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: Appropriately recommend Eucrisa™ - (crisaborole) 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: 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: 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 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;75:494-503.e4.

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;75:494-503.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 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;75:494-503.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 www.myeucrisa.com 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;75:494-503.e4.