PiPeline Plus
Dyslipidemia Blockbuster Therapies Are on the Horizon Rinki Patel, PharmD; and Kunj Gohil, PharmD, RPh
D
yslipidemia is recognized as a prominent risk factor for cardiovascular disease (CVD); every 1% decrease in cholesterol levels is linked to a 2% decrease in coronar y heart disease risk.1,2 This disease continues to present a large economic burden in the U.S., with approximately 1.33 million patients diagnosed in 2013.1,3 Given that the number of patients is expected to rise in the coming years, the acute coronary syndrome market is projected to expand globally from $12.3 billion to $43.4 billion in sales by 2023.3 Dyslipidemia is defined by elevations in low-density lipoprotein-cholesterol Dr. Patel is a Post-Doctoral Fellow with Medical Services at MediMedia Managed Markets in Yardley, Pennsylvania. Dr. Gohil is Central Services Manager with Medical Services at MediMedia Managed Markets.
(LDL-C) and triglyceride concentrations, in addition to low levels of high-density lipoprotein-cholesterol (HDL-C).4 Statins are a universally established therapy due to their ability to dramatically reduce LDL-C levels and lower CVD risk. However, there is a gap in clinical practice when it comes to achieving LDL-C goals for many patients, and 5% to 10% of people cannot tolerate statin treatment.1,2 Specifically, patients with familial hypercholesterolemia are more likely to suffer from statin resistance and require additional effective therapies.2 Future therapies include the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a new class of agents with blockbuster potential that are expected to launch this year and may address the needs unmet by statins. These self-injectable monoclonal antibodies work by increasing the liver’s
ability to filter LDL-C from circulation.2 Additional novel cholesterol-lowering therapies with specific effects on LDL-C and/or HDL-C levels are also on the horizon. These agents are expected to revolutionize the dyslipidemia market.
REFERENCES 1.
2. 3. 4.
Schultz AB, Chen CY, Burton WN, et al. The burden and management of dyslipidemia: practical issues. Popul Health Manag 2012:302–308. GlobalData. PharmaPoint Acute Coronary Syndrome: US Drug Forecast and Market Analysis to 2023. July 2014. GlobalData. EpiCast Report: Dyslipidemia Epidemiology Forecast to 2023. October 2014. Musunuru K. Atherogenic dyslipidemia: cardiovascular risk and dietary intervention. Lipids 2010;45(10):907–914. ■
Future Therapies Drug Manufacturer PCSK9 Inhibitors Repatha (evolocumab) Amgen
Praluent (alirocumab) Sanofi/Regeneron
Bococizumab Pfizer
Status
Regimen Information
Pivotal Studies
Expected Approval
Anticipated Peak Year Sales/Pricing
Phase 3
140 mg once every two weeks via SC injection or 420 mg once every four weeks via SC injection
PROFICIO
2015
Phase 3
150 mg once every two weeks via SC injection
ODYSSEY
2016
Phase 2/3
One dose once every two weeks via SC injection
SPIRE
2018
$10.2 billion by 2023; using the onceeveryfourweeks regimen, it is expected that one dose of evolocumab will cost twice as much as one dose of Humira, which is used every two weeks $5.2 billion by 2023; expected to be about 5% lower than current pricing for Humira, which costs $1,921 per 40mg injection $2.2 billion by 2023; expected to be about 10% lower than current pricing for Humira
ACCELERATE
2017
DEFINE REVEAL
2018
Cholesteryl Ester Transfer Protein Inhibitors Evacetrapib Phase 3 130 mg once daily orally Eli Lilly Anacetrapib Merck
Phase 3
100 mg once daily orally
SC = subcutaneous Sources: FDA; GlobalData; company websites; ClinicalTrials.gov
402 P&T
®
• June 2015 • Vol. 40 No. 6
$1.1 billion by 2023; expected to be about 30% higher than current cost of Crestor $538.3 million by 2023; expected to be priced about 25% higher than Crestor’s current cost of about $8.23 per pill
Pipeline Plus Current Therapies a Drug Approval Indication b Regimen Cost of Course of Manufacturer Date Information c Therapy per Year d 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Livalo (pitavastatin) 2009 Hyperlipidemia; mixed dyslipidemia 1 mg to 4 mg daily $2,606 Kowa Pharmaceuticals Crestor (rosuvastatin) 2003 Hyperlipidemia; mixed dyslipidemia; 5 mg to 40 mg daily $3,004 AstraZeneca pediatric HeFH; HoFH (adjunct therapy) Altoprev (lovastatin) 2002 Primary prevention of CAD; 20 mg to 60 mg daily $6,764 Shionogi CAD; hyperlipidemia Lipitor (atorvastatin) 1997 Prevention of CV disease; 10 mg to 80 mg daily $2,652–$3,783 Pfizer hyperlipidemia (generic, $134–$702) Hypercholesterolemia; mixed 20 mg to 80 mg daily $2,230–$4,460 Lescol (fluvastatin) 1993 dyslipidemia; secondary prevention (generic, $1,377–$2,759) Novartis of CV disease Zocor (simvastatin) 1992 Hyperlipidemia; HeFH; reductions in 5 mg to 40 mg daily $1,235–$2,888 Merck risk of CHD mortality and CV events (generic, $1,028–$1,814) Pravachol (pravastatin) 1991 Prevention of CV disease; 40 mg daily $2,478 Bristol-Myers Squibb hyperlipidemia (generic, $1,206) Selective Cholesterol Absorption Inhibitor Zetia (ezetimibe) 2002 Hyperlipidemia; HoFH; 10 mg daily $3,142 Merck homozygous sitosterolemia Niacin/Nicotinic Acid Niaspan (niacin) 1997 Primary hyperlipidemia; 500 mg $1,981 AbbVie mixed hyperlipidemia (generic, $1,546) Fibrates Fibricor (fenofibric acid) 2009 Hyperlipidemia; mixed dyslipidemia; 105 mg daily $1,503 Mutual Pharmaceutical severe hypertriglyceridemia (generic, $1,096) 135 mg daily $3,084 Trilipix (fenofibric acid) 2008 Mixed dyslipidemia; severe hyper triglyceridemia; hypercholesterolemia (generic, $1,947) AbbVie Triglide (fenofibrate) 2005 Hypercholesterolemia; mixed dyslipid 160 mg daily $2,916 Shionogi emia; severe hypertriglyceridemia (generic, $867) Tricor (fenofibrate) 2004 Hypercholesterolemia; mixed dyslipid 145 mg daily $3,235 AbbVie emia; severe hypertriglyceridemia (generic, $2,091) Lopid (gemfibrozil) 1981 Hyperlipidemia; reduction 1,200 mg daily $3,473 Pfizer in risk of developing CHD (generic, $798) Combination Therapies Liptruzet (ezetimibe/atorvastatin) 2013 Hyperlipidemia; HoFH 10/10 mg to 10/80 mg $2,409 Merck daily Simcor (niacin ER/simvastatin) 2008 Hypercholesterolemia 500/20 mg daily $1,981 AbbVie Caduet (amlodipine/atorvastatin) 2004 Hypertension; CAD; prevention 5/10 mg to 10/80 mg daily $3,602–$4,927 Pfizer of CV disease; hyperlipidemia Vytorin (ezetimibe/simvastatin) 2004 Primary hyperlipidemia; 10/10 mg to 10/40 mg daily $3,113 Merck HoFH (adjunct therapy) Advicor (niacin ER/lovastatin) 2001 Hypercholesterolemia 500/20 mg daily $2,831 AbbVie a
This list is not all-inclusive; additional therapies may be available for this disease state. Abbreviated indication provided; for full indication, please refer to prescribing information. c Regimens based on the recommended dosage and maintenance phases from prescribing information; typical doses and titration schedules may vary based on patient-specific requirements. d Costs calculated using average wholesale price and regimen provided and rounded to the nearest dollar. b
Sources: Red Book; Drugs@FDA; and prescribing information for all medications CAD = coronary artery disease; CHD = coronary heart disease; CV = cardiovascular; ER = extended release; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia
Vol. 40 No. 6 • June 2015 • P&T 403 ®
Dyslipidemia Blockbuster Therapies Are on the Horizon Rinki Patel, PharmD; and Kunj Gohil, PharmD, RPh
D
yslipidemia is recognized as a prominent risk factor for cardiovascular disease (CVD); every 1% decrease in cholesterol levels is linked to a 2% decrease in coronar y heart disease risk.1,2 This disease continues to present a large economic burden in the U.S., with approximately 1.33 million patients diagnosed in 2013.1,3 Given that the number of patients is expected to rise in the coming years, the acute coronary syndrome market is projected to expand globally from $12.3 billion to $43.4 billion in sales by 2023.3 Dyslipidemia is defined by elevations in low-density lipoprotein-cholesterol Dr. Patel is a Post-Doctoral Fellow with Medical Services at MediMedia Managed Markets in Yardley, Pennsylvania. Dr. Gohil is Central Services Manager with Medical Services at MediMedia Managed Markets.
(LDL-C) and triglyceride concentrations, in addition to low levels of high-density lipoprotein-cholesterol (HDL-C).4 Statins are a universally established therapy due to their ability to dramatically reduce LDL-C levels and lower CVD risk. However, there is a gap in clinical practice when it comes to achieving LDL-C goals for many patients, and 5% to 10% of people cannot tolerate statin treatment.1,2 Specifically, patients with familial hypercholesterolemia are more likely to suffer from statin resistance and require additional effective therapies.2 Future therapies include the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a new class of agents with blockbuster potential that are expected to launch this year and may address the needs unmet by statins. These self-injectable monoclonal antibodies work by increasing the liver’s
ability to filter LDL-C from circulation.2 Additional novel cholesterol-lowering therapies with specific effects on LDL-C and/or HDL-C levels are also on the horizon. These agents are expected to revolutionize the dyslipidemia market.
REFERENCES 1.
2. 3. 4.
Schultz AB, Chen CY, Burton WN, et al. The burden and management of dyslipidemia: practical issues. Popul Health Manag 2012:302–308. GlobalData. PharmaPoint Acute Coronary Syndrome: US Drug Forecast and Market Analysis to 2023. July 2014. GlobalData. EpiCast Report: Dyslipidemia Epidemiology Forecast to 2023. October 2014. Musunuru K. Atherogenic dyslipidemia: cardiovascular risk and dietary intervention. Lipids 2010;45(10):907–914. ■
Future Therapies Drug Manufacturer PCSK9 Inhibitors Repatha (evolocumab) Amgen
Praluent (alirocumab) Sanofi/Regeneron
Bococizumab Pfizer
Status
Regimen Information
Pivotal Studies
Expected Approval
Anticipated Peak Year Sales/Pricing
Phase 3
140 mg once every two weeks via SC injection or 420 mg once every four weeks via SC injection
PROFICIO
2015
Phase 3
150 mg once every two weeks via SC injection
ODYSSEY
2016
Phase 2/3
One dose once every two weeks via SC injection
SPIRE
2018
$10.2 billion by 2023; using the onceeveryfourweeks regimen, it is expected that one dose of evolocumab will cost twice as much as one dose of Humira, which is used every two weeks $5.2 billion by 2023; expected to be about 5% lower than current pricing for Humira, which costs $1,921 per 40mg injection $2.2 billion by 2023; expected to be about 10% lower than current pricing for Humira
ACCELERATE
2017
DEFINE REVEAL
2018
Cholesteryl Ester Transfer Protein Inhibitors Evacetrapib Phase 3 130 mg once daily orally Eli Lilly Anacetrapib Merck
Phase 3
100 mg once daily orally
SC = subcutaneous Sources: FDA; GlobalData; company websites; ClinicalTrials.gov
402 P&T
®
• June 2015 • Vol. 40 No. 6
$1.1 billion by 2023; expected to be about 30% higher than current cost of Crestor $538.3 million by 2023; expected to be priced about 25% higher than Crestor’s current cost of about $8.23 per pill
Pipeline Plus Current Therapies a Drug Approval Indication b Regimen Cost of Course of Manufacturer Date Information c Therapy per Year d 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Livalo (pitavastatin) 2009 Hyperlipidemia; mixed dyslipidemia 1 mg to 4 mg daily $2,606 Kowa Pharmaceuticals Crestor (rosuvastatin) 2003 Hyperlipidemia; mixed dyslipidemia; 5 mg to 40 mg daily $3,004 AstraZeneca pediatric HeFH; HoFH (adjunct therapy) Altoprev (lovastatin) 2002 Primary prevention of CAD; 20 mg to 60 mg daily $6,764 Shionogi CAD; hyperlipidemia Lipitor (atorvastatin) 1997 Prevention of CV disease; 10 mg to 80 mg daily $2,652–$3,783 Pfizer hyperlipidemia (generic, $134–$702) Hypercholesterolemia; mixed 20 mg to 80 mg daily $2,230–$4,460 Lescol (fluvastatin) 1993 dyslipidemia; secondary prevention (generic, $1,377–$2,759) Novartis of CV disease Zocor (simvastatin) 1992 Hyperlipidemia; HeFH; reductions in 5 mg to 40 mg daily $1,235–$2,888 Merck risk of CHD mortality and CV events (generic, $1,028–$1,814) Pravachol (pravastatin) 1991 Prevention of CV disease; 40 mg daily $2,478 Bristol-Myers Squibb hyperlipidemia (generic, $1,206) Selective Cholesterol Absorption Inhibitor Zetia (ezetimibe) 2002 Hyperlipidemia; HoFH; 10 mg daily $3,142 Merck homozygous sitosterolemia Niacin/Nicotinic Acid Niaspan (niacin) 1997 Primary hyperlipidemia; 500 mg $1,981 AbbVie mixed hyperlipidemia (generic, $1,546) Fibrates Fibricor (fenofibric acid) 2009 Hyperlipidemia; mixed dyslipidemia; 105 mg daily $1,503 Mutual Pharmaceutical severe hypertriglyceridemia (generic, $1,096) 135 mg daily $3,084 Trilipix (fenofibric acid) 2008 Mixed dyslipidemia; severe hyper triglyceridemia; hypercholesterolemia (generic, $1,947) AbbVie Triglide (fenofibrate) 2005 Hypercholesterolemia; mixed dyslipid 160 mg daily $2,916 Shionogi emia; severe hypertriglyceridemia (generic, $867) Tricor (fenofibrate) 2004 Hypercholesterolemia; mixed dyslipid 145 mg daily $3,235 AbbVie emia; severe hypertriglyceridemia (generic, $2,091) Lopid (gemfibrozil) 1981 Hyperlipidemia; reduction 1,200 mg daily $3,473 Pfizer in risk of developing CHD (generic, $798) Combination Therapies Liptruzet (ezetimibe/atorvastatin) 2013 Hyperlipidemia; HoFH 10/10 mg to 10/80 mg $2,409 Merck daily Simcor (niacin ER/simvastatin) 2008 Hypercholesterolemia 500/20 mg daily $1,981 AbbVie Caduet (amlodipine/atorvastatin) 2004 Hypertension; CAD; prevention 5/10 mg to 10/80 mg daily $3,602–$4,927 Pfizer of CV disease; hyperlipidemia Vytorin (ezetimibe/simvastatin) 2004 Primary hyperlipidemia; 10/10 mg to 10/40 mg daily $3,113 Merck HoFH (adjunct therapy) Advicor (niacin ER/lovastatin) 2001 Hypercholesterolemia 500/20 mg daily $2,831 AbbVie a
This list is not all-inclusive; additional therapies may be available for this disease state. Abbreviated indication provided; for full indication, please refer to prescribing information. c Regimens based on the recommended dosage and maintenance phases from prescribing information; typical doses and titration schedules may vary based on patient-specific requirements. d Costs calculated using average wholesale price and regimen provided and rounded to the nearest dollar. b
Sources: Red Book; Drugs@FDA; and prescribing information for all medications CAD = coronary artery disease; CHD = coronary heart disease; CV = cardiovascular; ER = extended release; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia
Vol. 40 No. 6 • June 2015 • P&T 403 ®
