INDIVIDUAL ARTICLE: VEHICLES ALWAYS MATTER

Over the past several years, the field of acne treatments, which had been relatively unchanged, has welcomed a variety of innovations. From new molecules and mechanisms of action to previously implausible fixed combination products, prescribers have more topical treatment options than ever before. Compared to predecessor treatments, new drugs may offer enhanced efficacy and tolerability, fewer side effects, reduced risk for problems like antibiotic resistance, and more patient convenience. We as clinicians must recognize these advantages that some of the newest drugs confer.

However, while medicinal chemists and formulators had been toiling in labs, the FDA was at work modifying the requirements for demonstrating acne treatment efficacy!!! They set such a high bar that requires drugs to demonstrate both that a proportion of patients achieve clear or almost clear skin and that patients also have at least a 2-grade improvement in acne severity (both as measured by Evaluator’s Global Severity Score or Investigator Global Assessment or Physician Global Assessment ) from baseline. Previously, treatment success was demonstrated by either clear or almost clear skin or at least a 2-grade improvement from baseline but NOT both.

This dual assessment of treatment success helps to reduce reliance on inflammatory and non-inflammatory acne lesion counts as the only primary endpoint. While these counts are important and meaningful, there are well-identified challenges associated with the objective measure and classification of lesions.¹ (Recall, too, that overwhelming evidence shows that all acne is inflammatory. ² Thus, binary classification of acne lesions is misleading.) In reality, most of us do not count acne lesions in a clinical practice setting; rather, we often assess the severity of the disease based on a gestalt impression.

With this understanding of acne treatment trials in mind, one can assess the significance of a relatively new triple combination, fixed-dose topical gel for acne treatment. As always, vehicles matter. In the case of a combination of clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% gel, the first triple combination for acne, adapalene, and benzoyl peroxide are micronized and distributed in a polymeric gel to facilitate even distribution and delivery into the pilosebaceous unit.^3,4

What is particularly striking about this formulation, as discussed in the pages ahead, is the proportion of subjects who achieved treatment success and the implications for patient management. The phase II trial assessed the triple combination, as well as marketed dyad gel combinations, and vehicle gel with only about 150 subjects in each arm of the five-arm study, making it very challenging to reach statistical significance for the triple combination. Despite that, the proportion of patients who achieved treatment success with the triple combination was significantly greater than any of the dyad gels. In phase 3 clinical trials, just over half of the participants achieved treatment success (at least a 2-grade improvement in EGSS and rated clear or almost clear) at week 12 with triple combination gel. This treatment success rate was higher than for any other topical treatment assessed to date in a phase 3 clinical trial although we don’t scientifically compare separate clinical trials.⁵

With more treatment options than ever, dermatology providers can create customized treatments for their patients with the potential for better outcomes and patient experiences. The unique, first-of-its-kind, topical triple combination of clindamycin, benzoyl peroxide, and adapalene fixed dose gel represents a once-daily convenient therapy with demonstrated enhanced clinical trial efficacy and a favorable tolerability profile, thanks to its novel vehicle.

Therefore, “VEHICLES ALWAYS MATTER”.

Leon Kircik MD
Clinical Professor of Dermatology; Icahn School of Medicine at Mount Sinai, New York, NY; Adjunct Clinical Professor of Dermatology; Indiana University School of Medicine, Indianapolis, IN; Medical Director, Physicians Skin Care, PLLC Louisville, KY; DermResearch, PLLC Louisville, KY, Skin Sciences, PLLC Louisville, KY