Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis

March 2020 | Volume 19 | Issue 3 | Original Article | 272 | Copyright © March 2020

Published online March 1, 2020

Emil A. Tanghetti MD,a William Philip Werschler MD,b Edward Lain MD MBA,c Eric Guenin PharmD PhD MPH,d Susan Harris MS,e Anya Loncaric MS,e Radhakrishnan Pillai PhDe

aCenter for Dermatology and Laser Surgery, Sacramento, CA bUniversity of Washington, School of Medicine, Seattle, WA cAustin Institute for Clinical Research, Austin, TX dOrtho Dermatologics, Bridgewater, NJ eBausch Health US, LLC, Petaluma, CA

Abstract
Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies.
Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator’s Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed.
Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P<0.001]; noninflam-matory, -56.0% vs -42.0% [P<0.001]). Treatment success at week 12 was also greater with tazarotene 0.045% lotion versus vehicle (30.4% vs 17.9%; P<0.001). The most frequent treatment-emergent AEs related to tazarotene treatment were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%).
Conclusions: The new tazarotene 0.045% lotion formulated with polymeric emulsion technology demonstrated statistically signifi-cantly superior efficacy versus vehicle and was well tolerated in pediatric and adult patients with moderate-to-severe acne in this pooled analysis of 2 vehicle-controlled phase 3 studies.

J Drugs Dermatol. 2020;19(3):272-279. doi:10.36849/JDD.2020.4869

INTRODUCTION

Topical retinoids remain the mainstay of therapy for acne vulgaris.1 They are, however, associated with skin irritation during the initial weeks of application. Erythema, scaling, dryness, burning, and pruritis of varying severities can occur, depending on the retinoid, dose, and vehicle. These unwanted effects, along with unpleasantly greasy or sticky-feeling formulations,2 can potentially affect comfort and treatment adherence. More importantly, traditional semisolid formulations—such as creams, lotions, and ointments—may not provide an even dispersion of drug onto the skin.2

Among topical retinoids, tazarotene 0.1% has proven to be highly effective both as monotherapy and in combination with other agents. A number of studies have reported that tazarotene markedly reduces both comedonal and inflammatory facial acne lesions.3-15 Although tazarotene may be more effective than other topical retinoids in treating acne,11,16 problems with skin irritation continue to exist with the current approved formulations (gel, foam, cream),17 which may limit its usefulness. The application of tazarotene with a moisturizer appears to improve tolerability without affecting efficacy;18 however, there continues to be an unmet need for a highly effective topical acne medication that has a lower irritability profile than the currently available treatment options.

Polymeric emulsion technology represents a novel approach to developing dermatological products. This technology provides simultaneous delivery of the active ingredient along with solvents, emollients, and humectants—which allows for lower drug concentrations compared to conventional formulations,