1. Manufacturer: Amgen Inc FDA Approval Date: August 27, 2015
Repatha™ - Evolocumab
Manufacturer: Amgen Inc
FDA Approval Date: August 27, 2015

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

3. Repatha™ - Evolocumab Clinical Application
Indications:
Adjunct to diet in adults on maximally tolerated statin therapy with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease that need additional lowering of LDLc
Adjunct to diet in adults on other LDL therapies with homozygous hypercholesterolemia who need additional lowering of LDLc
Repatha [package insert].

4. Repatha™ - Evolocumab Clinical Application
Contraindications:
Serious hypersensitivity to evolocumab or any component of the formulation
Repatha [package insert].

5. Repatha™ - Evolocumab Clinical Application
Warnings and Precautions
Allergic reactions like rash and urticaria
Discontinue treatment if serious allergic reaction
Repatha [package insert].

6. Repatha™ - Evolocumab Clinical Application
Pregnancy:
Animal studies show it crosses the placenta during 2nd and 3rd trimester
Lactation:
IgG is present in human milk; data shows it doesn’t enter neonatal and infant circulation in substatial amounts
Repatha [package insert].

7. Repatha™ - Evolocumab Drug Facts
Pharmacology:
Human monoclonal IgG2 antibody, binds to proprotein convertase substilsin/kexin 9 (PCSK9) and inhibits it from binding to LDL receptor preventing PCSK9 mediated degradation and increasing number of LDLRs available to clear LDL from blood
Repatha [package insert].

8. Repatha™ - Evolocumab Drug Facts
Pharmacokinetics: A
Absolute bioavailability 72% D
Mean ss volume of distribution 3.3 L M
Proteolytic degradation E
Estimated half life 11 – 17 days
Repatha [package insert].

9. Repatha™ - Evolocumab Drug Interactions
Drug Interactions – Precipitant Drugs:
In patient on a high intensity statin there was a 20% decrease in the Cmax and AUC of evolocumab
Repatha [package insert].

10. Repatha™ - Evolocumab Adverse Effects
Common Adverse Effects:
Evolocumab
Placebo
Nasopharyngitis
10.5
9.6
Upper respiratory tract infection
9.3
6.3
Influenza
7.5
Injection site reactions
5.7
5.0
Cough
4.5
3.6
Repatha [package insert].

11. Repatha™ - Evolocumab Monitoring Parameters
Efficacy Monitoring:
HoFH: measure LDL-C 4-8 weeks after initiation of evolocumab
Toxicity Monitoring:
Signs and symptoms of hypersensitivity or adverse reaction
Repatha [package insert].

12. Repatha™ - Evolocumab Prescription Information
Dosing:
HeFH or primary hyperlipidemia with CVD: 140 mg SQ every 2 weeks or 420 mg SQ once monthly
HoFH: 420 mg SQ once monthly
Cost: $14,000 per year
Medscape –accessed 1/11/2016
Repatha [package insert].

13. Repatha™ - Evolocumab Literature Review
DESCARTES 52 week trial
Purpose: To evaluate safety and efficacy of a 52 week treatment with evolocumab
Design: randomized, double blind phase 3
88 centers in 9 countries
Blom DJ et. al. N Engl J Med: 370 (19);

14. Repatha™ - Evolocumab Literature Review
Inclusion Criteria
Exclusion Criteria
18-75 yo
LDL-C ≥ 75 mg/dL
Fasting TG ≤ 400 mg/dL
Heart Failure
Recent MI
Recent or planned revascularization procedure
Uncontrolled HTN
Hyper/hypothyroidism
Moderate to severe renal dysfunction
Active liver disease or hepatic dysfunction
Blom DJ et. al. N Engl J Med: 370 (19);

15. Repatha™ - Evolocumab Literature Review
Intervention: 420 mg evolocumab or placebo monthly
Primary endpoint: Percent change from baseline of LDL-C at week 52
Secondary endpoint:
Absolute change in LDL-C at week 52
% change in LDL-C at week 12
% of pts with LDL-C < 70 mg/dL at week 52
Blom DJ et. al. N Engl J Med: 370 (19); .

16. Repatha™ - Evolocumab Literature Review
Baseline Characteristics:
Placebo
(N = 302)
Evolocumab
(N = 599)
Age
Male
White
56.7
46.4%
82.1%
55.9
48.4%
79.5%
CV risk factors
BMI
DM2
Smoker
HTN
30.5
13.9%
15.9%
49.3%
29.9
10.4%
14.5%
48.2%
LDL-C
/-21.6
104.2+/-22.
Blom DJ et. al. N Engl J Med: 370 (19); .

17. Repatha™ - Evolocumab Literature Review
Results
Placebo
Evolocumab
Mean LDL-C at baseline
104 +/- 21.6
/- 22.1
No of pts at week 52
264
542
Mean % LDL change
at week 52
6.8 +/- 1.8
/- 1.2
Mean Chol vs placebo
/- 1.9
50.9 +/- 1.4
Pts with LDL-C < 70
6.4%
82.3%
Blom DJ et. al. N Engl J Med: 370 (19); .

18. Repatha™ - Evolocumab Literature Review
Safety endpoints
Adverse Event
Placebo
Evolocumab
Any
Serious
Death
74.2%
4.3%
74.8%
5.5%
0.3% (2)
Common adverse events
Nasopharyngitis
Upper resp. tract infection
Influenza
Cough
Injection Site Erythema
9.6%
6.3%
3.6%
2.0%
10.5%
9.3%
7.5%
4.5%
2.7%
Blom DJ et. al. N Engl J Med: 370 (19); .

19. Repatha™ - Evolocumab Literature Review
Trial conclusion:
Evolocumab reduced LDL-C levels by 57% as compared with placebo at 52 weeks in patients at risk for coronary diseases receiving lipid lowering therapy
Blom DJ et. al. N Engl J Med: 370 (19); .

20. Repatha ™ - Evolocumab Summary
Repatha™ ,evolocumab, is a PCSK9 inhibitor that reduces LDL-C by increasing the number of available LDL-Rs
Evolocumab is indicated as adjunct treatment with HeFH, HoFH or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C
Suggested subcutaneous dosing is 140 mg every 2 weeks or 420 mg every month
Common adverse drug reactions include respiratory and injection-site reactions
Suggested monitoring: LDL-C 4 to 8 weeks after starting therapy in patients with HoFH

21. Repatha™ - Evolocumab References
Repatha [evolocumab] package insert. Amgen Inc. (Thousand Oaks, CA): Aug. 2015; m?setid=709338ae-ab8f-44a9-b7d5-abaabec3493a
Blom DJ et. al. A 52 week placebo controlled trial of Evolocumab in hyperlipidemia. N Engl J Med : 370 (19);