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Eucrisa™ - Crisaborole
Manufacturer: Anacor
Pharmaceuticals, Inc.
FDA Approval Date: 12/14/2016
Maria Buckner, PharmD Candidate
Eucrisa™ - crisaborole
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Eucrisa™ -
(crisaborole)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Eucrisa™ (crisaborole)
Eucrisa™ - crisaborole
Clinical Application
• Indications:
• Topical treatment of mild to moderate
atopic dermatitis (AD) in patients 2 years
of age and older
• Place in therapy:
• First line option in place of topical
steroids and calcineurin inhibitors for the
treatment of mild to moderate AD
Eucrisa [package insert].
Eucrisa™ - crisaborole
Clinical Application
• Contraindications:
• Known hypersensitivity
• Warnings:
• None
• Precautions:
• None
Eucrisa [package insert].
Eucrisa™ - crisaborole
Clinical Application
• Pregnancy:
• No human data available
• No adverse effects seen with oral
administration of up to 600 mg/kg/day in
rat and rabbit studies
• Lactation:
• No human data available
Eucrisa [package insert].
Eucrisa™ - crisaborole
Drug Facts
• Pharmacology:
• Topical phosphodiesterase 4 (PDE-4)
inhibitor
• PDE-4 inhibition results in increased
intracellular cAMP levels
• Exact mechanism is not well defined
but is thought to work by reducing
pro-inflammatory cytokines thought
to cause signs and symptoms of AD
Eucrisa [package insert].
Eucrisa™ - crisaborole
Drug Facts
• Pharmacokinetics:
A
Limited; systemic concentrations at
steady state (Cmax) on Day 8
D
97% bound to human plasma proteins
M
Metabolized into 2 inactive metabolites
via hydrolysis and oxidation
E
Renal excretion of metabolites
Eucrisa [package insert].
Eucrisa™ - crisaborole
Drug Interactions
• Drug Interactions – Object Drugs:
• Weak inhibitor of CYP1A2 and 2B6
• Moderate inhibitor of CYP2C8 and 2C9
• Trial with warfarin as CYP2C9
substrate showed no drug interaction
potential
Eucrisa [package insert].
Eucrisa™ - crisaborole
Drug Interactions
• Drug Interactions – Precipitant Drugs:
• None identified
Eucrisa [package insert].
Eucrisa™ - crisaborole
Adverse Effects
• Common Adverse Effects:
(crisaborole%) [placebo%]
• Application site pain (4%) [1%]
• Serious Adverse Effects:
• None
Eucrisa [package insert].
Eucrisa™ - crisaborole
Monitoring Parameters
• Efficacy Monitoring:
• Clearing/improvement of AD from baseline
• Toxicity Monitoring:
• Very limited systemic exposure
• Inactive metabolites result in low risk of
toxicity
• Theoretically, extremely high systemic
concentrations can lead to GI toxicities
Eucrisa [package insert].
Eucrisa™ - crisaborole
Prescription Information
• Dosing: Twice daily application of 2%
topical ointment in a thin layer to
affected areas
• Cost: – Not yet available
Eucrisa [package insert].
Eucrisa™ - crisaborole
Literature Review
• Efficacy and safety of crisaborole
ointment for the topical treatment of AD in
children and adults (AD-301 and AD-302)
• Study Design
• Two identically designed, vehicle-controlled,
randomized, double-blind phase 3 trials
• Patient assigned 2:1 to crisaborole or
vehicle treatment twice daily for 28 days
• N=1522 between both studies
Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4.
Eucrisa™ - crisaborole
Literature Review
Inclusion Criteria
• Age 2 years and older
• Clinical diagnosis of AD
• 5% or more treatable
body surface area
involvement
• Baseline ISGA score of
mild (2) or moderate (3)
Exclusion Criteria
• Previous use of biologic
therapy or systemic
corticosteroids within 28
days
• Topical corticosteroid or
topical calcineurin
inhibitor use within 14
days
• Active skin infection
Paller AS,et al. J Am Acad Dermatol. 2016;75:494-503.e4.
Eucrisa™ - crisaborole
Literature Review
• Patient Characteristics
AD-301
AD-302
Crisaborole
n=503
Vehicle
n=256
Crisaborole
n=513
Vehicle
n=250
Mean Age
12.0
12.4
12.6
11.8
Age Range
2-65
2-63
2-79
2-79
Sex, %
Male
Female
43.5
56.5
44.1
55.9
45.0
55.0
44.8
55.2
Baseline ISGA, %
Mild (2)
Moderate (3)
39.0
61.0
36.3
63.7
38.4
61.6
40.0
60.0
% BSA, mean
18.8
18.6
17.9
17.7
Characteristic
% BSA, range
5-95
5-90
5-95
5-90
Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4.
Eucrisa™ - crisaborole
Literature Review
• Primary Efficacy Endpoint
• Success in ISGA score at day 29 defined
as clear (0) or almost clear (1) with a 2grade or more improvement from baseline
• Secondary Efficacy Endpoint
• Pruritus severity
• Primary Safety Endpoint
• Treatment related adverse events
Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4.
Eucrisa™ - crisaborole
Literature Review
• Efficacy Results
• Clear/almost clear with ≥ 2-grade improvement
(primary)
• AD-301: 32.8% vs 254.%, P = 0.038
• AD-302: 31.4% vs 18.0%, P < 0.001
• Improvement in pruritus (secondary)
• Pooled data, days 8,15,22: P < 0.001; day 29:
P = 0.002
• Safety Result
• Application site pain (4.4%) [1.2%]
Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4.
Eucrisa™ - crisaborole
Literature Review
• Conclusions
• Crisaborole is a promising new option for
mild to moderate AD targeting the
underlying mechanism of the disease
• Improvement was seen in all efficacy
measures over vehicle alone including
pruritus
• Crisaborole has a favorable safety profile
with low incidence of adverse effects
Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4.
Eucrisa™ - crisaborole
Summary
• Eucrisa ™ (crisaborole) is a non-steroidal, topical
anti-inflammatory PDE-4 inhibitor ointment for the
treatment of mild to moderate atopic dermatitis in
patients ≥ 2
• A thin layer should be applied to the affected area
BID
• The most common side effect is burning or stinging
at the application site
• Eucrisa ™ has low systemic absorption, quick
metabolism and a low rate of adverse effects, making
it a safe alternative topical steroids and calcineurin
inhibitors for the treatment of mild to moderate AD
Eucrisa™ - crisaborole
References
1.
www.myeucrisa.com
2.
Eucrisa [package insert]. Palo Alto, CA: Anacor
Pharmaceuticals Inc.; 2016.
3.
Include ALL article references in standard
format: Paller AS, et al. Efficacy and safety of
crisaborole ointment, a novel, nonsteroidal
phosphodiesterase 4 inhibitor for the topical
treatment of atopic dermatitis in children and
adults. J Am Acad Dermatol. 2016;75:494-503.e4.