“The compound appears to be safe and well-tolerated, [and we observed] excellent efficacy based on a very small sample size,” Peter G. Pappas, MD, said.
Fungal infections represent a massive health burden in terms of both mortality and cost, as they contribute to an estimated 1.5 million deaths per year globally and were estimated in 2017 to have driven $7.2 billion in direct medical costs, according to the US Centers for Disease Control and Prevention (CDC).
Consider, too, that there are only a handful of classes of antifungals and it is clear why the need for novel agents with unique mechanisms of action is so urgent.
In results from a phase 2 proof-of-concept study presented virtually at ID Week 2020, investigators with the University of Alabama at Birmingham and Amplyx Pharmaceuticals report favorable safety and efficacy data for fosmanogepix (FMGX) as first-line treatment for patients with candidemia.
FMGX targets more resistant Candida spp, specifically the fungal enzyme Gwt1, and is formulated for both oral and intravenous (IV) administration. The global, multicenter, open-label, non-comparative study enrolled eligible participants who had a recent diagnosis of candidemia as evidenced by a positive blood culture for Candida spp within 96 hours prior to study entry and with ≤2 days of prior antifungal treatment. Exclusion criteria included neutropenia, C krusei infection, and deep-seated Candida infections.
The modified intent-to-treat (mITT) population included patients with candidemia that had been diagnosed within 96 hours of starting the study drug and who received at least 1 dose of FMGX. Outcome at end of study treatment (EOST) as determined by an independent data review committee (DRC) was the primary efficacy outcome. Success was defined as clearance of Candida from blood cultures with no additional treatment with antifungals and survival at EOST.
The course of treatment was up to 14 days of FMGX, administered at 1000 mg IV twice a day for 1 day, then 600 mg IV 4 times a day for at least 2 days, followed by either 600 mg IV 4 times a day or 700 mg by mouth 4 times a day. If treatment was required beyond 14 days, patients could receive fluconazole (or appropriate alternative).
Those included in the mITT, 20 of 21 subjects, received a median 11 days of FMGX (range 5-14). IV FMGX was administered to all subjects, while 48% (10/21) received FMGX orally. At EOST, the success rate as determined by the DRC was 80% (16/20).
Day-30 survival rate was 85% (17/20), and the 3 deaths were not related to the study drug. There were no serious treatment-related adverse events or discontinuations reported.
Investigators tested all Candida isolates for antifungal susceptibility and found FMGX to have potent in vitro activity against all study Candida spp (EUCAST MIC range 0.001–0.03 µg/ml), including those resistant to other antifungal treatments.
Peter G. Pappas, MD, professor of medicine at the University of Alabama at Birmingham, and presenting author of the study, told Contagion®that development of a phase 3 trial is now in progress.
“The compound appears to be safe and well-tolerated, [and we observed] excellent efficacy based on a very small sample size,” Pappas said.
The study, “Clinical Safety and Efficacy of Novel Antifungal, Fosmanogepix, in the Treatment of Candidemia: Results from a Phase 2 Proof of Concept Trial,” was presented virtually at ID Week 2020.