oral amphotericin B (MAT2203) / Matinas - LARVOL DELTA

New approaches for cryptococcosis treatment and prevention-a systematic review. (PubMed, J Thorac Dis) - "MAT2203 demonstrated non-inferior efficacy with improved safety compared with intravenous amphotericin B. Several novel antifungal agents have entered clinical development, whereas repurposed drugs have shown limited clinical benefit...Although most remain at the preclinical or early clinical stage, advances in host-directed immunotherapy, nanomedicine, and novel antifungal development provide promising opportunities to improve treatment efficacy, safety, and accessibility. Well-designed clinical studies are needed to facilitate clinical translation."

Journal • Review • Infectious Disease • IFNG

Successful salvage treatment of Mucor nidicola and Aspergillus calidoustus co-infection with oral encochleated amphotericin B (MAT2203) in a pediatric patient with acute myeloid leukemia. (PubMed, Med Mycol Case Rep) - "Antifungal treatment of invasive fungal infections (IFI) in immunocompromised children is challenging. We present a case of rhinocerebral and pulmonary IFI caused by Mucor nidicola and Aspergillus calidoustus with limited azole susceptibility successfully treated with MAT2203 after developing toxicity from intravenous liposomal amphotericin B."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pediatrics

Pulmonary Aspergillosis Treated With Oral Amphotericin B (MAT2203) in a Patient With HIV-Related Cryptococcal Meningitis. (PubMed, Clin Case Rep) - "The case highlights the need to consider aspergillosis in patients with cryptococcal infections and unexplained respiratory symptoms, as well as in smear-negative pulmonary tuberculosis. When standard triazoles are unavailable, novel oral amphotericin B (MAT2203) successfully treated both invasive pulmonary aspergillosis and cryptococcosis in this case of coinfection, warranting further evaluation."

Journal • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Successful Cultivation of Oral Mucosal Epithelial Sheet Following Antifungal Therapy in Cases With Limbal Stem Cell Deficiency. (PubMed, Cornea) - "This case series emphasizes the importance of preoperative dental assessment and oral antifungal treatment in preventing microbial contamination during epithelial sheet preparation for COMET."

Journal • Immunology • Steven-Johnson Syndrome • Transplantation

New antifungals for the treatment of invasive mold disease. (PubMed, Clin Microbiol Infect) - "Development of new antifungal agents is challenging due to limited target sites, emergence of resistance, and adverse toxicity profiles. However, clinical data from fosmanogepix, olorofim, and encochleated amphotericin B are promising in both clinical efficacy and safety for the treatment of invasive mold infections. These new agents offer alternative options for difficult to treat infections, while providing promising efficacy and improved safety outcomes."

Journal • Review • Infectious Disease

Successful Control of Refractory Coccidioides Meningitis With MAT2203. (PubMed, Open Forum Infect Dis) - "In 2017 a previously healthy construction worker developed coccidioidal pneumonia and meningitis and was treated with liposomal amphotericin B and oral fluconazole...He required multiple changes in azoles and eventually an Ommaya reservoir so that he could receive periodic IT amphotericin B plus corticosteroids while continuing oral isavuconazole...A trial of the investigational antifungal olorofim also failed...After 6 months of MAT2203 (without any IT or intravenous amphotericin B), Coccidioides antigen in the ventricular CSF was undetectable for the first time and remained so with normalization of glucose and cell counts. MAT2203 may offer an oral therapeutic option for refractory cases of Coccidioides meningitis."

Journal • CNS Disorders • Infectious Disease • Pneumonia • Respiratory Diseases • Vasculitis

Evaluating Desirability of Outcome Ranking (DOOR) and Win Ratio for Hierarchical Composite Endpoints in Cryptococcal Meningitis Trials. (PubMed, Clin Infect Dis) - "Hierarchical composite endpoints were feasible to implement in cryptococcal meningitis clinical trials and can enhance clinical relevance, especially in non-inferiority designs where safety and tolerability matter. The two statistical approaches provided complementary perspectives - DOOR offering absolute ranks and Win Ratio providing a more interpretable relative treatment effect estimate."

Clinical • Journal • CNS Disorders • Infectious Disease

New and emerging drugs for the treatment of invasive fungal infections. (PubMed, Expert Opin Pharmacother) - "Data were identified using PubMed searches for the terms 'antifungal,' 'olorofim,' 'SUBA-itraconazole,' 'ibrexafungerp,' 'rezafungin,' 'fosmanogepix,' and 'encochleated amphotericin B.' Approved agents include ibrexafungerp, an oral triterpenoid inhibitor of 1,3-β-D-glucan synthase; rezafungin, a long-acting echinocandin with weekly dosing; and SUBA-itraconazole, a reformulation of itraconazole with more consistent absorption. Despite improvements, gaps remain in treatments for severe IFI, particularly given increasing resistance. These agents represent significant advances, but further research is needed to define their use in patient management."

Journal • Review • Dermatology • Infectious Disease

Optimization and prioritization of paediatric drugs for visceral leishmaniasis. (PubMed, Front Pediatr) - "The group prioritized a 20 mg scored, dispersible tablet formulation of miltefosine and an oral solid dosage form of amphotericin B, acknowledging recent developments in allometric dosing for miltefosine and ongoing research for the development of oral amphotericin B. For miltefosine, this prompted an ongoing update of the WHO Prequalification Expression of interest to promote generic manufacturing. A compound with a new mechanism of action, LXE408, which is currently being investigated in Phase II, was included in the PADO watch list, signalling that paediatric investigations should start as soon as enough data are available from adult studies, not to delay access to latest available innovations for children with VL."

Journal • Infectious Disease • Pediatrics

Experience of research nurses with oral encochleated amphotericin B for treatment of cryptococcal meningitis in a resource-limited setting. (PubMed, BMC Infect Dis) - P1/2 | "Oral amphotericin B was generally safe and well tolerated. However, it requires some training for the nurse, patient and care takers for better administration, adherence and treatment outcomes."

Journal • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease

Antifungal pipeline: New tools for the treatment of mycoses. (PubMed, Rev Iberoam Micol) - "New antifungal agents, such as ibrexafungerp, rezafungin, oteseconazole, and miltefosine, offer novel mechanisms of action along with reduced toxicity...This review provides a comprehensive overview of these new agents and their mechanisms, and explores the challenges and roles of antifungal drugs in LMICs, where the burden of fungal infections is high. Continued research and development are essential to address the rising incidence and resistance of fungal infections globally."

Journal • Dermatology • Infectious Disease

Howell-Jolly Body-Like Neutrophil Inclusions Following Hematopoietic Stem Cell Transplantation: A Case Report. (PubMed, Am J Case Rep) - "The therapeutic regimen was escalated to include oral amphotericin B, while continuing tacrolimus and discontinuing all other immunosuppressants. CONCLUSIONS The present case highlights the presence of Howell-Jolly body-like inclusions within the cytoplasm of neutrophils observed in the peripheral blood smear of a patient after hematopoietic stem cell transplantation. Morphological analysis suggests that the emergence of these inclusions is highly likely to be induced by medications used in the treatment of GVHD."

Journal • Bone Marrow Transplantation • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Human Immunodeficiency Virus • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Transplantation

Use of Miconazole Cream As Adjunctive Therapy to Treat Isolated Sinus Mucormycosis: A Case Report and Literature Review. (PubMed, Cureus) - "An extensive surgical debridement and liposomal amphotericin B were the mainstay of treatment. Therefore, recent studies have proposed new adjuvant modalities, such as hyperbaric oxygen therapy and local treatment with amphotericin B. In this study, we propose a new adjuvant therapy using local miconazole cream which showed a good prognosis with the combination of oral amphotericin B and surgical debridement. This highlights the necessity for extensive future clinical trials to validate its effectiveness in treating isolated sinus mucormycosis."

Journal • Review • Infectious Disease • Metabolic Disorders • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Cryptococcal invasion: a comprehensive case of adrenal and systemic infection amid immunosuppression. (PubMed, BMC Infect Dis) - "The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination."

Journal • CNS Disorders • Endocrine Cancer • Infectious Disease • Inflammation • Myelofibrosis • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Development and deployment of a solid oral amphotericin B dosage form to treat visceral leishmaniasis within a pediatric population. (PubMed, PLoS Negl Trop Dis) - "Currently, the intravenous single-dose liposomal amphotericin B is the first choice for the treatment of VL. To solve this problem, the development of a solid oral amphotericin B formulation that is cost-effective, safe, tropically stable, and easy to swallow, making it more accessible to children, particularly in rural communities having limited access to medical clinics or trained healthcare professionals is imperative. This viewpoint will discuss the opportunities and challenges of developing an oral amphotericin B formulation for a pediatric population."

Journal • Review • Infectious Disease • Pediatrics

Successful Treatment of Refractory Cutaneous Protothecosis With MAT2203, an Oral Lipid Nanocrystal Formulation of Amphotericin B. (PubMed, Open Forum Infect Dis) - "Prototheca wickerhamii is a rare cause of cutaneous and systemic infection that requires long treatment courses with potentially toxic medications. We describe a patient with cutaneous protothecosis refractory to triazole monotherapy who experienced clinical and radiographic improvement with the novel oral lipid nanocrystal formulation of amphotericin B without experiencing toxicity."

Journal • Infectious Disease

Oral Lipid Nanocrystal Amphotericin B (MAT2203) for the Treatment of Invasive Fungal Infections. (PubMed, Open Forum Infect Dis) - "MAT2203 was well tolerated with only modest gastrointestinal adverse effects. This new oral formulation might provide a safer treatment option for patients requiring extended courses of AmB."

Journal • Gastrointestinal Disorder • Infectious Disease

CAMB/MAT2203 in Patients With Mucocutaneous Candidiasis (clinicaltrials.gov) - P2 | N=4 | Completed | Sponsor: Matinas BioPharma Nanotechnologies, Inc. | Phase classification: P2a ➔ P2

Phase classification • Candidiasis

Efficacy of an oral lipid nanocrystal formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis. (PubMed, Antimicrob Agents Chemother) - "We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to Rhizopus arrhizus var. Furthermore, while both MAT2203 and LAMB treatment resulted in a significant reduction of ~1.0-2.0log and ~2.0-2.5log in Rhizopus delemar or M. circinelloides lung and brain burden vs placebo mice, respectively, LAMB significantly reduced tissue fungal burden in mice infected with R. delemar vs tissues of mice treated with MAT2203. These results support continued investigation and development of MAT2203 as a novel and oral formulation of amphotericin for the treatment of mucormycosis."

Journal • Preclinical • Infectious Disease

Successful In Vivo Oral Delivery of Biologically Active and Therapeutic Anti-Inflammatory mRNA-Targeted Oligonucleotides with a Lipid Nanocrystal Delivery Platform (ASGCT 2024) - "Matinas BioPharmas' lipid nanocrystal (LNC) platform successfully delivers oral amphotericin-B in patients with cryptococcal meningitis, and other ex vivo work has shown avid LNC uptake by innate immune cells... In the imiquimod psoriasis model (Figure 1) daily oral administration of an LNC formulation of the IL-17A targeted oligo resulted in both knock-down of skin IL-17 mRNA, and significant improvement in clinical parameters of redness and scaling... The LNC delivery platform can successfully orally deliver biologically active (and potentially therapeutic) oligonucleotides targeting key cytokines in inflammatory disease models. While these initial results are promising, there is still some individual heterogeneity of response; future work will be focused on optimizing the LNC formulations to improve delivery efficiency, increase their potency, and extend the application of oral cytokine-targeting oligo therapeutics in other inflammatory diseases. models.Plain..."

Preclinical • CNS Disorders • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Psoriasis • IL17A • TNFA

Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective. (PubMed, J Pediatric Infect Dis Soc) - "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."

Journal • Infectious Disease • Pediatrics • Transplantation

New treatment options for critically important WHO fungal priority pathogens. (PubMed, Clin Microbiol Infect) - "While the limited number of targets and the emergence of resistance have posed challenges to antifungal treatment, new drugs such as ibrexafungerp, rezafungin, fosmanogepix, or olorofim have shown promising clinical efficacy. These drugs not only provide alternative options for invasive fungal infections but also alleviate treatment in outpatient settings. More clinical data, implementation of stewardship programs, and surveillance, including utilization of drugs in agriculture are necessary to prevent resistance development and ensure the safety and efficacy of these new agents."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Update on therapeutic approaches for invasive fungal infections in adults. (PubMed, Ther Adv Infect Dis) - "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."

Journal • Review • Bone Marrow Transplantation • Immunology • Infectious Disease • Oncology • Transplantation

5-Flucytosine Longitudinal Antifungal Susceptibility Testing of Cryptococcus neoformans: A Substudy of the EnACT Trial Testing Oral Amphotericin. (PubMed, Open Forum Infect Dis) - "There is no evidence of baseline resistance to 5FC or incident resistance during combination therapy with oral or IV amphotericin B in Uganda. Oral amphotericin B can safely be used in combination with 5FC."

Clinical • Journal • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease

MAT2203, A Novel Oral Delivery of Amphotericin B (AMB), in Phase 3 Development for the Treatment of Invasive Fungal Infections (Matinas BioPharma) (IDWeek 2023) - No abstract available

P3 data • Infectious Disease