Acne is a common, complex skin disorder most people experience at some point in their lives. While many treatments are currently available, options for severe acne are limited. Additionally, clinicians are aiming to reduce long-term broad-spectrum antibiotic use, which is becoming less effective as antibiotic resistance becomes more common.
Possible solutions? More effective topical treatments and targeted therapies. Here are seven of the most promising products currently in development.
1. Topical Adapalene / Benzoyl Peroxide
While topical treatments have not traditionally been effective for severe acne management, this once-daily gel combination of a retinoid and benzoyl peroxide (BP) may change that. In one recent 12-week Phase III trial, over a third of patients achieved Investigator’s Global Assessment (IGA) success compared to 11 percent treated with vehicle. In addition, patients saw a 68 percent reduction in inflammatory lesion count compared to 37 percent with the vehicle.
2. Micronized Benzoyl
Peroxide / Lipohydroxy Acid
In contrast to BP alone, when combined with lipohydroxy acid (LHA), it is able to penetrate the pilosebaceous unit. LHA is a derivative of salicylic acid containing a long-chain fatty acid. This makes the molecule more lipophilic with a much greater ability to penetrate intercellular spaces. One recent study found that combination therapy with BP/LHA and tretinoin to be as effective in reducing inflammatory and non-inflammatory acne lesions as BP/clindamycin gel and tretinoin.
3. Cortexolone 17 Alpha-Propionate
While anti-androgens are well-known for their ability to reduce sebum production and acne severity, systemic treatments are restricted to use in female patients and can come with significant side effects. Cortexolone 17 alpha-propionate is a topical anti-androgen currently being researched as an acne treatment for both men and women. One pilot study with male patients showed a decrease in acne lesions over both placebo and tretinoin cream controls.
4. Topical Minocycline
Oral minocycline is a popularly prescribed and effective acne treatment, but it’s one associated with severe side effects. As such, multiple topical formulations of the drug able to penetrate the epidermis and pilosebaceous unit are being developed.
Clinical trials of minocycline 4% foam (FMX 101) found greater than 70 percent reductions in both inflammatory and noninflammatory lesions at 12 weeks. Recent Phase III trials have, however, found the product to be less efficacious, failing to meet its co-primary endpoints in one of the two trials conducted.
5. Acetyl Coenzyme A Carboxylase Inhibitors
One acetyl CoA-carboxylase inhibitor, a prodrug of 5-tetradecyloxy-2-furoic-acid (TOFA), reduces synthesis of sebum lipids in vitro and shrinks sebaceous gland size in the hamster ear model. One early phase clinical study found that the drug reduced lesion counts by 64 percent, compared to 46 percent with the vehicle.
6. Melanocortin Receptor Antagonists
Melanocortin-1 and -5 receptors are expressed in sebaceous glands. One dual antagonist has been shown to inhibit sebocyte differentiation in vitro and to reduce sebum production in human skin transplanted to immunodeficient mice. However, melanocortin antagonists have yet to demonstrate clinical efficacy in the treatment of acne.
7. Nitric Oxide
While an effective anti-inflammatory and anti-microbial agent, previous attempts at applying nitric oxide to dermatological conditions were limited by available delivery systems due to its normally gaseous state. Recently, nitric oxide-release nanoparticles have been shown to inhibit the bacteria-stimulated inflammatory cascade associated with acne with minimal toxicity to keratinocytes.
In one Phase II trial, nitric oxide delivery system SB204 was found to reduce sebum production in patients. However, recently released Phase III replicate pivotal trials reported conflicting results. While one study found a statistically significant improvement over the vehicle control in all three co-primary endpoints, the other observed this in just one. Plans to continue development of SB204 were announced in March with a target date for new drug application submission to the FDA in early 2018.
If you’d like to know more about these and other emerging acne treatments, along with information about disease pathogenesis and standard therapies, be sure to read our recent white paper What’s New in Acne.