Transcript 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.