CFAD V. Anacor, |PR201 5-01 776
`ANACOR EX. 2159 - “I/“IO
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 1/10
`
`

`
`
`JANUARY 2016 ISSUE 1 4 VOLUME 15 '
`
`
`
`
` I JOURNAL OF DRUGS IN DERMATOLOGY C()l’YRIGIIT © 2016
`
`0R1G1NéLi!RT1CLE§
`
`9
`
`I4
`
`37
`
`47
`
`55
`
`62
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`70
`
`79
`
`89
`
`Anti-Aging Effects of Probiotics
`Divya Sharma BS, Mary—Margaret Kober MD, and Whitney P. Bowe MD
`
`Fractional Ablative Laser Followed byTransdermal Acoustic Pressure Wave
`Device to Enhance the Drug Delivery of Aminolevulinic Acid: In Vivo Fluorescence
`Microscopy Study
`Jill 5‘. Waibel MD, Ashley Rudnick, Carlos Nousari MD, and Dhaval G. Bhanusali MD
`
`Natural Cosmeceutical Ingredients for Hyperpigmentation
`Noelani Gonzalez MD and Maritza Perez MD
`
`Comparative Study of Professional vs Mass MarketTopical Products forTreatment
`of Facial Photodamage
`Hilary Reich MD, lrmina Wallander BA, Lacie Schulte MS BA, Molly Goodier BS,
`and Brian Zelickson MD
`
`A Firming Neck Cream Containing N-Acetyl Glucosamine Significantly Improves
`Signs of Aging on the Challenging Neck and Décolletage
`Joel Sch/essinger MD, Barbara Green RPh MS, Brenda L. Edison BA, Lynn Murphy MA,
`and Yamini Sabherwal PhD
`
`I
`
`Effects of Subdermal Monopolar RF Energy on Abdominoplasty Flaps
`John Ferguson MD
`
`Assessing Improvement of Facial Appearance and Quality of Life after Minimally-
`Invasive Cosmetic Dermatology Procedures Using the FACE-Q Scales
`Brian P Hibler BS, Jonathan Schwitzer MD, and Anthony M. Rossi MD
`
`Safety and Effectiveness of Hyaluronic Acid lnjectable Gel in Correcting Moderate
`Nasolabial Folds in Chinese Subjects
`Yan Wu MD PhD, Jinhua Xu PhD, Yi Jia MD MSc PhD, and Diane K. Murphy MBA
`
`Evolution of Acne Assessments and Impact on Acne Medications: An Evolving,
`Imperfect Paradigm
`Linda Stein Gold MD, Jerry Tan MD, and Leon Kircik MD
`
`Evaluation of the Appearance of Nail Polish Following Dai|yTreatment of ExVivo
`Human Fingernails With Topical Solutions ofTavaborole or Efinaconazole
`Tracey C. Vlahovic DPM, Dina Coronado BS, Sanjay Chanda PhD, Tejal Merchant MPharm,
`and Lee 7." Zane MD
`
`Th is material wastes-pied
`at the N LM and may be
`5ul:rjes:t US Co-pyright Laws
`
`CFAD v. Anacor, |PR20‘|5-01776
`ANACOR EX. 2159 - 2/‘IO
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 2/10
`
`

`
`JANUARY 2016
`
`Issuu I COPYRIGIIT © 2016
`
`VOLUME I5 -
`
`JOURNAL 011 DRUGS IN DERMATOLOGY
`
`QIEIGINAL @I¥T1CLE3..(C.Q.N.TDs)
`
`97
`
`iPLEDGE Weaknesses: Is It Time to Address the Flaws?
`
`Amanda A. Cyrulnik MD, Aron J. Gewirtzman MD, Karin Blecher Paz MD, Jaimie B. G/ick MD,
`Anika K. Anam MD, DanielA. Carrasco MD, Alan R. Shalita MD, and Steven R. Cohen MD MPH
`
`104
`
`Luliconazole Retention in Stratum Corneum and Prevention of Fungal Infection in
`a Guinea Pig Tinea Pedis Model
`Hiroyasu Koga PhD, Yasuko Nanjoh, Tetsuo Toga PhD, Radhakrishnan Pi/lai PhD, William Jo PhD,
`
`and RyojiTsuboi PhD
`
`CASE UREBQRTS
`
`111
`
`A Combination Approach to Perioral Rejuvenation
`Rebecca 8. Danhof MD MPH and Joel L. Cohen MD
`
`114 Horrendous,Treatment-resistant Pediatric Atopic Dermatitis Solved With a Change
`in Vehicle
`
`Tejaswi Mudigonda BS, William Kaufman MD, and Steven R. Feldman MD PhD
`
`BESIDUENUT 15}0U.N12S_.
`
`117 The University of Pittsburgh Residency Program in Dermatology:
`In Memoriam, Dr. Lisa Grandinetti
`Kristen Lo Sicco MD
`
`FEATURED CQNTENT
`
`119 ClinicalTrial Review
`
`This mate-rialw‘as—w-pielj
`m“eNL*~*a”dm~W
`Su bject US {lo-pzyright Laws
`
`V. AnaCCr,
`ANACOR EX. 2159 — 3/10
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 3/10
`
`

`
`JANUARY 2016
`COI’YRlGlI'I‘
`2016
`
`
`
`
`]oUitNAL oi= DRUGS IN DL=iziviA't'oLoGY
`
`VOLUME 15
`
`-
`
`Issue 1
`
`PUBLISIITERS
`Shelley N. F;i1iiici'
`Lawrence E. Robins
`
`EXECU'['IVI£ Enrroit
`Karin Bceliler
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`ASSIS'I'AN'I' EDITOR
`Katlilccii Leary RN
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`ASSOCIATI.-' PUBLISHER
`
`Nick Gillespie
`
`Sc1uNTti=1c PUBLICATIONS LIAISON
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`DESIGN
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`Journal ofDrugs in Dermatal0UV(JDD) (ISSN 1545-9616) is published monthly
`for$300 per year (US subscriptions)/$350 per year (International subscriptions)
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`'17 2016 Journal of Drugs in Dermatology
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`Inflammatory Acne Vulgarisz
`Current Concepts in
`Pathogenesis and Nlanagernent
`
`Leon I-I. Kircik MD ziiidjoslitia A. Zeicliner MD
`
`JouiLNAL OI‘ iiitutis iN DI.|(l\1/\I()l.()UY
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`ft?’
`
`_
`“
`
`This material was copied
`at the NLM and may be
`Su btjen: US CCrl}y‘l'l§i'1‘i‘.‘ Laws
`
`CFAD v. Anacor, |PR20‘l5-01776
`ANACOR EX. 2159 - 4/‘IO
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 4/10
`
`

`
`r 1'5 mteva my 3e 3’L\tet.te€i 3y L‘t\3y*'g; ‘it aw jrt e :7 u 5 Code)
`
`JANUARY 3016
`
`COPYRIGIIT © 2016
`
`89
`
`
`
`
`VOLUME I5 -
`Issue 1
`JOURNAL ()l‘ DRUGS IN i)l£l{MA'I'OL()(3Y
`
`
`
`Evaluation of the Appearance of Nail Polish Following Daily
`Treatment of EX Vivo Human Fingernails With Topical
`Solutions of Tavaborole or Efinaconazole
`
`Tracey C.VlahoVic DPM,“ Dina Coronado BS," Sanjay Chanda PhD,"Tejal Merchant Ml’h;u'n1,“
`and Lee T. Zane MD“
`
`"Temple University School ofPodi;1tric Medicine, Piiiiadeipiiia, PA
`"Anacor l’11ar111aceuticais, lnc., Palo Alto, CA
`
`
`W3 '. ~P3A'G:T@ ..
`
`introduction: Patients with onychomycosis may mask infected nails with polish. Tavaborole topical solution, 5% is a boron-based
`small-molecule pharmaceutical approved for the treatment of toenail onychomycosis caused by Trichophyton rubrum and Tr/chophyton
`mentagrophytes; efinaconazole topical solution, 10% is approved for the same indication. Nail polish appearance after application of
`tavaborole (dropper) or efinaconazole (brush); respective applicator appearance; presence of color transfer from respective applicators;
`and color transfer to remaining solutions after dosing of polished nails were evaluated.
`Methods: Twelve ex vivo human cadaver fingernails were cleaned, polished with two coats of l_'Oréal“~” Nail Color, Devil Wears Red
`
`4
`
`#420, and mounted on floral foam. Nails were treated with tavaborole or efinaconazole solutions once daily for 7 days. Dropper and
`brush applicators were applied to white watercolor paper immediately after dosing to evaluate color transfer from polished nails. On
`day 7, remaining solutions were transferred to clear glass vials to evaluate color transfer from applicators to solutions. Nails, applicators,
`and papers were photographed daily following application; remaining solutions were photographed after 7 days of dosing.
`Results: Tavaborole-treated polished nails showed no polish discoloration, and tavaborole applicators did not change in appearance
`during treatment. No color transfer from polished nails was evident to applicator, paper, or remaining solution. Eflnaconazole-treated
`polished nails showed substantial polish changes after the first day of treatment, with polish appearance and discoloration progres-
`sively worsening over 7 days of treatment. Color transfer from nails was evident to applicator, paper, and remaining solution.
`Conclusions: Daily dropper application of tavaborole to ex vivo polished nails did not alter polish appearance. Brush application of efi—
`naconazole produced visible changes in polish appearance and color transfer to applicators, paper, and remaining solution.Tavaborole
`topical solution, 5% may not alter nail polish appearance; the impact of nail polish on tavaborole clinical efficacy has not been evaluated.
`
`i
`
`_
`i
`
`i
`
`J Drugs Dermatol. 20i6;15(i):89-94.
`
`E
`
`i
`
`
`
`l1NTR‘oDUGTroN§
`
`
`nychomycosis is a common fungal infection of the nail
`
`E unitthatcan causesubungual hyperkeratosis,thicken-
`
`ing and discoloration of the nail, and onycholysis.”
`The unsightly appearance of the diseased nail can cause so-
`cial embarrassment and negatively impact patient self-image.“
`Even with successful treatment, complete regrowth of healthy
`toenails can take up to 18 months.‘ During this time, patients
`may choose to mask discolored infected nails with polish; thus,
`the compatibility of nail polish with topical antifungal treat-
`ments is an important consideration for many patients with
`onychomycosis.
`
`Treatment of onychomycosis is challenging due to the inability
`of some drugs to effectively penetrate the nail and reach fungal
`pathogens located beneath the nail plate.5 Until recently, the
`only US Food and Drug Administration (FDA)-approved topi-
`cal treatment for onychomycosis was ciclopirox nail lacquer,
`8%.“ However,
`in 2014, the FDA approved two new topical
`
`antifungals for the treatment of onychomycosis of the toenails
`caused by Trichophyton rubrum or Trichophyton mentagro—
`phytes, including Kerydin'” (tavaborole topical solution, 5%;
`Anacor Pharmaceuticals, lnc., Palo Alto, CA), a boron-based
`small-molecule pharmaceutical,7 and Jublia” (efinaconazole
`topical solution, 10%; Valeant Pharmaceuticals, LLC, Bridge-
`water, NJ)!’
`
`Findings from in vitro studies have established the effective
`penetration of tavaborole through full-thickness human nail
`plates to the nail bed, where the fungal infection resides.°“°
`importantly, tavaborole has been shown to retain its phar-
`macologic antifungal activity in the presence of keratin after
`permeating the nail plate. Similarly, nail—penetration studies in
`patients with toenail onychomycosis have shown the ability of
`efinaconazole to penetrate the subungual space between the
`nail plate and nail bed.“ in addition, in vitro permeation studies
`have been conducted.Tavaborole was shown to penetrate up
`
`This material wasmpiead
`at the N LM a rid may he
`L‘-.u'i:»ject U&Cd~py‘rig.ht Laws
`
`CFAD v. Anacor, |PR20‘l5-01776
`ANACOR EX. 2159 - 5/‘IO
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 5/10
`
`

`
` JOURNAL or= DRUGS IN DERMATOL()GY
`
`
`T.C.V1ahovic, D. Coronado, S. Chanda, et al
`
`ISSUE 1
`
`JANUARY 2016 - VOLUME '15
`
`-
`
`FIGURE 1. Dosing schematic fortavaborole topical solution, 5% and efinaconazole topical solution, 10% fortreating polished nails.
`
`Treatment Group: Efinaconazole-Treated Nails
`
`
`
`
`Efinaconazole 1
`
`
`
`Efinaconazole 2
`
`
`
`
`
`
`
`Efinaconazole 3
`
`
`
`Efinaconazole 4
`
`
`
`Treatment Group: Tavaborole-Treated Nails
`
`Tavaborole 1
`
`Tavaborole 2
`
`Tavaborole 3
`
`Tavaborole 4
`
`Treatment Group: Control
`
`
`
`
`
`
`
`Dose on paper
`
`to 4 layers of nail polish." Permeation of efinaconazole through
`unpolished and polished nails was reported by Ziechner et al”;
`however, transfer of polish color to the efinaconazole brush
`applicator and progressive tackiness of the polish finish with
`repeated application were also observed.'3The impact of nail
`polish on the clinical efficacy of both tavaborole and efinacon-
`azole has not been evaluated.
`
`The objective of the current study was to further characterize
`and compare the effects of tavaborole and efinaconazole ap-
`plication on polished nails by evaluating the appearance of
`ex vivo polished nails after 7 days of daily dosing with the
`specific applicators used for tavaborole topical solution, 5%
`(dropper applicator) and efinaconazole topical solution, 10%
`(brush applicator). Applicator appearance and color transfer
`from polished nails to applicators and color transfer from
`applicators to paper after daily applications, as well as color
`transfer from applicators to treatment solutions after 7 days of
`dosing were also evaluated.
`
`(METHODS?
`
`Two treatment groups were evaluated, each containing 6 ran-
`domly selected, non—diseased human fingernails (1 or 2 nails per
`donor) from 4 human cadaver donors (SciKon Innovations, |nc.,
`ResearchTriangle Park, NC). Nails were cleaned; characterized for
`width, length, thickness, and weight; polished with 2 coats of a
`commonly available brand of nail polish (L’Oréal® Devil Wears
`Red #420; l.’Oréal Paris, Montréal, Québec, Canada); and mounted
`(Kiss Maximum Speed Nail Glue, Lot #GL30309, New York, NY)
`on wet floral foam (Floracraft MPFF1S/18, Pomona, CA) to main-
`
`tain nail position and hydration. Overall, nails were similar with
`regard to nail length (range, 10.02-12.06 mm), nail width (range,
`53.95-14.39 mm), and nail thickness (range, 0.31-0.85 mm).
`
`Nails were randomly assigned to treatment with tavaborole topical
`solution, 5% applied with dropper once daily for 7 days or efina-
`conazole topical solution, 10% applied with brush once daily for
`7 days, as per their respective patient instructions (Figure 1). A
`
`This mate rial was copied
`atthee NLM and may be
`Subject.‘ US~{io~pwy‘right Laws
`
`CFAD V. Anacor, |PR2015-01776
`ANACOR EX. 2159 - 6/10
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 6/10
`
`

`
`JOURNAL o1= DRUGS IN DERMATOLOGY
`JANUARY 2016 - VOLUME 15 -
`ISSUE 1
`
`T.C.VlahoVic, D. Coroitado, S. Chanda, et al
`
`91
`
`total of 2 bottles each of tavaborole topical solution, 5% or efina-
`conazole topical solution, 10% were used to apply solution with
`respective applicators to a single nail. Similarly, a total of 2 bottles
`each of tavaborole topical solution, 5% or efinaconazole topical so-
`lution, 10% were used to apply solution with respective applicators
`to 2 consecutive nails. A total of 6 nails each (12 total nails) were
`treated with tavaborole topical solution, 5% or efinaconazole topi-
`cal solution, 10%.
`
`A subset of applicators used to apply solution to the polished
`nails were also used to apply solution to a sheet of white wa-
`tercolor paper each day immediately after closing the nails to
`assess any color transfer from the respective applicators to
`the paper (Figure 1). Specifically, 1 of 2 bottles each of tava-
`borole topical solution, 5% or efinaconazole topical solution,
`10% used to apply solution with respective applicators to a sin-
`gle nail, or used to apply solution with respective applicators
`to 2 consecutive nails, were used to apply solution to white
`watercolor paper. The control group included one bottle each
`
`of tavaborole topical solution, 5% and efinaconazole topical
`solution, 10% that were only used to apply solution to the wa-
`tercolor paper each day, but were not used to apply solution
`to polished nails.
`
`To document changes in appearance, the test nails, used ap-
`plicators, and watercolor papers were photographed (Nikon
`D90 digital SLR camera with Stereotactic Nail Device, Nikkor
`60 mm lens, Melville, NY; Canfield TwinFlash, Fairfield, NJ)
`daily following the treatment applications. At the end of the
`study, each bottle of solution was opened, poured into a clear
`glass vial, and compared with the respective control bottle so-
`lution to evaluate color differences.These solutions were also
`
`photographed to evaluate any color transfer from the appli-
`cators to the remaining solutions. Photographs were labeled
`with treatment group number, applicator number, study day,
`and date.
`
`"Treatment of onychomycosis is
`challenging due to the inability of
`some drugs to effectively penetrate the
`nail and reach fungal pathogens located
`beneath the nail plate."
`
`’aREst~JLTsfi
`
`Following daily application, polished nails treated with tava-
`borole topical solution, 5% showed no signs of discoloration
`during the 7-day treatment period, and nails appeared to dry
`within minutes of application. Alternatively, polished nails
`treated with efinaconazole topical solution, 10% had noticeably
`changed in appearance and were discolored starting from
`
`the initial application. Appearance of the nails progressively
`worsened with repeated treatment application through day 7
`as evidenced by photographs (Figure 2). Nails appeared tacky
`upon contact with the brush applicator following the first appli-
`cation and remained tacky for the duration of the study.
`
`Dropper applicators used for tavaborole topical solution, 5%
`did not change in appearance during the treatment period. In
`contrast, color transfer was observed in the brush applicators
`
`used for efinaconazole topical solution, 10% after the first appli-
`cation; the white applicator became pink/red from the transfer
`of nail polish from the polished nail to the applicator.This color
`transfer became increasingly more evident upon repeated ap-
`plication, and was most apparent on the brush applicator on
`day 4 of dosing (Figure 3).
`
`No color transfer was evident from the polished nails treated
`with tavaborole topical solution, 5% to the white watercolor
`paper (Figure 4). Similarly,
`the remaining treatment solu-
`tion was not discolored at the end of the treatment period
`on day 7 (Figure 5). However, color transfer from the polished
`nails treated with efinaconazole topical solution, 10% was
`evident on the white watercolor paper following treatment
`of either a single nail or 2 consecutive nails throughout the
`treatment period. Furthermore, the efinaconazole treatment so-
`
`lution transferred from the original bottle at the end of 7 days
`exhibited a pink hue when compared with the control solution
`that did not come into contact with polished nails.
`
`EDIScUss1oNii4tND}'coNcLUsIoN§
`
`
`
`Because of the social embarrassment associated with onycho-
`mycosis and the extended duration of treatment time required
`
`to achieve improvements in nail appearance and regrowth of
`healthy nails, patients with onychomycosis may choose to mask
`nail abnormalities with nail po|ish.Tavaborole has been previ-
`ously shown in an in vitro study to effectively penetrate the
`nail plate in the presence of up to 4 layers of brand nail polish,
`suggesting that the presence of nail polish does not inhibit the
`ability of tavaborole to reach the fungal infection beneath the
`nail bed."The objectives of the current in vitro study were to
`evaluate nail polish appearance, respective applicator appear-
`ance, and the resulting nail polish color transfer to respective
`applicators and remaining solutions following application of
`tavaborole topical solution, 5% or efinaconazole topical solu-
`tion, 10% to ex vivo polished nails. Nails were treated once
`daily for 7 days using the respective applicators and following
`the application procedures described in the patient instructions
`for each product.
`
`Findings of the current study demonstrated that nail polish
`remained intact after once-daily application of tavaborole
`topical solution, 5%, to ex vivo polished nails for 7 days. No
`color transfer to the tavaborole dropper, watercolor paper, or
`
`This material was copied
`at the NLM and may be
`Su l.}jzE'ET. U5 {it:rpsy‘rigl1t.‘ Laws
`
`CFAD v. Anacor, |PR20‘l5-01776
`ANACOR EX. 2159 - 7/10
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 7/10
`
`

`
`92
`
`JOURNAL on DRUGS IN DERMA’I"()LOGY
`JANUARY 2016 - VOLUME 15 -
`ISSUE 1
`
`T.C.Vlal1ovic, D. Coronado, S. Chanda, et 31
`
`FIGURE 2. Appearance of polished nails aftertreatment with tavaborole topical solution, 5% and efinaconazole topical solution, 10%.
`
`Tavaborole Topical Solution, 5%
`
`Efinaconazole Topical Solution, 10%
`
`Day 0
`
`(Pre-dose)
`
`Day 1
`
`(First dose)
`
`Tavaborole
`dropper
`
`Efinaconazole
`brush
`applicator
`
`Tavaborole
`dropper
`
`Efinaconazole
`brush
`applicator
`
`Tavaborole
`dropper
`
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`brush
`applicator
`
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`
`Efinaconazole
`brush
`applicator
`
`This mate rial was copied
`atthee NLM and may DE
`Su'l:;je{t.‘ US~{ia~pwy‘right Laws
`
`CFAD V. Anacor, |PR2015-01776
`ANACOR EX. 2159 - 8/10
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 8/10
`
`

`
`
`T.C.Vlahovic, D. Coronado, S. Cl1a11d;1, et :11
`JOURNAL OF DRUGS IN DERMATOLOGY
`JANUARY 2016 - VOLUME 15 -
`ISSUE 1
`
`
`93
`
`FIGURE 4. Colortransferfrom solution applicators to white watercolor paper.
`
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`Th is material was cu-pied
`at the NLM and may be
`SL2 bjett US CCrl}y‘l'l§l'l‘l‘.‘ Laws
`
`CFAD v. Anacor, |PR20‘|5-01776
`ANACOR EX. 2159 - 9/‘IO
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 9/10
`
`

`
` T.C.V1ahovic, D. Coronado, S. Chzulda, et al
`
`JOURNAL OF DRUGS IN DERMATOLOGY
`JANUARY 2016 ° VOLUME 15 -
`ISSUE 1
`
`94
`
`FIGURE 5. Appearance of drug solutions at day 7 (end of study).
`
`Tavaborole Topical Solution, 5%
`
`Efinaconazole Topical
`
`Solution, 10%
`
`
`
`'A'cKNo,W.I:ED’GMENTs§
`lnc.,
`This study was sponsored by Anacor Pharmaceuticals,
`Palo Alto, CA. Writing and editorial assistance was provided
`to the authors by Callie Grimes PhD and Chad Williamson MS
`of Echelon Brand Communications, Parsippany, NJ, and was
`funded by Anacor Pharmaceuticals, lnc., Palo Alto, CA. Diane
`Nelson RN MPH ofAnacor Pharmaceuticals, Inc. provided criti-
`cal review and revision to the manuscript. The authors were
`fully responsible for the content, editorial decisions, and opin-
`ions expressed in the current article. No author received an
`honorarium related to the development of this manuscript.
`
`
`
`:iDIs'GL'o’sUREsfi
`Tracey C. Vlahovic has received honoraria as a speaker for Ana-
`cor Pharmaceuticals, Inc. and as an advisory board member
`for Merz Pharma and Valeant Pharmaceuticals. Dina Coronado,
`
`Sanjay Chanda,Teja| Merchant, and LeeT. Zane are employees
`of Anacor Pharmaceuticals, Inc.
`
`
`1.
`
`2.
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`3.
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`4.
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`5.
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`6.
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`7.
`8.
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`9.
`
`.5KEFER‘-RENGES
`
`Scher RK,Taval<kol A, Sigurgeirsson B, et al. Onychomycosis: diagnosis and
`definition of cure. JAm Acad Dermazo/. 2007;56:939-944.
`Elewski BE, Rich P,Tosti A, et al. Onchomycosis: an overview. J Drugs Der-
`mato/. 2013;12:596-103.
`Elewski BE.The effect of toenail onychomycosis on patient quality of life. Int
`J Dermatol. 1997;36:754-756.
`Thomas J, Jacobson GA, Narkowicz CK, Peterson GM, Burnet H, Sharpe C.
`Toenail onychomycosis: an important global disease burden. J Clin Pharm
`Ther. 2010;35:497-519.
`Alley MR, Baker SJ, Beutner KR, Plattner J. Recent progress on the topi-
`cal therapy of onychomycosis. Expert Opin /nvestig Drugs. 2007;16:157-167.
`Penlac [package insert]. Bridgewater, NJ: Dermik Laboratories, a division of
`sanofi~aventis US. LLC; 2006.
`Kerydin [package insert]. Palo Alto, CA: Anacor Pharmaceuticals, |nc.; 2014.
`Jublia [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North
`America, LLC; 2015.
`Hui X, Baker SJ, Wester RC, et al. in Vitro penetration of a novel oxaborole
`antifungal (AN2690l into the human nail plate. J Pharm Sci. 2007;96:2622-
`2631.
`in vitro nail penetration and an-
`Coronado D. MerchantT, Chanda 8, Zane L.
`tifungal activity of tavaborole, a novel, boron-based pharmaceutical. J Drugs
`Dermazol. 2015;14:609-614.
`Elewski BE, Pollak RA, Pillai R, Olin JT. Access of efinaconazole topical solu-
`tion, 10%, to the infection site by spreading through the subungual space. J
`Drugs Dermaro/. 2014:13:1394-1398.
`VlahovicT, MerchantT, Chanda S, Zane L, Coronado D. In vitro nail penetra-
`tion of tavaborole topical solution, 5% through nail polish on ex vivo human
`fingernails. J Drugs Dermatol. 2015;14:675-678.
`Zeichner JA, Stein GL, Korotzer A. Penetration of (”C)~efinaconazole topical
`solution, 10%, does not appear to be influenced by nail polish. J Clin Aesthet
`Dermato/. 2014:7234-36.
`
`10.
`
`11.
`
`12.
`
`13.
`
`AUTHOR CORRESPONDENCE
`
`Tracey C. Vlahovic DPM
`E-mail: ............................................................ .. traceyv@temple.edu
`
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`solution was evident during the course of the study. In con-
`trast, once-daily application of efinaconazole topical solution,
`10% resulted in substantial alterations to the polish includ-
`ing discoloration, polish tackiness, and polish transfer from
`nails to brush applicators and from brush applicators to white
`watercolor paper as early as study day 1.The treated nails ap-
`peared to remain tacky throughout the remainder of the study.
`At the end of the study, the efinaconazole solution remaining
`in the bottle had a pink hue when compared with the control
`solution. In addition, color transfer to the applicator appeared
`lighter on day 7 compared with day 4, which was likely the
`result of nail polish color transfer from the brush applicator to
`the efinaconazole remaining solution in the bottle.
`
`These findings are consistent with those of a previous study
`that examined the compatibility of efinaconazole topical so-
`lution, 10% and nail polish using ex vivo human fingernails;
`polish transfer to the efinaconazole brush applicator was ob-
`served following the first application, and surface tackiness of
`the nail polish caused by the efinaconazole solution worsened
`with repeated application.”
`
`Limitations of the current study include the small sample size, the
`ex vivo nature of the study design, the use of non-diseased finger-
`nails, and the type of nail polish used. It is important to note that
`clinical efficacy oftavaborole topical solution, 5% or efinaconazole
`topical solution, 10% with concomitant use of nail polish has not
`been evaluated in patients with toenail onychomycosis.“
`
`Results of the current study demonstrate that daily application
`with tavaborole topical solution, 5% to ex vivo polished nails did
`not alter nail polish appearance. Application of efinaconazole
`topical solution, 10% substantially altered polish appearance
`and transferred polish from nails to applicators, from applica-
`tors to paper, and from applicators to the remaining solution in
`the bottle. The aesthetic compatibility of tavaborole with pol-
`ished nails may allow patients the option of using nail polish
`when undergoing tavaborole treatment.
`
`This material was copied
`at the NLM and may be
`Su.l:ijes:t.‘ U5 {lo-p-yrigrht Laws
`
`CFAD V. Anacor, |PR2015-01776
`ANACOR EX. 2159 - 10/10
`
`CFAD v. Anacor, IPR2015-01776
`ANACOR EX. 2159 - 10/10