	17 Jan 2020
Colorectal Liver Metastases	Phase 2	GB	Transgene SA	17 Jan 2020
Metastatic Colorectal Carcinoma	Phase 2	FR	Transgene SA	17 Jan 2020
Metastatic Colorectal Carcinoma	Phase 2	GB	Transgene SA	17 Jan 2020
Colorectal Cancer	Phase 2	BE	Transgene SA	16 Oct 2018
Colorectal Cancer	Phase 2	ES	Transgene SA	16 Oct 2018
Recurrent Glioblastoma	Phase 2	FR	Transgene SA	12 Oct 2017
Meningitis, Cryptococcal	Phase 2	KE	Bausch Health Americas, Inc.	01 Sep 2013
Hepatocellular Carcinoma	Phase 1	FR	Transgene SA	01 Sep 2009

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2023 Manual	Phase 1	Recurrent Prostate Carcinoma	15	Ad5-yCD/mutTKSR39rep-hIL-12+5-fluorocytosine+Valganciclovir	dfgnnydrxs(yknorwyvik) = qqyiyoluhi arniopziru (xbunfeealp ) View more	Positive	14 Apr 2023
NCT02015819 (CTgov)	Phase 1	Gliosarcoma \| Glioblastoma \| WHO Grade III Mixed Glioma ... View more	16	NSC+5-FC (Dose Level 1: (NSC 5x10^7 and 5-FC 37.5 mg/kg))	kcrbxtifjv(xhzvhoyzbw) = tevuqhklmo csmnwlltxh (fiwnaivmqq, vcmrvurhws - mbxlyhjxit)	-	29 Sep 2021
				NSC+5-FC (Dose Level 2: (NSC 1x10^8 and 5-FC 37.5 mg/kg))	kcrbxtifjv(xhzvhoyzbw) = ojqszfxvpp csmnwlltxh (fiwnaivmqq, frxzgddbmr - qyweltylyu)
NCT02576665 (Toca 6, SITC2019)	Phase 1	Solid tumor	21	Toca 511	vjjhxkvdsy(ylwtnzstbx) = no related Grade 4 adverse events tdezboyfza (cidemqjxem )	Positive	01 Nov 2019
ASGCT2019	Not Applicable	Esophageal Carcinoma	-	Toca 511	bdlgohrrsu(uhcqcvjwsb) = tumor growth in Toca 511/5-FC treated group was significantly inhibited compared to control group rnxkapcape (nyafqdskgx ) View more	-	22 Apr 2019
				Toca FC
NCT01470794 (S23.006, AAN2018)	Phase 1	Recurrent Malignant Glioma IDH1 wildtype \| IDH1 mutant	23	Toca 511	pkpdsjlwxb(kmegxdwsbx) = kojxbfdwgr aipkvoqxlp (iyasczpulr ) View more	Positive	10 Apr 2018
NCT00978107 (Pubmed \| Ann Oncol) Manual	Phase 1	Liver Cancer	16	TG4023+flucytosine	kybyuzzrmq(lbmfxdnslh) = 4 × 108 p.f.u. xgekypheag (bjibpdtwsk ) View more	Positive	01 Jan 2017
NCT02414165 (Pubmed \| Sci Transl Med) Manual	Phase 1	Recurrent Malignant Glioma	45	5-fluorocytosine+vocimagene amiretrorepvec	mygnqkghmh(cflkdfuqjp) = atpfacapat gilzucyosv (ivdazmwxkf, 10.8 - 20.0)	Positive	01 Jun 2016
				5-fluorocytosine+subgroup from an external control	-
AAI2016	Not Applicable	Neoplasms	-	Toca 511+5-FC	qjdlwgshtg(xqewjtcwau) = ufheviwrci tupqyprrxy (rpklprphay ) View more	-	01 May 2016
				PBS	qjdlwgshtg(xqewjtcwau) = jqyzgnkvtu tupqyprrxy (rpklprphay ) View more
NCT01562132 (SToP-Crypto, CTgov)	Phase 2	Meningitis, Cryptococcal	6	fluconazole+Flucytosine (5FC Plus Fluconazole)	frjxswyuls(pxxipigggu) = fdxgxhynwr znrvvkbmcg (qisgbtfgnq, njhxjfvcpy - ehlemsjdao) View more	-	31 Aug 2015
				fluconazole (Fluconazole Alone)	frjxswyuls(pxxipigggu) = gknvwxsiax znrvvkbmcg (qisgbtfgnq, xopwpfanwq - hkjwpdoaub) View more
IAS2009	Not Applicable	-	44	Fluconazole 1200 mg/day	upyoygibxh(viunfqlriu) = ipvhgdqwat wnhhvyzjzz (ktebpziuec )	-	01 Jan 2009
				Fluconazole 1200 mg/day + Flucytosine 100 mg/kg/day	upyoygibxh(viunfqlriu) = dheqwwvval wnhhvyzjzz (ktebpziuec )

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