EV-086 for Topical Fungal Infections

About Topical Fungal Infections

Topical fungal infections are common and increasing in frequency. One of the most prevalent topical fungal infections is Onychomycosis (fungal infection of the nail). This infects up to 1 in 8 adults. Onychomycosis is characterised by nail discoloration and thickening and separation of the nail plate from the nail bed. Normally it is not life threatening, but it can cause social embarrassment and, in some cases, pain. Diabetic patients and other risk groups have a greater risk of serious complications from the disease, sometimes necessitating limb amputations.

Current Treatments

Onychomycosis can be treated either orally or topically. Current oral treatments are reasonably effective in 30–60% of patients. However, months of therapy are required, and there is a risk of serious liver toxicity, which is undesirable in non life-threatening infections. Terbinafine (Lamisil™, Novartis, 2007 sales $595 million) and Itraconazole (Sporanox™, Johnson & Johnson) are the leading oral compounds for the treatment of Onychomycosis.

Preferably, topical fungal infections would be treated using topical administration since topical products are inherently much safer than oral treatments. However, existing topical treatments for Onychomycosis typically have poor efficacy – in large part due to poor penetration to the nail bed. The only FDA approved topical treatment is Penlac™, which has a less than 10% clinical cure rate (and following “cure”, there is a greater than 25% recurrence rate). Because of the twin issues of low efficacy (topicals) or toxicity (orals), many sufferers currently do not take any treatment at all and hence effective topicals can potentially expand the market significantly.

A few new compounds and several delivery systems are in development for this market. New compounds include those from Anacor, York, NovaBiotics and NanoBio. Delivery systems and devices range from lasers and high speed particle guns to iontophoretic systems and specific formulations. Companies working on them include Dow Pharmaceutical Sciences and Power Paper Ltd.

How EV-086 May Benefit Patients

The high potency of EV-086 should mean that less compound will need to be delivered across or around the nail to achieve a given level of efficacy compared to current products. In-vitro studies have shown EV-086 to be fast-acting and cidal (i.e., it kills the fungi rather than just inhibiting its growth). These features should also enable shorter dosing regimens, easier compliance and a lower relapse rate. EV-086 could also offer an efficacious topical treatment regime as an alternative to the existing oral treatments, but without their associated toxicity.

Current Development Status

EV-086 is in pre-clinical development. It has shown efficacy in pre-clinical studies after topical administration in models of topical skin dermatophytosis. Evolva has designed several prototype formulations that will be prepared and plans to initiate testing in Phase I clinical studies in 2010.