Amplyx Announces Positive Top-line Data in Antifungal Fosmanogepix Trial

Amplyx Pharmaceuticals announced positive topline data following the completion of its Phase 2 clinical trial of fosmanogepix as a first-line treatment for patients with invasive fungal infections caused by Candida. The trial met its primary efficacy endpoint, demonstrating a treatment success rate of 80%. Fosmanogepix was well tolerated with no treatment-related serious adverse events or discontinuations. In addition, fosmanogepix demonstrated potent in vitro activity against all Candida isolates obtained from patients in this study, including isolates resistant to other antifungal agents. More detailed results from the trial will be presented at an upcoming medical meeting.

"We are very encouraged that fosmanogepix demonstrated a high rate of treatment success, including activity against resistant pathogens, and was well tolerated in patients with invasive Candida infections. Importantly, patients were able to easily transition from intravenous to oral formulations during their treatment," said Michael R. Hodges, M.D., chief medical officer of Amplyx. "The positive efficacy and safety data from this trial continue to highlight the promise of fosmanogepix as a novel and differentiated treatment option for patients who develop life-threatening invasive fungal infections. We look forward to advancing the fosmanogepix program in invasive candidiasis towards registration, while continuing our proof-of-concept clinical trials in other invasive fungal infections, including invasive aspergillosis."

Amplyx is developing fosmanogepix, a broad-spectrum, oral and intravenous antifungal, representing a novel therapeutic class with the potential to treat pathogens resistant to current available antifungal agents. Additional Phase 2 studies of fosmanogepix are ongoing in patients with serious and life-threatening Aspergillus and rare mold infections, as well as infections caused by drug-resistant Candida auris. In 2019, the U.S. Centers for Disease Control recognized drug-resistant C. auris as an urgent threat to global public health, other drug-resistant Candida strains as serious threats, and the emergence of drug-resistant Aspergillus added to the watch list for global health threats, underscoring the need for innovation in the development of antifungals, especially those with a novel mechanism of action.

"There is a dire need for safe and effective new antifungal agents as there have been no new drugs approved in the past two decades, coupled with the growing number of immunocompromised patients who are at increased risk for developing these life-threating infections," said Peter Pappas, M.D., professor of medicine, division of infectious diseases, University of Alabama at Birmingham. "Fosmanogepix has the potential to be the first in a new class of antifungal agents and an important addition to the treatment armamentarium for patients with difficult-to-treat and deadly invasive fungal infections. The current pandemic has highlighted how devastating infectious diseases can be and reinforces the need for new and novel anti-infective agents capable of combating emerging threats."

This was a multicenter, open-label, non-comparative, single-arm study evaluating the efficacy and safety of fosmanogepix for the first-line treatment for candidemia including suspected or confirmed antifungal-resistant candidemia in non-neutropenic patients 18 years of age and older. Patients were treated with fosmanogepix for up to 14 days: 1000 mg intravenously twice a day for one day, then 600 mg intravenously once daily for at least two days, followed by either 600 mg intravenously once daily or 700 mg orally once daily. Short-term fluconazole (or susceptibility-appropriate alternative) could follow if completion of the treatment course was required beyond 14 days. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by the 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 susceptibility. A key secondary efficacy endpoint was survival at Day 30.

Invasive fungal infections (IFIs) represent a serious threat to millions of patients worldwide, resulting in more than 1.5 million deaths annually and mortality rates ranging from 15% to 65%.  These infections continue to be a global health issue, especially for critically ill patients in hospitals and patients with compromised immune systems, including cancer and transplant patients.

Fosmanogepix, is a novel, broad-spectrum antifungal agent being evaluated in multiple clinical trials in patients with life-threatening fungal infections.  Fosmanogepix demonstrated a high level of treatment success (80%) in a Phase 2, proof-of-concept study as first-line treatment of infections caused by Candida.  Additional Phase 2 studies of fosmanogepix are ongoing in patients with Aspergillus and rare mold infections, as well as infections caused by multi-drug-resistant Candida auris, a life-threatening fungal infection recently characterized as an "urgent" threat by the Centers of Disease Control (CDC).

Fosmanogepix has a novel mechanism of action, and its active moiety has shown broad-spectrum activity against common species of Candida and Aspergillus, including multi-drug resistant strains, such as C. auris and C. glabrata, as well as rare, hard-to-treat molds including Fusarium, Scedosporium and some fungi from the Mucorales order. Invasive fungal infections result in high mortality rates (30-80%), despite standard-of-care treatment. The frequency of fungi resistant to both the azole and echinocandin classes of drugs is increasing and there is a significant unmet medical need for a new, broad-spectrum antifungal agent.

Fosmanogepix has received Fast Track and Orphan Drug designations from the US FDA for seven separate indications and is also designated as a Qualified Infectious Disease Product (QIDP) for the treatment of four indications.