1. Manufacturer: Celgene Corporation FDA Approval Date: 9/23/14
Otezla® - apremilast
Manufacturer: Celgene Corporation
FDA Approval Date: 9/23/14

2. Otezla®- apremilast Clinical Application
Indications:
Treatment of moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy
Treatment of active psoriatic arthritis in adults
Place in therapy:
Oral alternative to Methotrexate and retinoids

3. Otezla®- apremilast Clinical Application
Contraindications:
Hypersensitivity to apremilast or any component of the formulation
Warnings:
Depression, suicidal ideation, and mood changes have been reported
May cause weight loss
Precautions:
Systemic exposure increased in patients with CrCl <30 ml/min

4. Otezla®- apremilast Clinical Application
Pregnancy:
Category C
Lactation:
Excretion in breast milk is unknown, use caution

5. Otezla®- apremilast Drug Facts
Pharmacology:
Inhibits phosphodiesterase-4 (PDE4) preventing it from degrading cyclic adenosine monophosphate (cAMP) to AMP resulting in increased cAMP levels intracellularly. Cyclic AMP down regulates inflammatory response through several inflammatory mediators.
Specific Mediators: nitric oxide synthase, TNF-alpha, IL-23, IL-10
Specific mechanisms by which this drug exerts therapeutic effects in psoriatic arthritis patients is not well defined
PDE4 degrades cAMP to AMP, cAMP down-regulates inflammatory response

6. Otezla®- apremilast Drug Facts
Pharmacokinetics: A
Well absorbed; ~73% bioavailability D
Vd 87 L; 68% protein bound M
Hepatic: Major CYP3A4
Minor CYP1A2 and CYP2A6 E
t1/2 6-9h; 58% in urine, 39% in feces

7. Otezla®- apremilast Drug Interactions
Drug Interactions – Object Drugs:
None

8. Otezla®- apremilast Drug Interactions
Drug Interactions – Precipitant Drugs:
Bosentan: ↓ concentration
Strong CYP3A4 inducers: ↓concentration
Dabrafenib: ↓ concentration
Deferasirox: ↓ concentration
Siltuximab: ↓ concentration
St. John’s Wort: ↓ concentration
Tocilizumab: ↓ concentration

9. Otezla®- apremilast Adverse Effects
Common Adverse Effects:
Serious Adverse Effects:
Diarrhea (9%) [2%]
Nausea (9%) [3%]
Headache (6%) [2%]
URI (4%) [2%]
Nasopharyngitis (3%) [2%]
Vomiting (3%) [0.4%]
Abdominal pain (2%) [0.2%]
Major SE difference depending on indication
Weight loss is a 5-10% reduction in 16 weeks
Weight Loss (10-12%) [3-5%]
Depression (1%) [ %]

10. Otezla®- apremilast Monitoring Parameters
Efficacy Monitoring:
Signs and Symptoms of Psoriasis/psoriatic arthritis within 3 months of initiation
Toxicity Monitoring:
SCr: 3 months and annually
Weight Loss: 3 months
Depression: 3 months

11. Otezla®- apremilast Prescription Information
Dosing: 30 mg BID
Titration:
Cost: UpToDate.com Accessed 11/03/2014
Starter Pack: $1012
30 mg Tablets #60: $2250
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6 AM PM 10 mg
10 mg
20 mg
30 mg

12. Otezla®- apremilast Literature Review
Phase 3 Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) Trial
Randomized, placebo controlled study
Included 504 patients from 13 countries
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

13. Otezla®- apremilast Literature Review
Phase 1: 24 weeks
1:1:1 randomization to receive either apremilast 30 mg BID, apremilast 20 mg BID, or placebo
Phase 2: 28 weeks
Patients who received placebo in Phase 1 were randomized 1:1 to receive apremilast 20 mg BID or apremilast 30 mg BID
Patients receiving apremilast in Phase 1 remained on that dose
52 weeks total
This slide is for contextual purposes
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

14. Otezla®- apremilast Literature Review
Primary Endpoint: Proportion of patients with 20% improvement in modified ACR response criteria at week 16
Secondary Endpoints:
Change from baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at week 16
Improvement in S/Sx of PsA, physical function, and psoriasis at 24 weeks
Look up details on these scoring tools
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

15. Otezla®- apremilast Literature Review
Baseline Characteristics
Parameter
Placebo
Apremilast 20 mg BID
Apremilast 30 mg BID
Age (years)
51.1
48.7
51.4
BMI
31.1
30.9
30.6
Mean duration of PsA (years)
7.3
7.2
8.1
Mean HAQ-DI (0-3)
1.2
Psoriasis involvement of BSA 3% or more (n) 68 77 82
Mean PASI Score (0-72)
9.1
7.4
9.2
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

16. Otezla®- apremilast Literature Review
Intent to treat analysis
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

17. Otezla®- apremilast Literature Review
Intent to treat analysis
A reduction in this score is associated with improvement
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

18. Otezla®- apremilast Literature Review
Psoriasis Area and Severity Index
Kavanaugh A, et al. Ann Rheum Dis 2014;73:

19. Otezla®- apremilast Summary
Apremilast is an effective oral agent for the treatment of psoriasis and psoriatic arthritis
Maintenance Dose: 30 mg BID with dosing adjustment for CrCl <30 ml/min
Weight and signs of depression must be monitored for as these are potentially serious adverse effects

20. Otezla®- apremilast References
Otezla (apremilast) package insert. Celgene Corporation. Sept
Apremilast. Lexicomp Drug Information. Accessed through UpToDate. Accessed on Nov 3, 2014.
Kavanaugh A, et al. Ann Rheum Dis 2014;73:
Papp KA, et al. JEADV 2013,27, e