Fungi are ubiquitous in the environment but significantly, there are a small number of fungi (~20) that cause >99% of human fungal infections.
Fungal infections are classified broadly into four groups:

• Invasive, life-threatening (e.g. aspergillosis and candidiasis)
• Mucosal (e.g. thrush)
• Skin (e.g. athlete's foot)
• Allergic (e.g. asthma and chronic sinusitis)

F2G is focusing on the life-threatening, invasive fungal infections segment which has risen dramatically over the last 20 years. Today, 4% of all patients dying in modern tertiary care hospitals have invasive aspergillosis (caused by the fungal pathogen Aspergillus spp), and 2% have invasive candidiasis (caused by Candida spp).

Patients at risk of aspergillosis include those with damaged immune systems, including transplant recipients and those with leukaemia. Additionally, patients in intensive care units are at particular risk of candidiasis. The crude mortality from invasive aspergillosis is around 85% and for Candida bloodstream infections is 40%. Response rates following treatment with the currently available drugs however are far from satisfactory as shown below. It is very clear therefore that there is a major clinical need for new drugs.

There are only four classes of established antifungal drugs on the market - polyenes (e.g. amphotericin B), triazoles (e.g. fluconazole and itraconazole), allylamines (e.g. terbinafine) and the newly introduced echinocandins (e.g. caspofungin). Of these classes, only three are used to treat systemic fungal infections.

A new class of antifungal drug, the echinocandins, has recently appeared on the market. The first representative, Merck's Cancidas (caspofungin) was launched early in 2002 for salvage therapy for invasive aspergillosis, for which it showed superiority over amphotericin, but the drug's distinguishing feature is its fungicidal activity against the more common Candida species. Cancidas has peak sales forecasts of $300-$500m. The second echinocandin, Fujisawa's Funguard (micafungin) was launched in 2002 (Japan only) and closely resembles Merck's product. Funguard sold $100m in its first year in Japan alone. Drug formulation remains a problem for the echinocandins as all are administered by intravenous infusion and there is little prospect of developing oral formulations.

The azoles and triazoles have been used since the 1970s, the most successful of which is Pfizer's fluconazole (primary care and tertiary care) that exceeds one billion dollars in sales each year. Pfizer launched a new triazole (voriconazole) to replace its existing drug that came off patent in 2004. Voriconazole is a hospital only drug and is forecast to reach $500m per year in sales. Only the triazoles and terbinafine have oral forms, for which long-term oral prophylaxis in at-risk patients is commonplace. The current intravenous formulation of the triazoles useful for aspergillosis cannot be given to patients with poor renal function, and have limited efficacy. Both routes of administration are important for the ideal treatment of invasive fungal infections. Drug interaction issues are a major impediment to the use of the triazoles; voriconazole, itraconazole and posaconazole. The interactions with cancer chemotherapy agents and immune suppressants are particularly difficult to handle clinically.

Despite the commercial success of the triazoles and the introduction of the echinocandins, mortality of invasive fungal infections remains high, particularly those caused by filamentous fungi. Experience will show if the echinocandins will reduce the mortality of invasive Candida infections to the levels comparable with those for bacterial disease. The high mortality associated with invasive aspergillosis is largely due to none of the currently available drugs being sufficiently cidal.

Based on the sales forecasts of the recently launched echinocandins ($500m per year) and the current sales of a single amphotericin product ($100m per year), F2G believes that a new class of compound with broad spectrum activity against Aspergillus and Candida species could provide sales forecasts >$600m per year and would provide numerous opportunities including lucrative licensing/partnering deals or possible trade sale. F2G plans to develop both oral and intravenous formulations where possible, which could further increase sales forecasts in excess of $1.0 billion.

Back