Download praluent

Praluent® - alirocumab
Manufacturer: Sanofi and
Regeneron Pharmaceuticals
FDA Approval Date: July 24, 2015
Praluent® - alirocumab
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Praluent®
(alirocumab)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Praluent®
(alirocumab)
Praluent® - alirocumab
Clinical Application
• Indications:
• Treatment of adults with heterozygous
familial hypercholesterolemia or clinical
atherosclerotic cardiovascular disease
• Place in therapy:
• Those who need additional LDL lowering
despite maximally tolerated statin
Praluent [package insert].
Praluent® - alirocumab
Clinical Application
• Contraindications:
• Serious hypersensitivity reaction
• Black Box warnings: none
• Warning and Precautions:
• Hypersensitivity reactions
• Potential for immunogenicity
Praluent [package insert].
Praluent® - alirocumab
Clinical Application
• Pregnancy:
• Category C
• Lactation:
• Unknown if excreted in human breast
milk
• Human IgG is present in human milk, but
data suggest breast milk IgG antibodies
do not enter infant circulation in
substantial amounts
Praluent [package insert].
Praluent® - alirocumab
Drug Facts
• Pharmacology:
• Human monoclonal antibody that inhibits
PCSK9
• PCSK9 is a protease that degrades LDL
receptors on hepatocytes.
• LDL receptors clear circulating LDL
Praluent [package insert].
Praluent® - alirocumab
Drug Facts
• Pharmacokinetics:
A
D
M
E
F = 85%
tmax 3-7 days
Vd = 0.04-0.05 L/kg
Expected to degrade to small peptides and
amino acids
Does not affect CYP450, PGP, or OATP
T1/2 17-20 days
Praluent [package insert].
Praluent® - alirocumab
Drug Interactions
• Drug Interactions – Precipitant Drugs:
• Statin reduces half-life of alirocumab to
12 days
• Not clinically significant
Praluent [package insert].
Praluent® - alirocumab
Adverse Effects
Praluent
Placebo
Allergic Reactions
8.6%
7.8%
Injection Site Reactions
7.2%
5.1%
Influenza
UTI
Diarrhea
Bronchitis
Myalgia
5.7%
4.6%
4.8%
4.6%
4.7%
4.4%
4.3%
4.4%
4.2%
3.4%
Praluent [package insert].
Praluent® - alirocumab
Monitoring Parameters
• Efficacy Monitoring:
• LDL-C within 4 to 8 weeks
Praluent [package insert].
Praluent® - alirocumab
Prescription Information
• Dosing:
• Initial dose: 75 mg SC every 2 weeks
• Max dose: 150 mg SC every 2 weeks
• Cost: NY Times – accessed 8/11/15
• 75 mg or 150 mg injection: $14,600/year
Praluent [package insert].
Praluent® - alirocumab
Prescription Information
• Administration:
• Warm to room temperature for 30 to 40
min prior to use
• Inject SC into stomach, upper arm, or
thighs
• Rotate injection sites
Praluent [package insert].
Praluent® - alirocumab
Literature Review
ODYSSEY LONG TERM
• Purpose: to obtain longer-term data n
safety and efficacy of alirocumab
• Design: randomized, double blind,
phase 3 trial
• 320 sites in 27 countries
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Literature Review
Inclusion Criteria
• Age >18 years
• LDL-C <70 mg/dl
• Heterozygous familial
hypercholesterolemia
• Established CHD or
CHD risk equivalent
• LDL-C >70 mg/dl
Exclusion Criteria
• Statin other than
simvastatin, atorvastatin, or
rosuvastatin
• Homozygous familial
hypercholesterolemia
• CHF Class III or IV
• High dose statin therapy or
maximum tolerated dose for • BP >180/110
>4 weeks before screening
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Literature Review
• Intervention: alirocumab 150 mg q2 weeks
vs. placebo
• Primary endpoint: percent change in LDL-C
from baseline to week 24
• Secondary endpoint: percent change in
other lipoprotein variables
• Post-hoc analysis: rate of adjudicated
major adverse CV events between groups
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Literature Review
• Baseline Characteristics
Alirocumab (N=1553)
Placebo (N=788)
Age
60.4
60.6
Male
983 (63.3%)
474 (60.2%)
White
1441 (92.8%)
730 (92.6%)
CV history and risk factors:
• BMI
• Heterozygous FH
• CHD
• CHD risk equivalent
• Type 2 DM
• Current smoker
30.2
276 (17.8%)
1055 (67.9%)
639 (41.1%)
542 (34.9%)
325 (20.9%)
30.5
139 (17.6%)
552 (70.1%)
323 (41.0%)
267 (33.9%)
159 (20.2%)
Lipid-modifying medications:
• Any statin
• High-dose statin
1552 (>99.9%)
727 (46.8%)
787 (99.9%)
368 (46.7%)
LDL-C
122.7
121.9
Triglycerides
132.0
135.0
HDL-C
49.8
50.0
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Literature Review
• Results
Alirocumab
(N=1530)
Placebo
(N=780)
LS Mean
Difference
P-value
Baseline LDL-C
122.8
122.0
--
--
Absolute level at wk 24
48.3
118.9
--
--
Percent change from
baseline to wk 24
-61.0%
0.8%
-61.9%
<0.001
Percent change from
baseline to wk 78
-52.4%
3.6%
-56.0%
<0.001
LDL<70 in very high risk
patients or LDL<100 in
high risk patients
80.7%
8.5%
--
<0.001
LDL<70 regardless of risk
79.3%
8.0%
--
<0.001
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Literature Review
• Safety endpoints
Adjudicated major adverse CV
events in post hoc analysis
Death from CHD
Nonfatal MI
Fatal or nonfatal ischemic stroke
Adverse effects:
• General allergic reaction
• Injection site reaction
• Myalgia
• Neurologic event
Alirocumab
(N=1550)
Placebo
(N=788)
P-value
27 (1.7%)
26 (3.3%)
0.02
4 (0.3%)
7 (0.9%)
0.26
14 (0.9%)
18 (2.3%)
0.01
9 (0.6%)
2 (0.3%)
0.35
156 (10.1%)
91 (5.9%)
84 (5.4%)
65 (4.2%)
75 (9.5%)
33 (4.2%)
23 (2.9%)
35 (4.4%)
0.71
0.10
0.006
0.83
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Literature Review
• Conclusions:
• Alirocumab significantly reduces LDL-C
when added to maximum tolerated statin
therapy in patients with heterozygous
familial hypecholesterolemia and patients
with CHD or CHD risk equivalent
• In the post-hoc analysis, there was
evidence of reduction in the rate of CV
events with alirocumab
Robinson JG, et al. N Engl J Med. 2015;372:1489-99
Praluent® - alirocumab
Summary
• Praluent® (alirocumab) is the first-in-class PCSK9
inhibitor that reduces LDL-C
• Indicated for the treatment of adults with
heterozygous familial hypercholesterolemia or
clinical ASCVD, who require additional LDL-C
lowering despite diet and maximally tolerated
statin therapy
• Dose is 75 or 150 mg every 2 weeks given as a SC
injection
• The most common AEs observed include
hypersensitivity reactions
• LDL-C should be monitored within 4-8 weeks
Praluent® - alirocumab
References
1. www.praluent.com
2. Praluent [package insert]. Bridgewater, NJ: Sanofi and
Regeneron; 2015.
3. Robinson JG, Farnier M, Krempf M, et al. Efficacy and
safety of alirocumab in reducing lipids and
cardiovascular events. N Engl J Med. 2015;372:1489-99.
4. Pollack A. The New York Times Website. New Drug
Sharply Lowers Cholesterol, but it’s Costly.
http://www.nytimes.com/2015/07/25/business/usapproves-drug-that-can-sharply-lower-cholesterollevels.html. Published July 24, 2015. Accessed August
11, 2015.