Session : Innovations and Updates in Mycology

147 - Clinical Safety and Efficacy of Novel Antifungal, Fosmanogepix, in the Treatment of Candidemia: Results from a Phase 2 Proof of Concept Trial

Oral Abstract

Location: On Demand

Background: Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, that has broad-spectrum activity against both yeasts, molds, and dimorphic fungi, including fungi resistant to other antifungal agents. FMGX has a favorable safety profile, reduced potential for clinically significant drug-drug interactions, and is formulated for IV and oral administration.

Methods: This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp. within 96 hrs prior to study entry, with ≤2 days of prior antifungal treatment were eligible. Patients with neutropenia, C. krusei infection, or deep-seated Candida infections were excluded. Patients were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Short-term fluconazole (or appropriate alternative) could follow if treatment was required beyond 14 days. Patients with a diagnosis of candidemia within 96 hrs of start of study drug who received at least 1 dose of FMGX were included in the mITT population. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee (DRC). Successful outcome was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at EOST. All Candida isolates were tested for antifungal susceptibility.

Results: A total of 21 subjects were enrolled in the study: 20 were included in the mITT. Median duration of FMGX was 11 days (range 5-14). All subjects received IV FMGX, 48% (10/21) received PO FMGX. The DRC-assessed success rate at EOST was 80% (16/20). Survival at day 30 was 85% (17/20); 3 deaths were not related FMGX. FMGX was well-tolerated with no treatment-related serious adverse events or discontinuations. FMGX had potent in vitro activity against all study Candida spp. (EUCAST MIC range 0.001–0.03 µg/ml) including those resistant to other antifungal agents.

Conclusion: FMGX was safe, well-tolerated, and demonstrated proof of concept with a high level of treatment success in patients with candidemia.

Presenting Author(s)

Peter G. Pappas, MD

Professor of Medicine
University of Alabama at Birmingham
Birmingham, Alabama

Disclosure: Amplyx : Advisor or Review Panel member (Status: Ongoing); Astellas : Grant/Research Support (Status: Ongoing), Scientific Research Study Investigator (Status: Ongoing); Cidara : Advisor or Review Panel member (Status: Ongoing), Scientific Research Study Investigator (Status: Ongoing); F2G : Advisor or Review Panel member (Status: Ongoing); Mayne Pharma : Scientific Research Study Investigator; Merck : Grant/Research Support (Status: Ongoing); Scynexis : Consultant (Status: Ongoing), Grant/Research Support (Status: Ongoing)

Slides Slides and Audio

Co-Author(s)

BK

Bart Jan Kullberg, M.D., FRCP, FIDSA

Professor of Medicine and Infectious Diseases
Radboud univerity medical center
Nijmegen, Gelderland, Netherlands

Disclosure: Amplyx (Advisor or Review Panel member)
Jose A. Vazquez, MD, FIDSA

Professor of Medicine
Medical College of Georgia at Augusta University
Augusta, Georgia

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

Ilana Oren, MD

head of transplant infectious diseases
RHCC
Kiryat Motzkin, Hefa, Israel

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

Galia Rahav, MD

Head of Infectious Disease Unit
Sheba Medical Center and Tel Aviv University
Ramat Gan, HaMerkaz, Israel

Disclosure: AstraZeneca (Scientific Research Study Investigator)
MA

Mickaël Aoun, MD

Head of the Infectious Diseases
Institut Jules Bordet
Brussels, Brussels Hoofdstedelijk Gewest, Belgium

Disclosure: Amplyx Pharmaceuticals (Scientific Research Study Investigator)
Pierre Bulpa, MD

Professor
Mont-Godinne University Hospital, CHU UCL Namur
Yvoir, Namur, Belgium

Disclosure: Amplyx Pharmaceuticals (Scientific Research Study Investigator)
RB

Ronen Ben-Ami, MD

Head of Infectious Diseases Unit
Tel Aviv Sourasky Medical Center
Tel Aviv, Tel Aviv, Israel

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

Ricard Ferrer, MD, PhD

Critical Care physician
Vall d’Hebron University Hospital
Barcelona, Catalonia, Spain

Disclosure: Shionogi B.V. (Advisor or Review Panel member)
TM

Todd P. McCarty, MD

Assistant Professor
University of Alabama at Birmingham; Birmingham VA Medical Center
Birmingham, Alabama

Disclosure: Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator)
George R. Thompson, MD

Associate Professor of Medicine
UC-Davis
Sacramento, California

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

Sara Barbat, BSN, RN

Senior Director Clinical Operations
Amplyx Pharmaceutical
San Diego, California

Disclosure: Amplyx Pharmaceuticals (Employee)
PW

Pamela Wedel, BSc

Vice President, Clinical Operations
Amplyx Pharmaceuticals
La Mesa, California

Disclosure: Amplyx Pharmaceuticals (Employee)
IO

Iwonka Oborska, PhD

Independent consultant
Amplyx
Horsham, England, United Kingdom

Disclosure: Amplyx Pharmaceuticals (Consultant, Independent Contractor)
HS

Haran T. Schlamm, MD

Consultant
Amplyx Inc
Rancho Santa Fe, California

Disclosure: Amplyx (Consultant)
MH

Michael Hodges, BSc. MD

Chief Medical Officer
Amplyx Pharmaceuticals
San Diego, California

Disclosure: Amplyx Pharmaceuticals Inc. (Employee)