Efficacy and safety of tavaborole topical solution,
`5%, a novel boron-based antifungal agent,
`for the treatment of toenail onychomycosis:
`Results from 2 randomized phase-III studies
`
`Boni E. Elewski, MD,a Raza Aly, PhD,b Sheryl L. Baldwin, RN,c Remigio F. Gonzalez Soto, MD,d
`Phoebe Rich, MD,e Max Weisfeld, DPM,f Hector Wiltz, MD, CPI,g
`Lee T. Zane, MD,d and Richard Pollak, DPM, MSh
`Birmingham, Alabama; San Francisco and Palo Alto, California; Monterrey, Mexico;
`Portland, Oregon; Baltimore, Maryland; Miami, Florida; and San Antonio, Texas
`
`Background: Onychomycosis, a fungal nail infection, can impact quality of life.
`
`Objective: We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of
`toenail onychomycosis.
`
`Methods: In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target
`great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point
`was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52.
`Secondary end points included completely or almost clear nail, negative mycology, completely or almost
`clear nail plus negative mycology, and safety.
`
`Results: Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs
`0.5% and 1.5%) significantly favored tavaborole versus vehicle (P # .001). Completely or almost clear nail
`rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P \ .001). Rates of
`completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly
`greater for tavaborole versus vehicle (P \ .001). Application-site reactions with tavaborole included
`exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%).
`
`Limitations: Duration of follow-up is a limitation.
`
`From the Department of Dermatology, University of Alabama at
`Birminghama; Department of Dermatology, University of
`California, San Franciscob; Anacor Pharmaceuticals,
`Inc, Palo
`Altoc; Centro de Dermatologia de Monterreyd; Oregon Health
`and Science Universitye; Hamilton Foot Care, Baltimoref; FXM
`Research Corp, Miamig; and Endeavor Clinical Trials, San
`Antonio.h
`Writing and editorial assistance was provided by Callie Grimes of
`Peloton Advantage, LLC, Parsippany, NJ, and was supported by
`Anacor Pharmaceuticals,
`Inc. Diane Nelson of Anacor
`Pharmaceuticals, Inc, provided critical review and revision of
`the manuscript.
`Disclosure: Ms Baldwin and Dr Zane are employees of Anacor
`Pharmaceuticals,
`Inc. Dr Elewski has received honoraria and
`grants while serving as a consultant and investigator with the
`following companies: Anacor Pharmaceuticals,
`Inc; Valeant
`Pharmaceuticals International Inc, Bridgewater, NJ; and Meiji
`Seika Pharma Co, Ltd, Tokyo, Japan. Dr Aly was consultant and
`investigator for Anacor Pharmaceuticals, Inc. Dr Gonzalez Soto
`was an investigator
`for
`the following companies: Anacor
`Pharmaceuticals,
`Inc; Pfizer, New York, NY; and Eli Lilly,
`Indianapolis,
`IN. Dr Rich was the principal
`investigator for
`onychomycosis studies with the following companies: Anacor
`
`62
`
`Inc; Topica Pharmaceuticals, Los Altos, CA;
`Pharmaceuticals,
`Valeant Pharmaceuticals
`International
`Inc;
`and Viamet
`Pharmaceuticals Inc, Durham, NC. Dr Pollak has received grants
`and honoraria while serving as advisory board member,
`investigator, and speaker for the following companies: Anacor
`Pharmaceuticals, Inc; Valeant Pharmaceuticals International Inc;
`and Topica Pharmaceuticals. Drs Weisfeld and Wiltz were
`principal
`investigators for Anacor Pharmaceuticals,
`Inc. The
`authors were fully responsible for
`the content, editorial
`decisions, and opinions expressed in the current article. No
`author received an honorarium related to the development of
`this manuscript.
`Accepted for publication April 6, 2015.
`Reprint requests: Boni E. Elewski, MD, Department of Dermatology,
`University of Alabama at Birmingham, EFH 414, 1530 3rd Ave S,
`Birmingham, AL 35294-0009. E-mail: beelewski@aol.com.
`Published online May 5, 2015.
`0190-9622
`Ó 2015 by the American Academy of Dermatology, Inc. Published
`by Elsevier, Inc. This is an open access article under the CC
`BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
`nd/4.0/).
`http://dx.doi.org/10.1016/j.jaad.2015.04.010
`
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`J AM ACAD DERMATOL
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`Elewski et al 63
`
`Conclusion: Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomy-
`cosis. ( J Am Acad Dermatol 2015;73:62-9.)
`
`Key words: antifungal agents; arthrodermataceae; nails; onychomycosis; randomized controlled trial;
`tavaborole.
`
`CAPSULE SUMMARY
`
`d Tavaborole topical solution, 5% is
`approved for treatment of toenail
`onychomycosis.
`
`Tavaborole topical solu-
`tion, 5% (Anacor Pharmaceu-
`ticals, Inc, Palo Alto, CA) is a
`novel, boron-based pharma-
`ceutical approved by the Food
`and Drug
`Administration
`(FDA)
`in July
`2014
`for
`the
`treatment
`of
`toenail
`onychomycosis
`caused by
`Trichophyton rubrum and T
`mentagrophytes.1 Tavaborole
`represents a new class of phar-
`maceutical antifungal agents
`with a novel chemical structure
`and mechanism of action
`(Fig 1).2-5 Tavaborole targets
`fungal
`cytoplasmic
`leucyl-
`transfer ribonucleic acid (tRNA) synthetase, a member
`of a family of aminoacyl-tRNA synthetase enzymes
`essential for protein synthesis.5 These enzymes maintain
`and translate genetic code within DNA, and possess a
`proofreading mechanism that corrects enzymatic
`mistakes that occur on a separate, active editing site.
`Tavaborole binds to the editing site via its boron atom to
`trap leucyl
`tRNA, preventing its catalytic turnover
`and inhibiting protein synthesis. Tavaborole demon-
`strates broad-spectrum antifungal activity and more
`than 1000-fold greater
`selectivity for
`the fungal
`leucyl-tRNA synthase than the mammalian leucyl-tRNA
`synthetase6; T rubrumand T mentagrophytes isolates
`collected from clinical
`trial patients have not
`demonstrated resistance after repeated exposure to
`tavaborole.1
`The low molecular weight of tavaborole allows a
`high amount of penetration through full-thickness
`human nail plates.7 Ex vivo permeation studies have
`demonstrated
`tavaborole penetration
`through
`multiple layers of nail polish (data on file, Anacor
`Pharmaceuticals, Inc; TER-002-14, ANA-005, 2013).
`Phase-I
`trials showed favorable safety and low
`systemic
`exposure
`in patients with
`toenail
`onychomycosis,8
`and phase-II
`trials provided
`evidence of
`improved clear nail growth and
`negative fungal cultures.9 The objective of the 2
`phase-III trials described herein was to evaluate
`the efficacy and safety of
`tavaborole versus
`vehicle in adults with distal subungual
`toenail
`onychomycosis.
`
`METHODS
`Study treatment and
`patients
`inclu-
`Study treatments
`ded tavaborole and vehicle,
`which were applied topically
`to the affected nails once
`daily for 48 weeks by the
`patient. Patients were in-
`structed to apply a sufficient
`amount of study treatment
`on,
`under,
`and
`around
`the infected target great
`toenail (TGT) and infected
`nontarget
`toenails with a
`thin, even layer.
`Patients 18 years of age or
`older with distal subungual toenail onychomycosis
`involving 20% to 60% of at least 1 TGT were eligible if
`they had a positive potassium hydroxide (KOH) wet
`mount and positive culture for dermatophytes,
`greater than or equal to 3-mm clear nail measured
`from the proximal nail fold to the most proximal
`visible mycotic border, and distal TGT thickness
`3 mm or
`less. Patients were excluded if
`they
`had proximal
`subungual or
`superficial white
`onychomycosis, severe disease, dermatophytoma,
`exclusively lateral disease, yellow/brown spikes,
`coinfection with nondermatophyte fungi, anatomic
`abnormalities of the toes or toenails, active tinea
`pedis (involving the sides or back of
`the foot,
`interdigital, or plantar) requiring treatment, history
`of chronic moccasin-type tinea pedis (involving the
`sides or back of the foot), history of other significant
`chronic fungal disease, psoriasis,
`lichen planus,
`known immunodeficiency, significant peripheral
`vascular disease, known structural heart disease, or
`uncontrolled diabetes (hemoglobin A1C $8%).
`Patients who used topical antifungals on the toenails
`within 4 weeks or systemic antifungals within
`24 weeks were also excluded. Recent use of other
`topical agents on the toe or toenails, systemic
`corticosteroids, or immunomodulatory agents was
`not permitted.
`
`d Tavaborole was significantly more
`effective than vehicle in treating toenail
`onychomycosis in 2 phase-III trials;
`incidence of treatment-related
`application-site reactions was low.
`
`d The favorable benefit-risk profile makes
`tavaborole a reasonable therapeutic
`option for toenail onychomycosis.
`
`Study design
`Two phase-III, multicenter, randomized, double-
`blind, vehicle-controlled, parallel-group trials of
`
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`64 Elewski et al
`
`J AM ACAD DERMATOL
`JULY 2015
`
`Abbreviations used:
`
`AE:
`FDA:
`KOH:
`TEAE:
`TGT:
`tRNA:
`
`adverse event
`Food and Drug Administration
`potassium hydroxide
`treatment-emergent adverse event
`target great toenail
`transfer ribonucleic acid
`
`identical design were conducted: 1 at 27 sites in the
`United States and Mexico from December 2010 to
`November 2012 (study 1; NCT01270971) and the
`other at 32 sites in the United States and Canada from
`February
`2011
`to
`January
`2013
`(study
`2;
`NCT01302119). Both studies were conducted in
`accordance with ethical principles originating in
`the Declaration of Helsinki and in compliance with
`the principles of Good Clinical Practice and all
`applicable regulatory requirements. The study
`protocol was approved by an institutional review
`board/independent ethics committee at each site,
`and all patients provided written informed consent.
`Patients were screened 4 to 10 weeks before
`randomization. Eligible patients were randomized
`2:1 to receive tavaborole or vehicle, and applied
`study treatment to the TGT and all other affected
`toenails once daily for 48 weeks. Nail debridement
`was not permitted.
`Disease involvement was assessed at screening,
`baseline (day 1), week 2, week 6, and every 6 weeks
`thereafter. At
`these visits, nail
`trimming of
`the
`TGT was limited to within 1 mm distal
`to the
`hyponychium or distal groove if needed. Patients
`were encouraged not to trim the TGT. All other
`toenails were also evaluated for
`the presence
`of onycholysis and subungual hyperkeratosis.
`Subungual samples were obtained from the TGT at
`screening and every 12 weeks during treatment and
`sent to a central mycology laboratory for KOH wet
`mount examination with calcofluor white stain and
`fungal culture to identify pathogenic fungi including
`dermatophyte
`species. After
`study
`treatment
`was completed at week 48,
`follow-up efficacy
`assessments were made at week 52.
`
`Efficacy
`The primary efficacy end point was complete cure
`of the TGT defined as completely clear nail and
`negative mycology at week 52. Secondary end points
`included completely or almost clear nail of the TGT,
`negative mycology of the TGT, and completely or
`almost clear nail plus negative mycology, each
`determined at week 52. Completely clear nail was
`defined as no clinical evidence of onychomycosis
`based on a normal toenail plate, no onycholysis, and
`
`Fig 1. Tavaborole chemical structure. Tavaborole is a
`novel, boron-based pharmaceutical approved for the
`treatment of toenail onychomycosis caused by Trichophy-
`ton rubrum and T mentagrophytes.1 Tavaborole inhibits
`leucyl-tRNA-synthetase, resulting in inhibition of fungal
`protein synthesis and termination of fungal cell growth.5
`
`no subungual hyperkeratosis. Almost clear nail was
`defined as no more than minimal evidence of
`onychomycosis based on a toenail plate that was
`dystrophic or discolored on 10% or less of the distal
`aspect, with minimally evident onycholysis and
`subungual hyperkeratosis. Negative mycology was
`defined as negative KOH wet mount and negative
`fungal culture.
`
`Safety
`Safety assessments were conducted at each
`visit, as was a physical examination evaluating
`the frequency and severity of application-site
`reactions:
`burning/stinging,
`induration/edema,
`oozing/crusting, pruritus, erythema, and scaling.
`Adverse events
`(AEs),
`treatment-emergent AEs
`(TEAEs), serious AEs, vital signs, laboratory parame-
`ters, and electrocardiographic parameters were
`monitored throughout the study.
`
`Statistics
`Efficacy parameters were evaluated in the
`intent-to-treat population, which included all
`randomized patients who received study treatment.
`Safety parameters were evaluated in all randomized
`patients who received at
`least 1 dose of study
`treatment and had at least 1 postbaseline assessment.
`Comparisons between treatment groups for the
`primary and secondary efficacy end points were
`made using the Cochran-Mantel-Haenszel
`test
`stratified by analysis. A last-observation-carried-
`forward approach was used to impute missing
`efficacy data. Two-sided hypothesis testing was
`conducted using a significance level of .05. AEs
`were classified using the Medical Dictionary for
`
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`J AM ACAD DERMATOL
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`
`Elewski et al 65
`
`Fig 2. Toenail onychomycosis. Patient disposition. ITT, Intent-to-treat.
`
`Regulatory Activities (Version 13.1, http://www.
`meddra.org). All safety parameters were summarized
`descriptively by treatment group.
`
`RESULTS
`Patients
`The disposition of patients (study 1, N = 594; study
`2, N = 604) is depicted in Fig 2. Demographic
`and clinical characteristics of
`the intent-to-treat
`population were similar between treatment groups
`and generally consistent across the 2 trials (Table I).
`
`Efficacy
`Tavaborole was significantly more effective than
`vehicle for all primary and secondary efficacy end
`points, and produced higher rates of negative culture
`and negative KOH at week 52 versus vehicle (Table
`II). A significantly greater proportion of patients
`achieved complete cure of the TGT at week 52
`with tavaborole versus vehicle in study 1 (6.5% vs
`0.5%; P = .001) and study 2 (9.1% vs 1.5%; P \.001).
`Rates of completely or almost clear nail at week 52
`with tavaborole were 26.1% and 27.5% in study 1 and
`study 2, respectively, versus 9.3% and 14.6% with
`vehicle (both P \ .001). Negative mycology rates
`
`with tavaborole were 31.1% and 35.9% in study 1 and
`study 2, respectively, versus 7.2% and 12.2% with
`vehicle (both P \ .001). Photographs illustrating a
`case with complete cure and a case of almost clear
`nail with negative mycology are shown in Fig 3.
`The onset of
`tavaborole clinical activity was
`evident by week 24 and generally increased through
`the end of treatment at week 48 and the final efficacy
`assessment at week 52 (Fig 4). Complete cure of the
`TGT was observed as early as week 24 in study 2 and
`at week 30 in study 1. Negative culture rates ranged
`from 95% at week 24 to 87% at week 52 in study 1 and
`94% at week 24 to 85% at week 52 in study 2.
`Negative KOH rates mirrored negative mycology
`data.
`
`Safety
`The incidence of TEAEs with tavaborole versus
`vehicle was similar in study 1 (64.4% vs 69.9%,
`respectively)
`and study 2 (57.5% vs 54.0%,
`respectively) (Table III). Most TEAEs in patients
`receiving tavaborole (95.5%) or vehicle (93.4%)
`were reported as mild or moderate in severity. The
`most common treatment-related application site
`TEAEs with tavaborole in the 2 trials combined
`
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`

`66 Elewski et al
`
`J AM ACAD DERMATOL
`JULY 2015
`
`Table I. Demographics and baseline characteristics of the intent-to-treat population
`
`Characteristic
`
`Tavaborole (n = 399)
`
`Vehicle (n = 194)
`
`Tavaborole (n = 396)
`
`Vehicle (n = 205)
`
`Study 1
`
`Study 2
`
`Age, y
`Mean (SD)
`Range
`Gender, n (%)
`Male
`Female
`Race
`White
`Black
`American Indian/Alaska Native
`Asian
`Native Hawaiian/Pacific Islander
`Other
`Country
`United States
`Canada
`Mexico
`No. of nontarget toenails $10%
`affected by onychomycosis
`Mean (SD)
`Range
`
`53.6 (12.5)
`18-88
`
`324 (81.2)
`75 (18.8)
`
`316 (79.2)
`19 (4.8)
`0 (0)
`2 (0.5)
`0 (0)
`62 (15.5)
`
`340 (85.2)
`—
`59 (14.8)
`
`53.4 (12.3)
`19-81
`
`158 (81.4)
`36 (18.6)
`
`152 (78.4)
`12 (6.2)
`0 (0)
`0 (0)
`0 (0)
`30 (15.5)
`
`164 (84.5)
`—
`30 (15.5)
`
`55.5 (11.5)
`20-81
`
`323 (81.6)
`73 (18.4)
`
`355 (89.6)
`21 (5.3)
`2 (0.5)
`11 (2.8)
`2 (0.5)
`5 (1.3)
`
`315 (79.5)
`81 (20.5)
`—
`
`55.4 (11.0)
`27-81
`
`174 (84.9)
`31 (15.1)
`
`183 (89.3)
`14 (6.8)
`1 (0.5)
`2 (1.0)
`1 (0.5)
`4 (2.0)
`
`165 (80.5)
`40 (19.5)
`—
`
`3.4 (2.8)
`0-9
`
`3.8 (2.7)
`0-9
`
`3.3 (2.8)
`0-9
`
`3.3 (2.6)
`0-9
`
`Table II. Efficacy end points at week 52
`
`End point
`
`Primary end point
`Complete cure of TGT*
`Secondary end points
`Completely CN or almost CN of TGT
`Negative mycology of TGT
`Completely or almost CN plus negative
`mycology of the TGT
`Other end points
`Negative culture of TGT
`Negative KOH of TGT
`Completely CN or almost CN of TGT
`with negative culture
`
`Tavaborole
`(n = 399)
`n (%)
`
`Study 1
`
`Vehicle
`(n = 194)
`n (%)
`
`Tavaborole
`(n = 396)
`n (%)
`
`P value
`
`Study 2
`
`Vehicle
`(n = 205)
`n (%)
`
`26 (6.5)
`
`1 (0.5)
`
`.001
`
`36 (9.1)
`
`3 (1.5)
`
`104 (26.1)
`124 (31.1)
`61 (15.3)
`
`18 (9.3)
`14 (7.2)
`3 (1.5)
`
`\.001
`\.001
`\.001
`
`109 (27.5)
`142 (35.9)
`71 (17.9)
`
`30 (14.6)
`25 (12.2)
`8 (3.9)
`
`P value
`
`\.001
`
`\.001
`\.001
`\.001
`
`347 (87.0)
`128 (32.1)
`98 (24.6)
`
`93 (47.9)
`17 (8.8)
`11 (5.7)
`
`—
`—
`—
`
`338 (85.4)
`147 (37.1)
`100 (25.3)
`
`105 (51.2)
`35 (17.1)
`19 (9.3)
`
`—
`—
`—
`
`CN, Clear nail; KOH, potassium hydroxide wet mount; TGT, target great toenail.
`*Completely CN and negative mycology.
`
`were exfoliation (2.7%), erythema (1.6%), and
`dermatitis (1.3%). The majority of TEAEs were
`considered not related or unlikely related to study
`treatment. The incidence of
`treatment-related
`TEAEs was higher with tavaborole versus vehicle
`in study 1 (8.8% vs 2.6%, respectively) and study 2
`(3.3% vs 0.5%, respectively) and was attributed to a
`higher rate of application-site reactions with tava-
`borole versus vehicle in study 1 (7.3% vs 0.5%,
`
`0%,
`(3.0% vs
`2
`study
`and
`respectively)
`respectively). Rates of discontinuations as a result
`of AEs occurred at similar rates between treatment
`groups (Table III).
`There were no deaths in either study. Serious AEs
`were reported in 19 patients (2.4%) who received
`tavaborole and 10 patients (2.5%) who received
`vehicle; none were considered treatment-related.
`Results of clinical laboratory and vital assessments
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`
`Elewski et al 67
`
`Fig 3. Toenail onychomycosis. Illustrative cases of complete cure of the target great toenail
`(top) and almost clear nail with negative mycology (bottom) after treatment with tavaborole for
`48 weeks. KOH, Positive potassium hydroxide wet mount.
`
`identify any safety signals, and no
`did not
`drug-related
`effects were
`observed
`on
`the
`electrocardiograms.
`
`DISCUSSION
`These findings from 2 phase-III trials demonstrate
`that once-daily tavaborole, without adjunctive
`debridement, is effective, safe, and well tolerated in
`the treatment of toenail onychomycosis. Tavaborole
`was significantly more effective than vehicle for all
`primary and secondary end points at week 52, with
`26% to 28% of patients achieving completely or
`almost clear nail; 31% to 36% achieving negative
`mycology; 7% to 9% achieving complete cure; and
`15% to 18% achieving completely or almost clear nail
`and negative mycology. The primary efficacy end
`point of complete cure (0% involvement of the nail
`plate and negative mycology) was chosen to enhance
`objectivity and is currently a regulatory standard for
`assessing the efficacy of antifungal agents for the
`treatment of toenail onychomycosis. The safety and
`efficacy of tavaborole was demonstrated in both adult
`and geriatric patients with a varied degree of disease
`severity, as the phase-III clinical trials enrolled patients
`
`aged 18 to 88 years with up to 60% clinical involvement
`of the TGT. Complete cure rates may not reflect the
`full clinical benefit of tavaborole. Although completely
`clear nail represents a definitive clinical cure, an
`(#10% affected)
`almost clear nail
`represents a
`clinically meaningful and successful outcome for
`many patients, and is likely the most realistically
`achievable outcome considering the residual nail
`defects that remain after the infection is cured.
`The number of TEAEs reported with tavaborole
`was low. Treatment-related TEAEs were localized
`to the application site;
`the most common were
`exfoliation, dermatitis, and erythema (1.3%-2.7%).
`Rates of discontinuations as a result of TEAEs were
`low and comparable with vehicle. Thus, tavaborole
`offers a favorable safety and tolerability profile.
`Tavaborole is a clear, colorless solution that is easy to
`apply, dries quickly, and does not require adjunctive
`debridement or removal of prior applications.
`The clinical efficacy and safety of tavaborole is
`supported by its ability to penetrate the nail plate,
`owing to its small size (152 d), hydrophilicity, and
`ability to retain pharmacologic antifungal activity in
`the presence of keratin.6 In ex vivo nail studies,
`
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`

`68 Elewski et al
`
`J AM ACAD DERMATOL
`JULY 2015
`
`Fig 4. Tavaborole efficacy in toenail onychomycosis. Change in efficacy end points over time
`from weeks 24 to 52. Each panel shows the percentage of patients achieving the end point at
`the indicated time point: complete cure (A); completely clear nail (CN ) or almost CN (B);
`negative mycology (C); completely or almost CN plus negative mycology (D); and negative
`culture (E). *P # .001 for tavaborole vs vehicle at week 52 for each of the end points assessed.
`Vertical lines indicate end of treatment at 48 weeks. Negative mycology was defined as negative
`potassium hydroxide wet mount and negative fungal culture. TGT, Target great toenail.
`
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`J AM ACAD DERMATOL
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`
`Table III. Summary of adverse events
`
`Adverse event
`Patients with $1 TEAEs
`Most common TEAEs*
`Tinea pedis
`Nasopharyngitis
`Upper respiratory tract infection
`Back pain
`Ingrowing nail
`Sinusitis
`Hypertension
`Influenza
`Headache
`Muscle strain
`y
`Most common application site TEAEs
`Exfoliation
`Dermatitis
`Erythema
`Pain
`Hematoma
`Discontinuations as a result of TEAEs
`
`Elewski et al 69
`
`Study 1
`
`Study 2
`
`Tavaborole (n = 396)
`n (%)
`
`Vehicle (n = 193)
`n (%)
`
`Tavaborole (n = 395)
`n (%)
`
`Vehicle (n = 202)
`n (%)
`
`255 (64.4)
`
`135 (69.9)
`
`227 (57.5)
`
`109 (54.0)
`
`42 (10.6)
`23 (5.8)
`20 (5.1)
`17 (4.3)
`14 (3.5)
`12 (3.0)
`11 (2.8)
`11 (2.8)
`10 (2.5)
`8 (2.0)
`
`16 (4.0)
`8 (2.0)
`7 (1.8)
`5 (1.3)
`2 (0.5)
`1 (0.3)
`
`35 (18.1)
`10 (5.2)
`8 (4.1)
`3 (1.6)
`1 (0.5)
`5 (2.6)
`8 (4.1)
`10 (5.2)
`5 (2.6)
`1 (0.5)
`
`1 (0.5)
`0 (0)
`0 (0)
`1 (0.5)
`1 (0.5)
`2 (1.0)
`
`53 (13.4)
`27 (6.8)
`18 (4.6)
`7 (1.8)
`6 (1.5)
`6 (1.5)
`11 (2.8)
`2 (0.5)
`11 (2.8)
`10 (2.5)
`
`5 (1.3)
`2 (0.5)
`6 (1.5)
`3 (0.8)
`3 (0.8)
`2 (0.5)
`
`25 (12.4)
`16 (7.9)
`12 (5.9)
`2 (1.0)
`0 (0)
`5 (2.5)
`4 (2.0)
`0 (0)
`7 (3.5)
`6 (3.0)
`
`0 (0)
`0 (0)
`0 (0)
`0 (0)
`2 (1.0)
`1 (0.5)
`
`TEAE, Treatment-emergent adverse event.
`*Occurring in $3% of patients in any treatment group.
`y
`Occurring in $1% of patients in any treatment group.
`
`tavaborole effectively penetrated the nail plate and
`achieved concentrations above the minimum fungi-
`cidal concentration.6,8 Tavaborole application once
`daily for 28 days to the toenails of patients with
`onychomycosis resulted in nail drug concentrations
`substantially above the minimum concentration
`required to inhibit 90% of isolates (minimal inhibi-
`tory concentration90) of T rubrum.8 Tavaborole nail
`concentrations were 20 times higher
`than the
`minimum fungicidal concentration against
`the
`dermatophytes 3 months after the end of treatment.
`Tavaborole demonstrated nail penetration 40-fold
`greater than ciclopirox after 14 days of application in
`a human cadaver fingernail model.10
`In conclusion,
`these studies demonstrate that
`tavaborole, a novel, first-in-class, boron-based
`pharmaceutical approved by the FDA for
`the
`treatment of toenail onychomycosis, has a favorable
`benefit-risk profile and is an attractive option for the
`treatment of onychomycosis of the toenail as a result
`of dermatophytes.
`
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`
`