Hallux Inc. is a clinical-stage pharmaceutical company focused on developing a new subungual terbinafine dosage form that when administered topically direct to the nail bed is highly effective at curing DLSO. To date, the prescription agents FDA approved for this infection are either low cure rate topical products that must be self-applied daily by patients to their nail plates for at least twelve months or oral medications that are taken once-daily for three months and are associated with systemic side effects.
Hallux is conducting clinical investigation of HSG, a product candidate the company believes may be highly effective and safe for patients with onychomycosis who have had to live with this unsightly and often painful infection for years.
The company’s aim is to secure FDA approval of HSG after demonstrating in clinical trials that the agent eradicates disease causing dermatophytes enabling the regrowth of clear, disease-free nails without reliance on systemic circulation. Initially, Hallux investigated terbinafine micro-inserts that were placed on the nail bed by physician using a special applicator. In 2018, the company changed course to develop a novel, terbinafine subungual gel formulation that should perform better than the solid-micro-inserts when accessing the often hard to reach subungual infection zones.
Hallux completed a phase 2 clinical study with its first subungual dosage form, the solid micro-insert HTS-519, in September 2018. The trial evaluated efficacy, safety, and tolerability in 30 moderate-to-severe onychomycosis patients enrolled from a high-volume podiatric clinic in Arizona. In early 2022, the company began a similar study with HSG which evaluates a longer treatment duration.
THE PROBLEM WITH ONYCHOMYCOSIS
Onychomycosis (tinea unguium) is a fungal infection of the nail bed. It is commonly referred to as ‘toenail fungus’ because toe infections constitute the majority of cases. The infection typically begins as a small yellow or white spot observed on the nail plate that can spread over the years to eventually cover the entire nail plate surface. The diseased toenail also detaches from the nail bed causing further discoloration and dystrophia.
Yellow, Infected, and Ugly Toenails
Onychomycosis is easy to identify as toenails become yellow, thick, and unsightly in appearance. As the fungus in the nail bed proliferates, the resulting damage can cause pain, difficulty in walking and wearing shoes, and social embarrassment due to the ugly appearance of the nails. Untreated onychomycosis may lead to additional serious complications for diabetics, immune compromised patients, and patients with poor circulation.
The primary symptoms of onychomycosis are increasingly thickened toenails that turn discolored and raised from the nail bed.
It is estimated that 35 million Americans suffer from onychomycosis. The fungus, which enters the nail bed from the distal or lateral end, can be contracted from exposure to a range of environments such as gym floors or swimming pools. Socks and shoes create a dark, warm, and moist environment for the fungus to grow.
Despite many attempts by pharmaceutical companies over the years to develop effective remedies for toenail fungus, the few products FDA approved and available today are poor treatment options for two reasons. First, the topical products brushed onto the nail plate have difficulty penetrating to the infected nail bed and cure rates are low. Secondly, the orals like Lamisil® can cause systemic side effects. Liver toxicity and drug interactions, while rare, are of particular concern to patients seeking improvement. The three primary treatments for onychomycosis used today are:
Orals
Lamisil® (terbinafine hydrochloride) is the most common antifungal agent used to treat toenail fungus through an ‘inside-out’ approach. Patients take a 250mg tablet every day for 12 weeks. The medicine travels through the body’s circulatory system and only a fraction of the dose reaches the toenail bed where the infection causing dermatophytes reside. The package insert reports a best-in-class complete cure rate of 38%, but use of the drug is associated with drug-to-drug interactions and other adverse events. Patients must still consent to liver function tests before each prescription can be filled at the pharmacy.
Topicals
Jublia®, Kerydin®, and Penlac® are FDA approved prescription topicals that are brushed by patients onto the top of the toenail every day for a year or more in an effort to get enough drug through to the nail bed to be effective. This approach requires the medicine to penetrate three layers of hard keratinized nail plate to reach the nail bed where the fungus resides and does its damage. As expected, penetrating the nail plate is challenging and in clinical trials the complete cure rates for these products range from 8% to 17%, indicating a failure rate of over 80%. To make matters worse, patients often fail to comply with the absurdly long 12-month daily treatment regimen making any chance of success even less probable. Yet, while complete cure rates are significantly lower than Lamisil®, topical products are still preferred by patients to avoid the systemic risk. This underscores the need for a new topical product that delivers efficacy on the order of Lamisil® without the risk of a systemic adverse event or the burden of having to self-dose your own toes every day for a year or longer.
Toenail debridement
This routine podiatric procedure involves trimming, thinning, and removing as much of the fungus-infected nail and debris under the nail as possible. Podiatrists are reimbursed by Medicare for up to six debridement procedures per year on their patients with onychomycosis. While debridement is helpful, it does not cure the infection which means patients must continue debridement for years without any real relief to their underlying problem. Podiatrists augment debridement by selling patients in-office dispensed OTC topicals like Formula 7 that have not undergone FDA approved clinical trials and therefore cannot make claims regarding the true efficacy of their products in treating onychomycosis.
THE HALLUX SOLUTION
Hallux is focused on the subungual topical treatment of onychomycosis with HSG, a gel administered by a physician in a series of quick and easy in-office applications. The aim is to provide patients with an FDA approved product proven highly effective, safe, reliable, and convenient.
Physician administration of HSG directly to the nail bed enables precise delivery of the potent antifungal drug terbinafine directly to the infection sites where it is needed. Taking the same drug orally requires much greater drug exposure because the delivery path extends through the liver and the body’s systemic circulation before reaching the toenail bed infection site.
Hallux first product was a biodegradable micro-insert that enabled direct, subungual administration of terbinafine at higher concentrations in the nail bed than achieved with oral delivery.
At Hallux Inc., the goal is to develop a subungual topical dosage form that safely delivers high concentrations of terbinafine directly to the nail bed infection site leading to higher rates of complete cure and lower rates of recurrence. In doing so, the company strives to offer patients a significant improvement over existing orals and topicals by eliminating:
- Three months of daily pills
- The potential for systemic side-effects
- The potential for harmful drug interactions
- The frustration of being stuck with an ineffective yet expensive topical medication that is only indicated for mild infections and requires self-application by the patient every day for twelve months or more
The Hallux Micro-Insert HTS-519 completed a phase 2 clinical study in moderate to severe onychomycosis patients in September 2018.