Novel acne gel found safe in three clinical trials

July 17, 2017

A nitric oxide-releasing gel to treat acne vulgaris has been found to be extremely safe, according to three Phase 1 pharmacokinetic clinical trials.

Dr. StaskoA nitric oxide-releasing gel to treat acne vulgaris has been found to be extremely safe, according to three Phase 1 pharmacokinetic clinical trials presented in April at the annual meeting of the Society for Investigative Dermatology in Portland, Oregon.

SB204 gel is a topical nitric oxide-drug candidate in development by Novan Inc. The active pharmaceutical ingredient is NVN1000, the company’s new chemical entity.

“Our gel has the potential to offer a totally new mechanism of action for acne disease,” says Nathan Stasko, PhD, co-founder, president and chief scientific officer of Novan. “The understanding of acne physiology is finally attaining the level of science and attention it deserves.”

Dr. Stasko says for many decades now, there has been the same themes and types of products for treating acne. “Today, though, is a really important time in the acne space for patients because much of the same innovation that has occurred in psoriasis and atopic dermatitis is now being directed to acne,” Dr. Stasko tells Dermatology Times.

One of the main new features of the acne gel is that nitric oxide has the potential to inhibit the NLRP3 inflammasome assembly and the downstream production of cytokines.

“There are key cytokines in acne, like IL-1β, which have been shown to be the driving force in clogging the pores,” Dr. Stasko says. “We thought that if you could stop that process – the underlying inflammation – then you could possibly treat the disease in an entirely new way.”

Dr. Stasko notes that retinoids have previously attacked this particular component of acne pathology. “However, retinoids accomplish this partly by shedding or peeling off the skin, from a top-down perspective,” he says.

In contrast, nitric oxide remodels the skin from the bottom up, “in a much safer and gentler approach to treat the microcomedones,” Dr. Stasko says.

The series of three safety clinical trials assessed the pharmacokinetics of the acne gel in subjects with acne.

“The goal of these pharmacokinetics studies was to determine if there was any systemic exposure to the product, when applied liberally to a large surface area like the upper chest, the upper back, the face and the shoulders,” Dr. Stasko explains. “In other words, is the drug still safe when administered in a maximal use setting and is there any detectable exposure to the drug in the blood.”

Several sophisticated analytical methods were developed by Novan to help clarify safety of the acne gel, according to Dr. Stasko.

“The conclusion from all three of the studies is that there was no detectable analyte of our drug substance in any of the subjects at any of the time points, under maximal use conditions,” Dr. Stasko says.

Next: Study details

 

The first of the three studies was conducted in 18 adults with moderate to severe acne, for which the gel was applied twice daily for 5 days. The placebo-controlled trial found no evidence of detectable systemic exposure and there were no changes in systemic nitrate levels from pretreatment or between the vehicle and active treated.

“We used nitrate as a marker for nitric oxide exposure,” Dr. Stasko says. “The active gel had a similar level of nitrate as the placebo.”

The second safety study recruited 18 adolescents with acne, for which the gel was applied only once daily for 21 days. Like the first study, the non-placebo controlled trial showed no detectable exposure to the drug’s active ingredient and that nitrate exposure on day 1 was not substantially different from day 21.

The third study assessed cardiovascular safety. Consisting of 48 adults with acne, the trial tested both a therapeutic dose of 4% concentration and a much higher dose of 12% concentration. There was also a placebo and positive control (moxifloxacin, which is known to induce minor cardiovascular changes).

All four arms of the study applied treatment only once, and patients were monitored at several intervals over the first 24 hours.

“Our gel had no effect on any of the cardiovascular parameters at either concentration,” Dr. Stasko says. “There was also no difference, again, in systemic nitrate levels that float throughout the body, in any of the treatment groups.”

The prescription-only acne gel, in a once-daily formulation at a planned 4% concentration, is expected to become commercially available in 2019. The gel could also represent Novan’s first product to market and the first ever nitric oxide-based drug to be approved for dermatology.

“Unlike some current acne products, SB204 has shown really good cutaneous tolerability, is non-irritating, and does not require application twice a day,” Dr. Stasko says.

The company plans to position the gel as first-line therapy for mild to moderate acne, that could also be included as part of a regimen of existing first-line treatments.

Disclosure: Dr. Stasko is co-founder, president and CEO of Novan Inc.