New Drug Introduction: Repatha™ / Evolocumab
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Black Box Warnings
Warnings and
Precautions
Pregnancy/Lactation
Pharmacokinetics
Human monoclonal IgG2 antibody that binds to proprotein convertase subtilisin
kexin 9 (PCSK9) and inhibits circulating PCSK9 from binding to the low density
lipoprotein receptor (LDL-R), preventing PCSK-9 mediated LDL-R degradation
and allowing LDL-R to recycle back to the liver cell surface. By inhibiting the
binding of PCSK9 to LDLR, evolocumab increases the number of LDL-Rs
available to clear LDL from the blood thus lowering LDL-C levels
Amgen
August 27, 2015
Indicated as an adjunct to diet and;
- Maximally tolerated statin therapy for treatment of adults with heterozygous
familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular
disease (CVD) who require additional lowering of LDL-C
- Other LDL-lowering therapies in patients with homozygous
hepercholesterolemia (HoFH) who need additional lowering of LDL-C
Serious hypersensitivity to evolocumab or any component of the formulation
None
Allergic reactions like rash and urticarial have occurred. Discontinue treatment
if signs or symptoms of serious allergic reactions occur, and treat according to
standard of care and monitor until signs and symptoms resolve
No human studies. Animal studies show it crosses the placenta. Previous
experience indicates monoclonal antibodies cross the placenta during 2nd and
3rd trimester. Even though IgG is present in human milk data shows it does not
enter neonatal and infant circulation in substantial amounts. Risks vs. benefits
should be considered.
A – Estimated absolute bioavailability 72%, median Cmax: 3-4 days
D – Mean steady state volume of distribution 3.3 L (SD 0.5)
M – Non-saturable proteolytic pathway
E – Half life estimated to be 11 to 17 days
Drug Interactions –
Object Drugs
An approximately 20% decrease in the Cmax and AUC of evolocumab
was observed in patients co-administered with a high-intensity statin
regimen. This difference is not clinically meaningful and does not impact
dosing recommendations.
Adverse Effects
-Nasopharyngitis (10.5) [ 9.6]
Cough (4.5) [3.6]
-Upper resp tract infection (9.3) [6.3]
Injection site reaction (5.7) [5.0]
-Influenza (7.5) [6.3]
Homozygous familial hypercholesterolemia: measure LDL-C 4-8 weeks after
initiation of evolocumab
Signs and symptoms of hypersensitivity reaction or adverse reaction
No laboratory monitoring suggested
HeFH or primary hyperlipidemia with CVD: 140 mg subcutaneously every 2
weeks or 420 mg subcutaneously once monthly.
Homozygous familial hypercholesterolemia: 420 mg once monthly
No adjustment needed in mild to moderate impairment.
No data available in severe renal impairment
No adjustment needed in mild to moderate impairment.
No data available in severe hepatic impairment
Treatment(%) Placebo[%]
Monitoring Efficacy
Monitoring Toxicity
Dosing
Renal Adjustment
Hepatic Adjustment
Cost: Source: Medscape.com, date accessed 01/11/2016
Dose(s)
Repatha™ – Evolocumab
140 mg, 420 mg injection
Repatha™ - Evolocumab

75 mg, 150 mg injection
Praluent - Alirocumab
1 year
$14,000
$14,600
Summary
 Repatha™, evolocumab, a human monoclonal IgG2 antibody, is a PCSK9 inhibitor that
reduces LDL-C by increasing the number of available LDL-Rs
 Evolocumab is indicated as adjunct treatment in adults with heterozygous familial
hypercholesterolemia, homozygous familial hypercholesterolemia 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
References:
1. https://www.repatha.com
2. Repatha [evolocumab] package insert. Amgen Inc. Aug. 2015.
3. Evolocumab Facts and Comparisons online.factsandcomparisons.com (Accessed
January 2015).
4. Blom DJ et. al. A 52 week placebo controlled trial of Evolocumab in hyperlipidemia. N
Engl J Med. 2014: 370 (19); 1809-1819
Date Prepared: 01/11/2016
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Persida Tahiri, Pharm.D. Candidate, UNC Eshelman School of Pharmacy