2013 REPORT Biopharmaceutical research companies are developing 215 medicines for two of the leading causes of death in Ameri- cans—heart disease and stroke. Medi- cines have helped cut deaths from these diseases by 30 percent between 2001 and 2011, and in 2008 stroke dropped to the fourth leading cause of death after being the third for more than 50 years. This progress is in large part due to innovative medicines. Despite this progress, heart disease and stroke persist as key public health chal- lenges. According to the American Heart Association, every 39 seconds an Ameri- can dies from cardiovascular disease, and more than 83 million Americans have at least one type of the disease. These diseases cost our society more than $312 billion a year. The medicines in development include: 30 for heart failure, 29 for lipid disorders (such as high cholesterol), 19 for stroke, and 17 each for high blood pressure and ischemic disorders. Many of the potential medicines use cutting-edge technologies and new scientific approaches, such as: • A gene therapy that uses a patient’s own cells to treat heart failure. • A medicine that blocks the transfer of good (HDL) cholesterol to bad (LDL). • A genetically-engineered medicine that dissolves clots to treat stroke. All of the medicines are either in clinical trials or awaiting review by the Food and Drug Administration. A glossary of terms begins on page 24. Links to sponsor company websites provide more informa- tion on the potential products. For information on the current innovative products in the pipeline for cardiovascular disease and the value of medicines for patients and our healthcare system, please see Medicines in Development for Heart Disease and Stroke 2013—Overview. Biopharmaceutical Research Companies Are Developing More Than 200 Medicines for Cardiovascular Disease MEDICINES IN DEVELOPMENT Heart Disease and Stroke A Report on Cardiovascular Disease PRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES Lipid Disorders Hypertension 30 17 17 Ischemic Disorders 29 Heart Failure Stroke 19 Application Submitted Phase III Phase II Phase I Medicines in Development For Heart Disease and Stroke 83.6 Million Americans Suffer From Cardiovascular Disease More Than 700,000 Die Each Year
Transcript
2013 R
EPORT
Biopharmaceutical research companies are developing 215 medicines for two of the leading causes of death in Ameri-cans—heart disease and stroke. Medi-cines have helped cut deaths from these diseases by 30 percent between 2001 and 2011, and in 2008 stroke dropped to the fourth leading cause of death after being the third for more than 50 years. This progress is in large part due to innovative medicines.
Despite this progress, heart disease and stroke persist as key public health chal-lenges. According to the American Heart Association, every 39 seconds an Ameri-can dies from cardiovascular disease, and more than 83 million Americans have at least one type of the disease. These diseases cost our society more than $312 billion a year.
The medicines in development include: 30 for heart failure, 29 for lipid disorders (such as high cholesterol), 19 for stroke, and 17 each for high blood pressure and ischemic disorders. Many of the potential
medicines use cutting-edge technologies and new scientific approaches, such as:
• A gene therapy that uses a patient’s own cells to treat heart failure.
• A medicine that blocks the transfer of good (HDL) cholesterol to bad (LDL).
• A genetically-engineered medicine that dissolves clots to treat stroke.
All of the medicines are either in clinical trials or awaiting review by the Food and Drug Administration. A glossary of terms begins on page 24. Links to sponsor company websites provide more informa-tion on the potential products.
For information on the current innovative products in the pipeline for cardiovascular disease and the value of medicines for patients and our healthcare system, please see Medicines in Development for Heart Disease and Stroke 2013—Overview.
Biopharmaceutical Research Companies Are Developing More Than 200 Medicines for Cardiovascular Disease
MeDiCines in DevelopMenT
Heart Disease and strokeA Report on Cardiovascular Disease
presented by america’s biopharmaceutical research companies
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Application Submitted
Phase III
Phase II
Phase I
Medicines in Development For Heart Disease and stroke
83.6 million americans suffer From cardiovascular disease
Medicines in Development heart disease and stroke 2013 3
medicines in development for heart disease and stroke
Adjunctive Therapies, Revascularization
Product Name Sponsor Indication Development Phase
ATryn®
antithrombin(recombinant)(Orphan Drug)
rEVO BiologicsFramingham, MA
heparin resistance in patients undergoing coronary artery bypass graft (CABG) surgery (see also hypertension)--------------------------------------heparin resistance in patients undergoing CABG surgery in neonates
acute decompensated heart failure(see also atherosclerosis, hypertension)--------------------------------------reduction of cardiovascular death/hospitalization in chronic heart failure patients
intravenous bolus-only administration in patients undergoing coronary artery stenting
in clinical trialswww.canyonpharma.com
edoxaban(oral factor Xa inhibitor)
Daiichi SankyoParsippany, NJ
venous thromboembolism (prevention), embolism/stroke in patients with atrial fibrillation (prevention)
Phase IIIwww.daiichisankyo.com
Medicines in Development Heart Disease and Stroke 201320
Medicines in Development for Heart Disease and Stroke
Eliquis®
apixabanBristol-Myers SquibbPrinceton, NJPfizerNew York, NY
prevention of venous thromboembolism, treatment of venous thrombosis
Phase IIIwww.bms.comwww.pfizer.com
GCC-4401 Green CrossYongin, South Korea
coronary thrombosis Phase I completedwww.greencross.co.kr
Iprivask®
desirudin SC(subcutaneous)
Canyon PharmaceuticalsColumbia, MD
thromboembolism in patients with suspected heparin-induced thrombocytopenia (prevention and treatment), venous thromboembolism in high-risk surgical and medical patients (prevention)
secondary prevention of cardiovascular and cerebrovascular disease in patients at risk for aspirin-induced ulcers
application submittedwww.pozen.com
Other
Product Name Sponsor Indication Development Phase
Medicines in Development Heart Disease and Stroke 201322
PA32540(aspirin 325mg/omeprazole 40mg)
POZENChapel Hill, NC
secondary prevention of cardiovascular and cerebrovascular disease in patients at risk for aspirin-induced ulcers
application submittedwww.pozen.com
RX-10001(lipid modulator)
Resolvyx PharmaceuticalsCambridge, MA
cardiovascular disorders Phase I completedwww.resolvyx.com
T89(herbal medicine product)
Tasly PharmaceuticalsRockville, MD
angina pectoris Phase IIIwww.tasly.com
Vascana™nitroglycerin topical
MediQuest TherapeuticsMaple Valley, WA
Raynaud’s disease Phase IIIwww.mqti.com
Vyndaqel®tafamidis meglumine
PfizerNew York, NY
transthyretin familial amyloid cardiomyopathy
Phase IIIwww.pfizer.com
Xarelto®
rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJ
prevention of cardiovascular events secondary to chronic heart failure, coronary or peripheral artery disease, or atrial fibrillation(Fast Track)(see also acute coronary syndrome, thrombosis)
Phase IIIwww.bayerpharma.comwww.janssenrnd.com
Medicines in Development for Heart Disease and Stroke
Other
Product Name Sponsor Indication Development Phase
The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” data-base based on the latest information. Report current as of May 22, 2013. The medicines in this report include medicines being developed by U.S. based companies conducting trials in the United States and abroad, PhRMA-member companies conducting trials in the United States and abroad, and foreign companies conducting clinical trials in the United States. The information in this report may not be comprehensive. For more specific information about a particular product, contact the individual company directly or go to www.clinicaltrials.gov. The entire series of Medicines in Development is available on PhRMA’s website.
A publication of PhRMA’s Communications & Public Affairs Department. (202) 835-3460
Pharmaceutical Research and Manufacturers of America • 950 F Street, NW, Washington, DC 20004
Medicines in Development heart disease and stroke 2013 23
Glossary
adjunctive therapy—Auxiliary treatment that is secondary to the main treatment.
angina pectoris—Chest pain, usually caused by “myocardial ischemia,” a low supply of oxygen to the heart muscle resulting from hardening, narrowing, and sometimes spasm of the coronary arteries.
application submitted—An application for marketing has been submitted by the company to the Food and Drug Admin-istration (FDA).
arrhythmia—Abnormal heart rhythm, usually detected by an electrocardio-gram. Arrhythmias can be caused by several factors, such as coronary artery disease, heart valve problems or hyper-thyroidism.
arteriosclerosis obliterans—An alter-native term for peripheral vascular disease.
atherosclerosis—A common disease in which deposits of plaque containing calcium and fatty substances, such as cholesterol, are formed within the inner layers of the arteries. It is a condition that progresses over decades, chiefly affecting the arteries of the heart, brain and extremities. Its complications include heart attacks and strokes.
atrial fibrillation—Very fast electrical discharge patterns that make the heart’s atria contract extremely rapidly, which causes the ventricles to contract faster and less efficiently than normal. As a result, inadequate amounts of blood are pumped out of the heart, blood pressure falls, and heart failure may occur.
bypass graft—A vein or artery graft that bypasses blockage in an artery.
cardiomyopathy—A type of heart disease in which the heart muscle is abnormally enlarged, thickened and/or stiffened. As a result, the heart muscle’s ability to pump blood is usually impaired.
cardiovascular—Of or relating to the heart and blood vessels.
coronary artery disease—A condition caused by atherosclerosis of the arteries that supply the heart.
critical limb ischemia (Cli)—CLI is a severe obstruction of the arteries that seriously decreases blood flow to the extremities (arms, hands, legs, feet) and has progressed to the point of severe pain and even skin ulcers or sores. The pain, called “rest pain,” caused by CLI can wake up a person at night. CLI is a very severe condition of peripheral arterial disease and needs comprehen-sive treatment by a vascular surgeon or specialist.
deep vein thrombosis—Blood clotting within the deep-lying veins, often in the legs or pelvic veins.
dyslipidemia—A condition marked by abnormal concentrations of lipids or lipoproteins in the blood.
embolism—The obstruction of a blood vessel by a foreign substance or a blood clot. Foreign substances that can cause embolism include an air bubble, amni-otic fluid, a globule of fat, a clump of bacteria, chemicals, and drugs. Blood clots are the most common cause of embolism. The term “embolus” refers to the substance or clot that is obstructing the blood vessel, while “embolism” refers to the process by which that happens.
Fast Track—A process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The status is assigned by the U.S. Food and Drug Administration. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. Gener-ally, determining factors include whether the drug will have an impact on such factors as survival, day-to-day function-ing, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be
potentially superior to existing therapy. Once a drug receives Fast Track designa-tion, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
genotype—The genetic constitution (genome) of a cell, an individual, or an organism. The genotype of a person is her or his genetic makeup. It can pertain to all genes or to a specific gene.
HDl—High-density lipoprotein, some-times called “good cholesterol.”
heart attack (myocardial infarction)—A part of the heart muscle (myocardium) dies as a result of blood and oxygen deprivation.
heart failure—The end result of many different types of heart disease. The heart cannot pump blood out normally. This results in congestion (water and salt retention) in the lungs, swelling in the extremities, and reduced blood flow to body tissues.
hemodialysis—A medical procedure that uses a special machine (a dialysis ma-chine) to filter waste products from the blood and to restore normal constituents to it.
hypercholesterolemia—The presence of an abnormally large amount of cho-lesterol in the cells and plasma of the circulating blood.
hyperlipidemia—A group of metabolic disorders characterized by high levels of lipids (fatty substances, including choles-terol) in the blood. Hyperlipidemia is a risk factor for accelerated atherosclerosis and premature heart attacks.
hypertension (high blood pressure)—Persistent elevation of blood pressure above the normal range while the heart is in systolic (contracting) or diastolic (relaxed) mode. Uncontrolled, chronic
Medicines in Development heart disease and stroke 201324
Glossary
hypertension strains the heart, damages arteries and creates a greater risk of heart attack, stroke and kidney problems.
hypertriglyceridemia—An elevated triglyceride concentration in the blood.
hypotension—A sudden fall in blood pressure. It may be caused by hypovo-lemia resulting from the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or prolonged bed rest. The disorder may be associated with Addison’s disease, atherosclerosis (build-up of fatty deposits in the arter-ies), diabetes, and certain neurological disorders. Symptoms, which generally occur after sudden standing, include diz-ziness, light-headedness, blurred vision, and the temporary loss of consciousness.
imaging agent—A substance used to enhance images of organs and spaces in the body.
intermittent claudication—The most prominent symptom of peripheral arte-rial disease (PAD). It occurs in one-third to one-half of PAD patients. Claudica-tion refers to the pain that occurs in PAD patients when they exercise, particularly during walking, which is relieved only by rest. Leg pain occurs in one leg in 40 percent of patients and in both legs in 60 percent of patients.
ischemia—Insufficient supply of blood to an organ or tissue, which can cause or-gan damage such as an ischemic stroke.
lipids—A group of fatty substances that includes triglycerides (the principal forms of fat in body fat), phospholipids (im-portant constituents of cell membranes), and sterols (such as cholesterol).
peripheral vascular disease—The obstruction of blood supply to the ex-tremities, particularly the legs, caused by atherosclerosis.
peT imaging—Positron emission tomog-raphy.
phase i—Safety testing and pharmaco-logical profiling in humans.
phase ii—Effectiveness testing in humans.
phase iii—Extensive clinical trials in humans.
preeclampsia—A condition in pregnant women characterized by high blood pressure and high levels of protein in urine.
pulmonary hypertension—High blood pressure in the arteries supplying the lungs due to increased resistance to blood flow through the lungs.
Raynaud’s disease—A circulatory disor-der caused by insufficient blood supply to the hands and feet, resulting in cya-nosis, numbness, pain, and, in extreme cases, gangrene.
reperfusion injury—Refers to myocar-dial, vascular, or electro-physiological dysfunction that is induced by the restoration of blood flow to previously ischemic tissue.
restenosis—A condition where an artery plugs up again following treatment to open it up.
stent—A metal device that is used to hold tissue in place. For example, a stent can keep blood vessels open after a sur-gical procedure or heart catheterization.
stroke—Usually caused by atheroscle-rosis. It results in death or serious brain damage, such as paralysis or loss of speech. An ischemic stroke is caused by blocked or narrowed arteries that prevent sufficient blood and oxygen from reaching the brain.
thromboembolism—Blockage of a blood vessel by a fragment that has broken off and been carried from a thrombus (blood clot) elsewhere in the circulation.
thrombosis—The formation of a blood clot within the heart or a blood vessel.
the drug discovery, development and approval process
The U.S. system of new drug approvals is perhaps the most rigorous in the world.
It takes 10-15 years, on average, for an experi-mental drug to travel from lab to U.S. patients, according to the Tufts Center for the Study of Drug Development. Only five in 5,000 com-pounds that enter preclinical testing make it to human testing. And only one of those five is approved for sale.
On average, it costs a company $1.2 billion, including the cost of failures, to get one new medicine from the laboratory to U.S. patients, according to a recent study by the Tufts Center for the Study of Drug Development.
Once a new compound has been identified in the laboratory, medicines are usually developed as follows:
Preclinical Testing. A pharmaceutical company conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the compound is evalu-ated for safety.
Investigational New Drug Application (IND). After completing preclinical testing, a com-pany files an IND with the U.S. Food and Drug Administration (FDA) to begin to test the drug
in people. The IND shows results of previous experiments; how, where and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in the animal studies; and how the compound is manufac-tured. All clinical trials must be reviewed and ap-proved by the Institutional Review Board (IRB) where the trials will be conducted. Progress reports on clinical trials must be submitted at least annually to FDA and the IRB.
Clinical Trials, Phase I—Researchers test the drug in a small group of people, usually between 20 and 80 healthy adult volunteers, to evaluate its initial safety and tolerability profile, deter-mine a safe dosage range, and identify potential side effects.
Clinical Trials, Phase II—The drug is given to volunteer patients, usually between 100 and 300, to see if it is effective, identify an optimal dose, and to further evaluate its short-term safety.
Clinical Trials, Phase III—The drug is given to a larger, more diverse patient population, often involving between 1,000 and 3,000 patients (but sometime many more thousands), to gener-
ate statistically significant evidence to confirm its safety and effectiveness. They are the lon-gest studies, and usually take place in multiple sites around the world.
New Drug Application (NDA)/Biologic License Application (BLA). Following the completion of all three phases of clinical trials, a company analyzes all of the data and files an NDA or BLA with FDA if the data successfully demonstrate both safety and effectiveness. The applications contain all of the scientific information that the company has gathered. Applications typically run 100,000 pages or more.
Approval. Once FDA approves an NDA or BLA, the new medicine becomes available for physi-cians to prescribe. A company must continue to submit periodic reports to FDA, including any cases of adverse reactions and appropriate quality-control records. For some medicines, FDA requires additional trials (Phase IV) to evaluate long-term effects.
Discovering and developing safe and effective new medicines is a long, difficult, and expensive process. PhRMA member companies invested an estimated $48.5 billion in research and develop-ment in 2012.
Developing a new medicine takes an average of 10-15 years; For every 5,000-10,000 compounds in the pipeline, only 1 is approved.
The Drug Development and Approval process
PRE-
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DRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG
3 – 6 Y E A RS 6 – 7 Y E A RS 0. 5 – 2 Y E A RS
100 – 300 1,000 – 3,00020 –80
PHASE 2
PHASE 3
PHASE 1
IND
SU
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PHA
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: PO
ST-M
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NUMBER OF VOLUNTEERS
ONE FDA-APPROVED
DRUG
5,000 – 10,000
COMPOUNDS
250 5
Drug Discovery and Development: A LONG, RISKY ROAD
