1. Eucrisa™ - Crisaborole
Manufacturer: Anacor Pharmaceuticals, Inc.
FDA Approval Date: 12/14/2016
Maria Buckner, PharmD Candidate

2. Eucrisa™ - crisaborole Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Eucrisa™ - (crisaborole)
Effectively educate patients on the purpose, proper use and potential adverse effects of Eucrisa™ - (crisaborole)

3. 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].

4. Eucrisa™ - crisaborole Clinical Application
Contraindications:
Known hypersensitivity
Warnings:
None
Precautions:
Eucrisa [package insert].

5. 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:
Eucrisa [package insert].

6. 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].

7. 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].

8. 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].

9. Eucrisa™ - crisaborole Drug Interactions
Drug Interactions – Precipitant Drugs:
None identified
Eucrisa [package insert].

10. Eucrisa™ - crisaborole Adverse Effects
Common Adverse Effects: (crisaborole%) [placebo%]
Application site pain (4%) [1%]
Serious Adverse Effects:
None
Eucrisa [package insert].

11. 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].

12. 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].

13. 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: e4.

14. Eucrisa™ - crisaborole Literature Review
Inclusion Criteria
Exclusion 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)
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: e4.

15. Eucrisa™ - crisaborole Literature Review
Patient Characteristics
AD-301
AD-302
Characteristic
Crisaborole
n=503
Vehicle
n=256
n=513
n=250
Mean Age
12.0
12.4
12.6
11.8
Age Range
2-65
2-63
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
% BSA, range
5-95
5-90
Paller AS, et al. J Am Acad Dermatol. 2016;75: e4.

16. Eucrisa™ - crisaborole Literature Review
Primary Efficacy Endpoint
Success in ISGA score at day 29 defined as clear (0) or almost clear (1) with a 2-grade 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: e4.

17. 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: e4.

18. 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: e4.

19. 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

20. Eucrisa™ - crisaborole References
Eucrisa [package insert]. Palo Alto, CA: Anacor Pharmaceuticals Inc.; 2016.
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: e4.