Session : Innovations and Updates in Mycology

149 - Efficacy of Cochleated Amphotericin B (CAMB) in Mouse and Human Mucocutaneous Candidiasis

Oral Abstract

Location: On Demand

Background: Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC), often requiring long-term azole-based treatment. Due to increasing azole resistance, alternative treatments are desirable. Acquired resistance to amphotericin B (AMB) is rare but AMB use is limited by parenteral administration and nephrotoxicity. Cochleated AMB (CAMB) is a new oral formulation of AMB and thus an attractive option for oropharyngeal candidiasis (OPC), esophageal candidiasis (EC) and vulvovaginal candidiasis (VVC). We assessed the efficacy of CAMB in mouse models of OPC and VVC and in 4 patients with azole resistant CMC manifesting as OPC, EC or VVC.

Methods: Act1^-/-mice were infected with C. albicans in models of OPC and VVC and were treated once daily via oral gavage with CAMB or vehicle or intraperitoneal AMB-deoxycholate (AMBd) from day 1 through 4 post-infection (pi). At day 5 pi, the tongue or vaginal tissue was harvested to quantify fungal burden. Patients with azole resistant CMC enrolled in a phase 2A CAMB dose escalation study. The primary endpoint was clinical improvement at 2 weeks based on an efficacy scale, followed by optional extension for long-term suppression of CMC to assess safety and efficacy.

Results: CAMB-treated mice had significantly reduced tongue and vaginal tissue fungal burden compared to vehicle-treated mice, while they exhibited comparable fungal control relative to AMBd-treated mice. Among 4 CAMB-treated patients, 3 reached clinical efficacy by 2 weeks at a dose of 400 mg twice daily and one reached clinical efficacy at 200 mg twice daily. Three of 4 patients continued on the extension phase past 48 months with sustained clinical improvement of OPC and EC; patient #3 had relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical response was not seen for onychomycosis or VVC. CAMB was safe and well-tolerated without renal toxicity.

Conclusion: Oral administration of CAMB in IL-17-signaling deficient mice resulted in reduced tongue and vaginal tissue fungal burden during mucosal C. albicans infections. A proof-of-concept clinical trial in humans with inherited CMC showed efficacy in OPC and EC with good tolerability and safety.

Presenting Author(s)

Jigar V. Desai, PhD

Research Fellow
Fungal Pathogenesis Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health
Bethesda, MD

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Slides Slides and Audio

Co-Author(s)

AU

Amanda Urban, DNP, CRNP

Nurse Practitioner
Leidos Biomedical Research
Bethesda, Maryland

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DS

Doris Z. Swaim, RN, BSN, CCRC

Nurse protocol coordinator
Leidos Biomedical Research
Bethesda, Maryland

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
EF

Elise Ferre, PA-C, MPH

Physician Assistant
NIAID
Bethesda, Maryland

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BC

Benjamin Colton, PharmD

Clinical Pharmacy Specialist
National Institutes of Health
Bethesda, Maryland

Disclosure: Merck (Shareholder)Pfizer (Shareholder)
RL

Ruying Lu, n/a

Senior Director
Matinas BioPharma Inc.
Bridgewater, New Jersey

Disclosure: Matinas BioPharma Inc. (Employee)Matinas BioPharma Inc. (Employee, Shareholder)
TM

Theresa Matkovits, Ph.D.

Chief Development Officer
Matinas BioPharma
Bedminster, New Jersey

Disclosure: Matinas BioPharma (Employee, Shareholder)
Raphael J. Mannino, PhD

Chief Scientific Officer
Matinas BioPharma, Inc.
Bridgewater, New Jersey

Disclosure: Matinas BioPharma Inc. (Employee, Shareholder)
ET

Edmund Tramont, MD

Assoc. Dir Special Projects DCR/NIAID/NIH
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Michail Lionakis, MD, ScD

Chief, Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland

Disclosure: Matinas BioPharma (Research Grant or Support)
AF

Alexandra Freeman, MD

Senior clinician
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.