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 plus flucytosine. 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.