IDR 69596 Profile of Efinaconazole in The Treatment of Onchomycosis 060115
IDR 69596 Profile of Efinaconazole in The Treatment of Onchomycosis 060115
IDR 69596 Profile of Efinaconazole in The Treatment of Onchomycosis 060115
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open access to scientific and medical research
Review
Shari R Lipner
Richard K Scher
Department of Dermatology, Weill
Cornell Medical College, New York,
NY, USA
Abstract: Efinaconazole 10% topical solution is a new triazole recently approved for the
treatment of onychomycosis. It inhibits fungal lanosterol 14-demethylase in the ergosterol biosynthesis pathway, has potent antifungal activity against dermatophytes, as well as activity against
Candida spp. and non-dermatophyte molds, and showed promising results in clinical trials. This
review summarizes the mechanism of action, in vitro and in vivo data, clinical trials, safety, and
quality-of-life data of efinaconazole as it applies to the treatment of onychomycosis.
Keywords: efinaconazole, Jublia, onychomycosis, fungal infection, nail infection
Introduction
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http://dx.doi.org/10.2147/IDR.S69596
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Mechanism of action
Fungal cell membranes are composed of the structural
compound ergosterol, which maintains membrane fluidity, creates a permeability barrier, and is essential for
fungal cell viability. It is believed that loss of ergosterol
affects cell membrane integrity and function and inhibits
fungal cell growth.19,20
Using an ergosterol biosynthesis assay, it was shown
that efinaconazole inhibited ergosterol biosynthesis in both
Trichophyton mentagrophytes and Candida albicans, and
was more active than two comparator drugs, itraconazole
and clotrimazole. T. mentagrophytes hyphal morphology
exhibited changes that were dependent on the efinaconazole
concentration (Table 1). The authors concluded that the
mechanism of action of efinaconazole is through inhibition
of the ergosterol pathway, likely via 14-demethylase, with
secondary degenerative changes.21
Efinaconazole concentration:
0.110 g/mL
Shortening of interseptal
distance
Globular swelling
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Pharmacokinetics
Pharmacokinetic data were analyzed in healthy volunteers
(n=10) and patients with severe onychomycosis ($80% surface area of both great toenails) (n=20) in two single-center
open-label studies (Phase I). Efinaconazole was applied to the
healthy volunteers by staff on day 1, and then on days 410,
for a total of eight doses and applied to the onychomycosis
patients daily for 28days.36
The data showed that efinaconazole is absorbed slowly,
lacks an elimination phase,36 and is metabolized through
both oxidation and reduction, yielding an H3 metabolite.23
The concentration of efinaconazole and its metabolite was
approximately 3.6-fold and 5.8-fold greater on day 10 than on
day 1 in healthy volunteers and 6.8-fold and 30.5-fold greater
on day 28 than day 1 in onychomycosis patients, indicating
that the drug accumulates with successive applications.
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Exclusion criteria
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Table 3 Results from the four treatment arms in efinaconazole Phase II trial
Efinaconazole
10% solution
Efinaconazole
5% solution
Vehicle
22.2%
83.3%
61%
25.6%
87.2%
64%
15.8%
86.8%
55%
9.1%
N/A
23%
67%
69%
N/A
32%
Vehicle (n=214)
(study 1)
Vehicle (n=202)
(study 2)
17.8%
55.2%
26.4%
35.7%
5.0
3.3%
16.8%
7.0%
11.7%
1.6
15.2%
53.4%
23.4%
31.0%
3.8
5.5%
16.9%
7.5%
11.9%
0.9
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Nasopharyngitis
Upper respiratory tract infection
Sinusitis
Eczema
Headache
Vehicle (n=213)
(study 1)
Vehicle (n=200)
(study 2)
78 (11.9%)
38 (5.8%)
30 (4.6%)
22 (3.4%)
15 (2.3%)
25 (11.5%)
13 (6.1%)
4 (1.9%)
7 (3.3%)
5 (2.3%)
63 (11.0%)
35 (6.1%)
17 (3.0%)
25 (4.4%)
15 (7.5%)
11 (5.5%)
5 (2.5%)
7 (3.5%)
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QoL studies
Onychomycosis may have substantial bearing on physical
and psychological well-being, by disrupting daily life, negatively impacting QoL, and causing pain and difficulty with
ambulation.53 Patients with onychomycosis have reported
embarrassment, low self-esteem, and problems with social
interaction due to their disease.54 Subjects who were part of
the Phase III studies with efinaconazole were also assessed
for a change in QoL with treatment using a self-administered
OnyCOE-t questionnaire at baseline and at weeks 24 and
52. The authors found that efinaconazole was significantly
more effective than vehicle in improving QoL. In addition,
there was a significant difference in the treatment satisfaction
scores between those subjects who showed clinical improvement and those who did not improve.55
Approval
Efinaconazole 10% solution (Valeant Pharmaceuticals
International) was approved by Health Canada for the treatment of mild-to-moderate onychomycosis in October 2013.56
A regulatory application for approval of efinaconazole for
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Conclusion
Efinaconazole 10% topical solution is a new and promising
treatment for mild-to-moderate DLSO onychomycosis. It
has potent antifungal activity against dermatophytes, as
well as activity against Candida spp. non-dermatophyte
molds. It is appropriate for onychomycosis therapy in a
broad range of patients due to its favorable side-effect
profile, low rate of treatment-related AEs, and negligible
risk for drugdrug interactions, and as there is no need for
blood monitoring.
Disclosure
Dr Lipner has no conflicts of interest to disclose. Dr Scher is
a consultant, investigator, and speaker for multiple companies
including consultant and speaker for Valeant. The authors
report no other conflicts of interest in this work.
References
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