Trifarotene Cream (Aklief)
November 15, 2019 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a retinoid topical cream for the treatment of acne. Trifarotene selectively targets retinoic acid receptor gamma (RAR gamma), the most common retinoic acid receptor in the skin, which may reduce topical side effects. It is distributed as Aklief.
INDICATIONS
Trifarotene should be prescribed for the topical treatment of acne vulgaris in patients ≥ 9 years of age.1
DOSAGE
The recommended dose is a thin layer applied to the affected areas of the face and/or trunk once daily in the evening.1 Trifarotene cream will be available as a 0.005% cream in a 30 g pump, 45 g pump, and 75 g pump. Generally, one actuation of the pump is sufficient for the face and two actuations for the upper trunk (upper back, shoulders, and chest).
POTENTIAL ADVANTAGES
Trifarotene is the first retinoid product that is selective for RAR gamma and approved for both facial and truncal acne.2
POTENTIAL DISADVANTAGES
Skin irritation is the primary adverse reaction.1 The frequency of moderately severe reactions, including erythema, scaling, dryness, and stinging/burning, varies from 21-30% for the face and 11-19% for the trunk compared to 4-7% and 2-4% for the vehicle, respectively.1 Exposure to sunlight and sunlamps should be avoided or minimized with sunscreens. Protective clothing is recommended if exposure is unavoidable.
COMMENTS
The efficacy of trifarotene cream was evaluated in two randomized, double-blind, vehicle-controlled, 12-week trials with identical designs.1,3 Subjects exhibited moderate acne on their faces and trunks. Moderate facial acne was defined as ≥ 20 inflammatory lesions and ≥ 25 noninflammatory lesions (score of 3 on a five-point Investigator’s Global Assessment [IGA] scale). Moderate truncal acne was defined as ≥ 20 inflammatory lesions and 20 to < 100 noninflammatory lesions in area reachable for self-application (Physician’s Global Assessment [PGA] scale score of 3 on the trunk).2 The three coprimary efficacy endpoints were rate of success (defined as percent achieving IGA/PGA of clear [0] or almost clear [1] and at least a two-point change from baseline at week 12), mean absolute change in facial and truncal inflammatory, and noninflammatory lesion count from baseline. The intent-to-treat analysis for the face included 612 subjects randomized to trifarotene cream and 596 subjects to a vehicle cream in study 1 and 602 and 610, respectively, for study 2. Trunk results included 600 and 585 subjects for study 1 and 598 and 609 subjects for study 2. In both studies, IGA and PGA scores were significantly better for patients on trifarotene compared to those on the vehicle (P < 0.001). Reductions in inflammatory and noninflammatory lesions occurred more often with trifarotene. Onset of effect in terms of reduction in inflammatory and noninflammatory lesions were seen as early as week 1 for the face and week 2 for the trunk.3 In a long-term, open-label, single-arm, safety and efficacy study (n = 453), trifarotene success continuously improved over 52 weeks.4 Subjects were advised to apply trifarotene for the first 12 weeks and discontinue if success was achieved. IGA success rate improved from 26.6% at week 12 to 65.1% at week 52. The corresponding PGA success rates were 38.6% and 66.9%, respectively. Trifarotene appears to be well tolerated, as 76.5% of subjects completed the study; 3.5% of subjects discontinued the study due to treatment-emergent adverse events.4
CLINICAL IMPLICATIONS
Acne is a common condition among adolescents and adults, affecting about 50 million people in the United States.5 The recommended first-line treatment for moderate acne, according to the American Academy of Dermatology, includes a topical combination of benzoyl peroxide (BP) and antibiotic, retinoid + BP, or retinoid + BP + antibiotic.6 Retinoids have different binding affinities to retinoic acid receptors subtypes. For example, tretinoin binds to alpha, beta, and gamma, while tazarotene and adapalene bind to beta and gamma subtypes. Trifarotene is unique with its selective binding (only to the gamma receptor). It is the first retinoid approved for both face and trunk acne. Trifarotene is unique with its selective binding to the gamma receptor and is the first retinoid approved for both face and trunk acne. The cost for trifarotene is $554.25 for a 45 g pump (size currently available).
REFERENCES
- Galderma Laboratories, LP. Aklief Prescribing Information, October 2019. Available at: http://bit.ly/2pRy6wY. Accessed Oct. 24, 2019.
- Galderma Laboratories, LP. Galderma receives FDA approval for Aklief® (trifarotene) cream, 0.005%, the first new retinoid molecule for the treatment of acne in over 20 years, Oct. 4, 2019. Available at: https://prn.to/2MJb7gA. Accessed Oct. 24, 2019.
- Tan J, Thiboutot D, Popp G, et al. Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne. J Am Acad Dermatol 2019;80:1691-1699.
- Blume-Peytavi U, Fowler J, Kemény L, et al. Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-gamma selective topical retinoid, in patients with moderate facial and truncal acne. J Eur Acad Dermatol Venereol 2019; Jul 15. doi: 10.1111/jdv.15794. [Epub ahead of print].
- American Academy of Dermatology. Acne Clinical Guideline. Available at: http://bit.ly/2Pgfr8H. Accessed Oct. 24, 2019.
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945-973.
Trifarotene should be prescribed for the topical treatment of acne vulgaris in patients ≥ 9 years of age.
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