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Highlights from

The European Congress of Clinical Microbiology & Infectious Diseases

29th Annual Meeting

Amsterdam 13-16 April 2019

Novel oral antifungal shows favourable response in patients with refractory fungal disease

Take-home messages
  • Phase III preliminary data show that oral ibrexafungerp provided a favourable response in the majority of patients with difficult-to-treat Candida spp
  • Common treatment-related AEs included mild-to-moderate diarrhoea and nausea
  • Treatment was generally well tolerated
“It’s active against azole- and most echinocandin-resistant strains, which is good news”

Professor Oliver Cornely, Director and Chair, Translational Research & Clinical Trials Center, University of Cologne, Germany

Phase III interim data on the use of oral ibrexafungerp in difficult-to-treat Candida spp, including those caused by non-albicans Candida, were released at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 13-16 April, Amsterdam by Professor Oliver Cornely, Director and Chair of the Translational Research & Clinical Trials Center, University of Cologne, Germany.

Ibrexafungerp (formerly SCY-078) is a novel glucan synthase inhibitor that can be administered orally or intravenously. “It’s active against azole- and most echinocandin-resistant strains, which is good news,” explained Professor Cornely, adding that it has broad-spectrum antifungal activity against Candida, Aspergillus and Pneumocystis.

The trial in question, ‘FURI’, focused on Candida only. The primary aim of this open-label, single-arm, phase III trial was to evaluate the safety and efficacy of oral ibrexafungerp, as determined by a data monitoring committee that assessed global success (a composite of clinical, microbiological, serological and/or radiological responses) at the end of treatment.

The trial included adult patients from 14 centres from four different countries, with acute or chronic invasive candidiasis (including candidaemia) and/or acute or chronic severe mucocutaneous candidiasis. Patients were either intolerant or refractory to ≥1 antifungal standard of care, or had proven intolerance or unacceptable toxicity to it, and were also included if long-term IV antifungal therapy was not feasible or desirable, or if other oral antifungal alternatives were not appropriate.

Patients were excluded if they had any central nervous system, heart or eye involvement, or an inappropriately controlled fungal infection source (eg persistent catheters, devices or abscess). They were given oral ibrexafungerp 750 mg twice daily for 2 days, followed by 750 mg once daily until end of treatment, which was a maximum of 90 days, at investigator discretion. Follow-up was 6 weeks after the treatment had ended.

Of the 20 patients that completed treatment, 11 (55%) had a complete/ partial response (CR/PR), 6 (30%) had stable disease (SD) and 2 (10%) had progressive disease (PD). One case was considered indeterminate. Mean treatment duration was 36.4 days (range: 7-90).

90-day global response to oral ibrexafungerp by invasive fungal disease:

Mucocutaneous candidiasisNCR/PRSDPDIndetermin.
Oesophageal candidiasis64200
Oropharyngeal candidiasis21010
Chronic mucocutaneous candidiasis1*0100
Intra-abdominal infections52111
Invasive candidiasisNCR/PRSDPDIndetermin.
Candidaemia and endocardial infection11000
Surgical wounds infection11000

Two patients (one with chronic mucocutaneous candidiasis and one with spondylodiscitis) continued therapy past 90 days at the request of the investigator.

“If we take a new angle and sort them by the pathogen, C. glabrata [n=11] was the frequent one, C. krusei [n=4] and C. albicans [n=3] followed,” he continued, stating that there was no specific pattern between pathogens in terms of global response.

Professor Cornely proceeded to cover the interim safety results “The most common drug-related AEs were mild-to-moderate diarrhoea, nausea and, less frequently so, vomiting. The compound was generally well tolerated, [and] there were no deaths reported due to progression of fungal infections specifically.” There was one death in the study due to bacterial liver abscess.

Overall, the interim efficacy and safety results are encouraging. Infections caused by non-albicans Candida are on the rise, posing a significant global health threat, and ibrexafungerp could add to the armamentarium against these species as well as other invasive fungal pathogens.

Based on Cornely O A, Ostrosky-Zeichner L et al. Favorable response to oral ibrexafungerp (formerly SCY-078) in patients with refractory fungal diseases, interim analysis by pathogen from a phase 3 open-label study (FURI) (oral session L0010). Presented on Tuesday 16 April 2018.

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