Future Fungal Fighters in Dermatology: Novel Antifungal Drug Pipeline

May 2022 | Volume 21 | Issue 5 | 496 | Copyright © May 2022


Published online April 18, 2022

Yasmin Khalfe MD, Theodore Rosen MD

Department of Dermatology, Baylor College of Medicine, Houston, TX

Abstract
Over the last decade, major advances in antifungal drug development have occurred. Novel drugs in the pipeline include ME1111, MAT2203, rezafungin, ibrexafungerp, olorofim, fosmanogepix, MGCD290, VT-1161, NP213, T-2307, aureobasidin A, and nikkomycin Z. While most of these “future fungal fighters” have been developed to address invasive fungal infections (IFI), there is potential for dermatologists to benefit as these drugs may be adapted for superficial infections. Here, we review the major developments in novel antifungals and examine the ways in which dermatologists may gain from these recent innovations.

J Drugs Dermatol. 2022;21(5):496-501. doi:10.36849/JDD.6373

INTRODUCTION

As a specialty that commonly provides the diagnosis and/or treats cutaneous fungal infections, dermatologists commonly prescribe antifungal medications. The majority of fungal infections are superficial mycoses; however, invasive fungal infections (IFI) are a major cause of morbidity and mortality in humans worldwide, especially among the immunocompromised or immunosuppressed. In patients with IFI, the overall mortality rate is up to 45%, and the vast majority of fungal-related deaths result from Cryptococcus, Candida, Aspergillus, Histoplasma, and Coccidioides.1 As resistance associated with all types of fungal infections continues to rise globally, the need for new, effective, and safe antifungal treatment is crucial. Nonetheless, available drug options are limited. In India, for example, Singh et al showed that the effectiveness of four common oral antifungal drugs (fluconazole, griseofulvin, itraconazole, and terbinafine) had become limited in their effectiveness; at 8 weeks, the percent of patients cured was 42% for fluconazole, 14% for griseofulvin, 66% for itraconazole, and 28% for terbinafine.2 Additionally, there has been an emergence of novel resistant species globally, such as Candida auris.3

Fortunately, in recent years, there have been innovative developments in drugs that treat fungal infections (Table 1). These “future fungal fighters” are mostly being targeted as treatment for IFI’s. However, dermatologists may greatly benefit from the novel antifungal drugs as many that were designed for IFI may well be adapted for superficial infections. In addition, IFI often have cutaneous findings, and dermatologists may be able to treat these with new antifungal drugs. In this review, we discuss the latest advances in antifungal treatments and examine the ways in which dermatologists may benefit from these recent developments.

ME1111
ME1111 is a novel antifungal drug discovered by Meiji Seika Pharma Co., Ltd. that works against dermatophytes. The drug is of small molecular size and works by inhibiting succinate dehydrogenase (complex II), an enzyme involved in mitochondrial respiratory electron transfer and ATP production.4 Currently, it is under clinical development as an onychomycosis treatment, and recent studies have looked into its effectiveness against the fungal nail infection. In 2017, Natsuki et al studied in-vitro permeation of ME1111 through human nail plates after daily application for 14 days compared to other topical antifungal agents for onychomycosis.5 Results showed that the in vitro antidermatophytic efficacy coefficients of ME1111 measured in deep nail layers were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine. With this, the authors concluded that ME1111 has outstanding permeation of human nails.

The effectiveness of ME1111 against dermatophytes as well as its ability to penetrate nails makes the drug a promising treatment for onychomycosis. As an infection that is often difficult for dermatologists to treat, ME1111 could be helpful as a topical treatment, particularly for nearly full-thickness nail plate infections. Oral antifungals, including terbinafine, itraconazole, and fluconazole, are known to be more effective than topical antifungal treatments.6 However, these medications can be associated with liver, cardiac, and renal issues and can interfere with other medications.6 Additionally, it is not uncommon for