The world market for antifungal agents is currently worth in excess of US$6 billion with consistent annual growth driven by year on year increases in the susceptible immune compromised patient population. Increases in cancer, organ transplants and use of potent drugs, including broad spectrum antibiotics has led to significant increases in fungal infections. Fungi are now recognised as a major issue in several respiratory conditions being responsible for exacerbations of symptoms in asthma, COPD and bronchiectasis patients. This is likely to increase the use of antifungal drugs over the coming years.
There are only three major drug classes, triazoles, polyenes and, echinocandins. The polyenes have been available for over 50 years and the introduction of amphotericin B in the 1960’s radically changed the survival hopes of patients with serious fungal infections. The azoles brought the possibility of oral treatment and have shown better tolerability overall than the polyenes. The echinocandins are the latest class of agent to be introduced to the market, but there has not been a new class of agents for over 15 years.
Crude mortality remains high amongst haemato-oncology and intensive care patients and increasing resistance is being seen amongst Candida and Aspergillus species. The mechanisms for this may be partly due to overuse of antifungals, but with Aspergillus species two main mechanisms have been identified; one is chronic use in respiratory patients where it is almost impossible to clear the infection, and the second is acquisition of strains which have developed resistance due to the use of azoles in agriculture. Other rare moulds such as the Zygomycetes, Scedosporium and Lomentosporum species are also becoming more prevalent, are challenging to differentiate from aspergillosis and can be difficult to treat.
Other pathogens such as Coccidioides species are endemic to particular parts of the world and can be contracted by otherwise healthy individuals, causing chronic debilitating disease. Olorofim has activity in vitro and in animal models, against a wide range of endemic mycoses, including Coccidioides species and may offer an alternative to the currently-available agents.
F2G believes that its novel agent, olorofim, and subsequent agents, will address some of the many challenges which face the treating physician and the patient with invasive fungal infections.