A silicone-based gel with a nitric oxide platform has been found to be safe and efficacious for treating tinea pedis, according to the results of a Phase 2 trial.
The drug candidate SB208 from Novan Inc. is a broad-spectrum antifungal gel.
“This is the first time we have a topical antifungal that is based on a nitric oxide platform, which is naturally found in our system,” says Leon Kircik, M.D., a clinical associate professor of dermatology at Icahn School of Medicine at Mount Sinai in New York City and Indiana University Medical Center in Indianapolis. “Nitric oxide exerts its antifungal activity against a broad spectrum of fungal species including T.rubrum, through inactivation of cellular enzymes, disruption of cellular respiration and lipid peroxidation.”
Dr. Kircik says the study results are better than he expected, “but there are no real surprises. Therapy was very tolerable. There were no significant irritation signals.”
The double-blind, randomized, vehicle-controlled, dose-ranging clinical trial recruited 222 individuals.
Inclusion criteria were patients between the ages of 18 to 70 with a clinical diagnosis of tinea pedis on one or both feet either localized to the interdigital spaces or predominately interdigital with possible extension to other areas of the foot.
The presence of athlete’s foot was confirmed at baseline by a positive potassium hydroxide (KOH) wet mount for segmented fungal hyphae on a skin scraping from the target lesion and with a positive fungal culture.
In addition, the sum of the clinical signs and symptoms scores of the target lesion was at least 4, with a minimum score of 2 for erythema and a minimum score of 2 for scaling or pruritus (on a scale of 0 to 3 where 2 indicates moderate severity).
The four arms of the study were 16% gel, 4% gel, 2% gel and placebo gel, all administered once daily at home.
Two weeks of treatment was followed by a four-week post-treatment observation period.
Besides endpoints of safety and tolerability, the clinical trial assessed mycological cure, which was defined as negative KOH and negative fungal culture at week two (the end of treatment).
The former is a lab test “that places KOH on a scrap of nail and then is examined under a microscope,” Dr. Kircik says. “If there is hyphae, that means there is fungus.”
Dr. Kircik says it is important that both tests are negative to ensure that the fungus is dead.
“Sometimes, the hyphae remains but the fungus is dead,” he says. “However, that would be considered a study failure because you must achieve both negative KOH and negative culture.”
The primary efficacy end point of negative fungal culture at week two was attained in 61.3% of patients treated with SB208 2%, in 80.6% of patients treated with 4% concentration and 74.2% with 16% concentration. This compared to 45.5% of patients treated with placebo.
“It is unlikely that Novan will offer a 2% concentration, as the more potent formulations fared better,” Dr. Kircik says.
Mycological cure was also maintained at six weeks for both doses.
“This tells us that this is a potent drug, even four weeks after stopping treatment,” says Dr. Kircik, medical director of Skin Sciences PLLC in Louisville, KY.
However, Dr. Kircik anticipates that the antifungal drug will not become commercially available for the next couple of years.
More uses considered
Meanwhile, Novan expects later this year to begin a Phase 2 trial of SB208 to treat onychomycosis, a chronic fungal infection of the nails that affects more than 40 million Americans, according to a company estimate.
“People who have tinea pedis often have onychomycosis as well, and vice versa,” Dr. Kircik says.
The study’s targeted enrollment is 300, comparing two doses and a vehicle.
“Most of the topical antifungals for onychomycosis have not been successful,” Dr. Kircik says. “This is not because the antifungals do not kill the fungus, but that these antifungals are unable to penetrate the nail plate. The nail plate is extremely difficult to penetrate.”
In contrast, because SB208 is a gas formulated in a gel, “it can readily penetrate the nail plate reaching the site of infection.” Dr. Kircik says.
If future studies of SB208 pan out, “we will have a topical that can be used to treat both tinea pedis and onychomycosis at the same time, which will be a great contribution to our armamentarium of topical antifungals,” Dr. Kircik says.
Disclosure: Dr. Kircik is a consultant, investigator and on the advisory board of Novan.