further development of the 5-day regimen of tirbanibulin ointment 1% in treating AK on the face or scalp in Phase 3 studies.
The Phase 1 study was a proof-of-concept study with a doseescalating design in treatment area and treatment duration on the dorsal forearm. AK lesion count was consistently reduced in all cohorts, with the 5-day regimen over 25 cm2 showing the highest complete clearance rate. This 5-day regimen was further evaluated on the face or scalp in the Phase 2 study. Results of the Phase 2 study showed that both 3-day and 5-day regimens had substantial activity against AK, with the 5-day regimen demonstrating numerically higher 100% clearance (43% vs 32%) and sustained response at 12 months post-day 57 (43% vs 30%) than the 3-day regimen. Although both studies were small and uncontrolled, complete AK clearance rates of tirbanibulin ointment 1% at day 57 for the 5-day regimen over 25 cm2 on the face/scalp or dorsal forearm align well with topical treatment like ingenol mebutate (face/scalp, 42%; trunk/extremities, 32%) administered over 2-3 days.20
The favorable safety profile of tirbanibulin ointment was supported by the paucity of systemic, severe, or serious side effects and minimal systemic absorption. Although tirbanibulin ointment did cause some local irritation, it induced mostly mild and transient erythema, flaking/scaling, pruritus, and pain that resolved quickly and spontaneously. The low incidence of severe LSRs and LSRs of greater concern (vesiculation/pustulation and erosions/ulceration) that distinguishes tirbanibulin ointment 1% from other approved topical AK treatments warrant evaluation in future studies.
In summary, these Phase 1/2 studies supported our hypothesis that tirbanibulin ointment 1%, given as a short, once-daily treatment for AK lesions on the forearm, face, or scalp, could reduce lesions and is well tolerated with low-grade LSRs that quickly resolve without intervention. This allowed the 5-day treatment regimen of tirbanibulin ointment 1% to be selected for efficacy and safety evaluation in two double-blinded, placebocontrolled, randomized, parallel-group, multicenter, Phase 3 trials for AK on the face/scalp.
The Phase 1 study was a proof-of-concept study with a doseescalating design in treatment area and treatment duration on the dorsal forearm. AK lesion count was consistently reduced in all cohorts, with the 5-day regimen over 25 cm2 showing the highest complete clearance rate. This 5-day regimen was further evaluated on the face or scalp in the Phase 2 study. Results of the Phase 2 study showed that both 3-day and 5-day regimens had substantial activity against AK, with the 5-day regimen demonstrating numerically higher 100% clearance (43% vs 32%) and sustained response at 12 months post-day 57 (43% vs 30%) than the 3-day regimen. Although both studies were small and uncontrolled, complete AK clearance rates of tirbanibulin ointment 1% at day 57 for the 5-day regimen over 25 cm2 on the face/scalp or dorsal forearm align well with topical treatment like ingenol mebutate (face/scalp, 42%; trunk/extremities, 32%) administered over 2-3 days.20
The favorable safety profile of tirbanibulin ointment was supported by the paucity of systemic, severe, or serious side effects and minimal systemic absorption. Although tirbanibulin ointment did cause some local irritation, it induced mostly mild and transient erythema, flaking/scaling, pruritus, and pain that resolved quickly and spontaneously. The low incidence of severe LSRs and LSRs of greater concern (vesiculation/pustulation and erosions/ulceration) that distinguishes tirbanibulin ointment 1% from other approved topical AK treatments warrant evaluation in future studies.
In summary, these Phase 1/2 studies supported our hypothesis that tirbanibulin ointment 1%, given as a short, once-daily treatment for AK lesions on the forearm, face, or scalp, could reduce lesions and is well tolerated with low-grade LSRs that quickly resolve without intervention. This allowed the 5-day treatment regimen of tirbanibulin ointment 1% to be selected for efficacy and safety evaluation in two double-blinded, placebocontrolled, randomized, parallel-group, multicenter, Phase 3 trials for AK on the face/scalp.
DISCLOSURES
Steven Kempers has no conflicts of interests to disclose. Janet DuBois has received investigator fees for her institution from Aclaris Therapeutics, Inc., Allergan, Inc., BioPharmX, Botanix Pharmaceuticals, Brickell Biotech, Inc., Cara Therapeutics, Dermata Therapeutics, Dermavant Sciences, Dermira, Inc., Dr Reddy’s Laboratories, Endo International plc., Escalier Biosciences, Foamix Pharmaceuticals Ltd., Galderma, GlaxoSmithKline, Glenmark Generics Inc., LEO Laboratories Ltd., Moberg Pharma North America LLC, MOE Medical Devices LLC, Novan, Inc., Perrigo Company plc, Pfizer Inc., Naked Biome Inc., Novartis Pharmaceuticals Corp., SeegPharm SA, Sienna Biopharmaceuticals, Inc., Sol-Gel Technologies Ltd., Taro Pharmaceutical Industries Ltd., Therapeutics Inc., and Valeant Pharmaceuticals North America LLC. Seth Forman has received consultancy fees from AbbVie and Dermira, Inc., and principal investigator fees from Pfizer Inc. He has also received grants/research funding for his role as a principal investigator for AbbVie, AstraZeneca plc, Celgene Corporation, Cutanea Life Sciences, Eli Lilly Company, Incyte Corporation, Innovaderm Research Inc., Novartis, Promius Pharma, LLC., Regeneron Pharmaceuticals, Inc., and Valeant Pharmaceuticals North America LLC. Seth Forman has received honoraria from AbbVie (advisory board), Eli Lilly Company, and Novartis (speaker). Amy Poon is a former employee of Athenex, Inc., and may own stock/stock options in Athenex, Inc. Eva Cutler is an employee of Athenex, Inc. Hui Wang is an employee of Athenex, Inc., and may own stock/ stock options in Athenex, Inc. David Cutler is an employee of Athenex, Inc., and may own stock/stock options in Athenex, Inc. Jane Fang is a consultant of Athenex, Inc., and may own stock/ stock options in Athenex, Inc. Rudolf Kwan is an employee of Athenex, Inc., and may own stock/stock options in Athenex, Inc.
Funding source: These studies were funded by Athenex, Inc., Buffalo, NY, USA. Athenex, Inc. was responsible for the design and conduct of the studies, as well as the collection, management, analysis, and interpretation of the data.
Funding source: These studies were funded by Athenex, Inc., Buffalo, NY, USA. Athenex, Inc. was responsible for the design and conduct of the studies, as well as the collection, management, analysis, and interpretation of the data.
ACKNOWLEDGMENT
Investigator of the Phase 1 study: Michael Jarratt, MD. Investigators of the Phase 2 study: Michael Jarratt, MD, Elizabeth Hughes-Tichy, MD; Nancy Krywonis, MD; Judith White, MD; Timothy Jochen, MD; Suzanne Bruce, MD; Terry Jones, MD; J. Scott Overcash, MD; Javier Alonso-Llamazares, MD; Christina Feser, MD; Todd Schlesinger, MD; Jeffrey Rosen, MD; Sunil Dhawan, MD; J. John Goodman, MD; and Athenex, Inc. consultant, Edwin Peets, PhD.
Medical writing support, under the direction of the authors, was provided by Gemma McGregor, PhD, of CMC AFFINITY, McCann Health Medical Communications, in accordance with Good Publication Practice (GPP3) guidelines. This assistance was funded by Almirall, S.A., Barcelona, Spain.
Medical writing support, under the direction of the authors, was provided by Gemma McGregor, PhD, of CMC AFFINITY, McCann Health Medical Communications, in accordance with Good Publication Practice (GPP3) guidelines. This assistance was funded by Almirall, S.A., Barcelona, Spain.
REFERENCES
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2. Richard MA, Amici JM, Basset-Seguin N, Claudel JP, Cribier B, Dreno B. Management of actinic keratosis at specific body sites in patients at high risk of carcinoma lesions: expert consensus from the AKTeam of expert clinicians. J Eur Acad Dermatol Venereol. 2018;32(3):339-346.
2. Richard MA, Amici JM, Basset-Seguin N, Claudel JP, Cribier B, Dreno B. Management of actinic keratosis at specific body sites in patients at high risk of carcinoma lesions: expert consensus from the AKTeam of expert clinicians. J Eur Acad Dermatol Venereol. 2018;32(3):339-346.
