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 , William Philip Werschler , Edward Lain , Eric Guenin , Susan Harris , Anya Loncaric , Radhakrishnan Pillai

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

(26.8%) and 151 patients (19.1%) in the 0.045% tazarotene and vehicle groups, respectively. Of the patients who reported any TEAE, more than 95% reported only AEs of mild or moderate severity (tazarotene, 95.2%; vehicle, 97.4%). In the tazarotene arm, 88 patients (11.3%) reported AEs that were deemed treatmentrelated; the most common were application site pain (5.3%), dryness (3.6%), exfoliation (2.1%), and erythema (1.8%). Of the 8 participants who reported serious AEs during the study (n=4 in each treatment group), none were deemed related to treatment. Among AEs leading to study discontinuation in the tazarotene arm, the most common were application site pain (13 [1.7%]) and application site erythema (6 [0.8%]). Details regarding cutaneous safety and tolerability have been reported.22 Briefly, in the tazarotene-treated group, mean cutaneous safety and tolerability ratings were all between none (0) and mild (1) at weeks 4, 8, and 12. By week 12, any slight, transient increases in cutaneous safety and tolerability had returned to baseline values or improved (Figure 5).

DISCUSSION

Based on decades of clinical experience, multiple consensus guidelines recommend topical retinoids, either as monotherapy or in combination with other agents, for treating acne vulgaris.23,24 However, irritating side effects—which may vary depending on the type and dosage of the active ingredient, as well as vehicle characteristics—can limit their use and negatively impact patient adherence.25,26 To alleviate these bothersome side effects, patients may try to apply a moisturizer along with their topical retinoid, but this approach does not guarantee that active ingredient(s) will be evenly dispersed onto the skin.

Studies to date suggest that tazarotene 0.1% in gel, foam, or cream formulation may have the greatest efficacy among topical retinoids and appears effective in reducing postinflammatory hyperpigmentation.11,16 Unfortunately, tazarotene 0.1% formulations may also have the potential for the greatest cutaneous irritation.27 Among these various formulations, the 0.1% foam may have some advantages over gels and creams, which have been reported to leave a sticky residue and can be difficult to apply evenly.28 Patient preference data for this formulation is lacking, and clinical benefits appear similar to those of other randomized, double-blind studies of tazarotene 0.1% cream and gel,9,29 with treatment emergent AEs including application site irritation, dryness, and erythema still common, particularly in the first four weeks of treatment.

To maintain the proven efficacy of tazarotene while improving its irritability profile, a unique formulation of tazarotene 0.045% lotion was developed utilizing a new polymeric matrix technology. This is the first acne treatment with a reduced tazarotene concentration relative to standard 0.1% formulations. With polymeric matrix technology, uniform and simultaneous distribution of tazarotene, humectants, and emollients can be delivered in a lightly moisturizing and aesthetically pleasing lotion formulation. As a result, this new lower-dose formulation provides optimal delivery of tazarotene into epidermal layers, thereby maintaining efficacy while reducing local irritation.21

In the current pooled analysis, tazarotene 0.045% lotion significantly reduced both inflammatory and noninflammatory lesions relative to vehicle at week 12. Treatment success was achieved in 30.4% of patients at that time point. Notably, tazarotene 0.045% lotion was also well tolerated, with the most common treatmentrelated AEs being application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). These rates compare favorably with those previously reported for tazarotene 0.1% cream and gel formulations (irritation: 3.5% to 13%;7-9,13-15 burning: 1% to 14%; 7-10,14,15 dryness, 1% to 27%;7-11,13-15 exfoliation, 1% to 29%).5,7-10,12,14,15 Application site reactions were generally less frequent than those previously reported for tazarotene 0.1% gel, cream, or foam, possibly as a result of the novel formulation and/or lower tazarotene concentration, although these data are difficult to compare in the absence of head-to-head trials. Overall AE rates were also low, with favorable tolerability, which may improve patient adherence.

CONCLUSION

Utilizing polymeric emulsion technology, a novel tazarotene formulation— with less than half the concentration of other available tazarotene products for acne—is effective and well tolerated in this pooled analysis of two phase 3 studies. Compared to other tazarotene formulations approved for treatment of moderate-tosevere acne, this new formulation offers significant tolerability benefits (without sacrificing efficacy) by allowing simultaneous delivery of tazarotene, humectants, and moisturizers.

DISCLOSURES

Dr. Emil Tanghetti has served as speaker for Novartis, Ortho Dermatologics, Sun, Lilly, Galderma, AbbVie, and Dermira; served as a consultant/clinical studies for Hologic, Ortho Dermatologics, and Galderma; and is a stockholder for Accure. Dr. William Philip Werschler has served as an investigator for Ortho Dermatologics. Dr. Edward Lain has served as an investigator/ consultant or speaker for Ortho Dermatologics. Dr. Eric Guenin is an employee of Ortho Dermatologics and may hold stock and/ or stock options in its parent company. Dr. Radhakrishnan Pillai, Susan Harris, and Anya Loncaric are employees of Bausch Health US, LLC and may hold stock and/or stock options in its parent company. Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC.

ACKNOWLEDGEMENTS

Medical writing and editorial support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC.