1. Repatha ( Evolocumab) Praluent (Arilocumab)
SG-Amoateng

2. Repatha: Indication & Approval
Repatha, by AMGEN is FDA approved and indicated as:
1. An adjunct therapy to diet, and “maximally tolerated” statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C)
2. An adjunct to diet and other LDL-lowering therapies (eg. Statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C

3. Repatha: Drug Class & MOA
Repatha is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody.
It is a human monoclonal IgG2 directed against human PCSK9.
Binds to PCSK9 & inhibits circulating PCSK9 from binding to the LDL receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface.
By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

4. Repatha: Dosage & Formulation
Dosage Given
mg every 2 weeks or 420 mg every month for patients with HeHF or primary hyperlipidemia with established clinical atherosclerotic CVD.
mg once monthly for patients with HoFH.
Available as:
140 mg/mL solution in a single-use prefilled syringe for injection
140 mg/mL solution in a single-use prefilled SureClick® autoinjector
Use 3 Repatha injection within 30mins to get the 420 mg dose.

5. Repatha: Administration & Storage
Switching Regimen: Administer first dose of new regimen on the next schedule day of prior regimen.
Administer in Repatha SubQ into the abdomen, thigh, or upper arm area that are not tender, bruised, red, or indurated.
Do not shake
STORAGE
Keep Repatha refrigerated. Prior to use, allow to warm at room temp. for at least 30 minutes.
Alternatively keep at room temp (up to 25ºC (77ºF)) in original carton to be used within 30 days.
Do not freeze

6. Repatha: PD, PK
PD: maximum suppression of unbound PCSK9 occurred by 4 hours after administration.
PK:
Exhibits non-linear kinetics as a result of binding to PCSK9.
Following 140 mg or 420 mg dose, peak serum concentration were attained in 3-4 days with absolute bioavailability of 72%
VD 3.3(0.5) L
Half Life of 11 to 17 days
PK not affected by age, race, gender, and creatinine clearance.

7. Repatha: Dose Adjustment
Renal Impairment: Since monoclonal antibodies are not to be eliminated via renal pathways, renal dosing adjustments is not expected to impart PK.
Patients with eGFR < 30 mL/min/1.73 m2 have not been studied.
Hepatic Impairment: No dose adjustment is necessary. Although a single 140 mg subQ dose in patients with mild or moderate impairment had a 20-30% lower mean Cmax and 40-50% lower mean AUC compared to heathy patients.

8. Repatha: Side Effects & Adverse Effects
>10% Respiratory: Nasopharyngitis (6-11%)
Cardiovascular: HTN (3%)
CNS: Dizziness (4%), fatigue (2%)
GI: Gastroenteritis (3%-6%), Nausea (2%)
Genitourinary: Urinary tract infection (5%)
Hematologic & Oncologic: Bruise (1%)
Infection: Influenza (8% to 9%)
Neuromuscular & Skeletal: Myalgia (4%)
Local Site reaction (6%)

9. Repatha: Dosing & Age Usage
Teens/Adolescence Use: Safety and effectiveness were established in adolescence with HoHF from a placebo-controlled trail of 10 adolescence (ages 13-17)
Pediatric Use: Safety and effectiveness have not been studied yet.
Geriatric Use: Controlled studies in 1420 patients observed no differences in safety or effectiveness when compared to younger patients.

10. Repatha: Use in combination with Statins
Statins upregulates LDL receptors, and since Repatha also prevents the degradation of LDLR via PCSK9 pathway, it’s combination helps improves efficacy.
Treatment Group
LDL-C
Non-HDL-C
ApB
Total Cholesterol
Placebo every 2 weeks n(=42) 7 2 5 4
Repatha 140 mg every 2 weeks (n=105)
-64
-56
-49
-38
Mean difference from placebo (95%CI)
-71(-81, -61)
-58(-67, -49)
-55(-62, -47)
-42(-48, -36
Placebo once monthly (n=44) 3
Repatha 420 mg once monthly (n=105)
-58
-47
-46
-32
Mean difference from placebo (95% CI)
-63(-76, -50)
-52(-63,-41)
-49(-58,-39)
-36(-43, -28)
Table 1: Repatha’s effect on Lipid Parameters in Pt;s with ACVD on Atorvastatin 80mg, Rosuvastatin 40mg, or Simvastatin 40mg

11. Repatha: Use in combination with Statins

12. Repatha: Contraindications
Contraindicated in patients with serious hypersensitivity to evolocumag or any components of the formulation.

13. Repatha: Pregnancy & Lactation
Pregnancy: Effects have not been studied in humans. In animal models, no effects on pregnancy or neonatal/infant development was observed.
However since it’s used as adjunct to statin, which is Pregnancy category X it’s use might be limited or avoided until after pregnancy.
Lactation: There is no information regarding Repartha in human milk.

14. Repatha: How to…

15. Repatha: Counseling Pearls & Monitoring
Do not administer with other injectable drugs at the same injection site
Rotate the injection site with each injection
Monitor Lipid profile; in patients with HoFH, measure LDL-C levels 4 to 8 weeks after initiation. Degree of LDL-R will determine response to Repatha.
Missed Dose: If ,7days from usual day of administrations, administer ASAP and then resume the original schedule. If > 7 days, skip the missed dose and resume the normal schedule

16. Praluent: Indication & Approval
Praluent, from Sanofi, & Regeneron was approved by FDA in August 2015
Indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with Heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease , who require additional lowering of LDL- cholesterol (LDL-C)

17. Praluent : Drug Class & MOA
Praluent is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody.
Praluent is a human monoclonal antibody (IgG1)that binds to PCSK9 & inhibits circulating PCSK9 from binding to the LDL receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface.
By inhibiting the binding of PCSK9 to LDLR, Praluent increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
LDL-C is cleared from the circulation preferentially through the LDL receptor pathway.

18. Praluent : Dosage & Formulation
Available as prefilled subcutaneous injection syringes or prefilled pen
75 mg / mL pen every 2weeks as starting dose. (contains mouse protein (murine)(hamster)
May increase to 150 mg/mL every 2 weeks if an adequate response is not achieve within 4-8 weeks

19. Praluent: Administration & Storage
Administer Praluent Subcutaneously into the abdomen, thigh, or upper arm area that are not tender, bruised, red, or indurated.
Allow to come to room temperature 30 – 40 minutes prior to administrations.
Do not shake
Storage
Keep Praluent refrigerated at 36-46ºF (2-8ºC) in the outer carton to protect from light
Do not freeze

20. Praluent: PD, Pk
PD:
Proprotein Convertase sustilisin Kexin type 9 (PCSK9) suppression: occurs in 4 to 8 hours PK
Bioavailabity: SubQ: ~ 85%
Half-life elimination: SubQ: SS days, redued to 12 days when administered with a statin
Time to Peak: SubQ”: 3-7 days
VD: ~ 0.04 to 0.05 L/kg

21. Praluent: Dose Adjustment
Renal: Mild to Moderate: No dosage adjustment necessary
Severe Impairment: None provided by manugacturer’s labeling since it has not been studied. However not likely to be required since monoclonal antibodies are not know to be renally eliminated.
Hepatic: Mild to moderate: No dosage adjustment necessary
Severe Impairment; None provided by manufacturer’s labeling. No studies yet.

22. Praluent: Side Effects & Adverse Effects
GI: Diarrhea (5%)
Hepatic: liver enzyme disorder (3%), Increased Transaminases (>3x ULN;2%)
Hypersensitivity: Hypersensitivity reaction
Infection: Influenza
Local: Injection site reaction (7%)
Neuromuscular & skeletal: Myalgia (4%), muscle spasm (3%)
Respiratory: cough (3%)
<1% (limited to important or

23. Praluent: Contraindications
Contraindicated in patients with serious hypersensitivity to alirocumab or any components of the formulation.

24. Praluent: Pregnancy and Lactation
Pregnancy: Information not yet available and ADE events were not observed in animal reproduction studies. However, IgG molecules are known to cross the placenta, with increasing amounts during the second and third trimesters of pregnancy.
Lactation: Information not available, but IgG molecules ae known to be present in breast milk.

25. Praluent: How to…

26. Praluent: Counseling Pearls & Monitoring
Avoid combination with Belimumab. Risk X
Monitor LDL-C within 4 -8 weeks of initiation

27. $$ CO$t $$: Both Dosage Form Repatha Praluent Auto Injector
140 mg/mL (1mL): $650.77
75 mg/mL (1mL):
Same
150 mg/mL (1mL):
Solution Prefilled-syringe

29. Credits!! https://www.praluenthcp.com/mechanism-of-action
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