2012年在研慢性阻塞性肺病药物

Today, more than 13 million American adults are suffering from chronic obstructive pulmonary dis- ease (COPD), leading to limitations in their ability to work, exercise and perform normal social activ- ity. COPD, a chronic lower respiratory disease that includes chronic bronchitis and emphysema, is characterized by obstruction of airflow to the lungs that interferes with normal breathing. America’s biopharmaceutical research compa- nies have 54 medicines for treating COPD in the later stages of the pipeline, meaning they are either in clinical trials or awaiting FDA review. Each year, more than 120,000 Americans die from the disease. In addition to robbing millions of patients of their ability to breathe normally, COPD costs the nation approximately $49.9 billion, including direct healthcare costs and other indirect costs, according to the National Institutes of Health. While smoking is the main risk factor for COPD, and nearly 90 percent of COPD deaths are caused by smoking, other causes include air pollution, second-hand smoke, occupational dusts and chemicals, hereditary and childhood respiratory infections. America’s biopharmaceutical researchers are exploring various new ways to attack this devas- tating disease. Examples of new approaches to treating COPD include: • An adult stem cell therapy that targets a protein in the blood that is often elevated in COPD. • A monoclonal antibody that acts on IL-1 receptors involved in inflammatory conditions. • A medicine that targets the underlying inflammation in COPD. The quest for new medicines is intense and financially risky. Each new medicine costs, on average, more than $1 billion and takes 10 to 15 years to develop. But new scientific advances are increasing our knowledge, and researchers are using every cutting-edge tool at their disposal to find new treatments and potential cures. More Than 50 Medicines in Pipeline for Third Leading Cause of Death in the United States Medicines in Development COPD presented by america’s biopharmaceutical research companies 2012 RepoRt 7.1 9.8 10.5 13.1 20 08 19 90 20 00 19 80 COPD Prevalence in the United States (in millions) Source: U.S. Centers for Disease Control and Prevention COPD affects more than 13 million American adults; more than 120,000 die from the disease each year Medicines in Development COPD 20122 Medicines in Development for COPD * For more information about a specific medicine in this report, please call the telephone number listed. ChrOniC ObstruCtive PulmOnary Disease (COPD) product Name Sponsor Indication Development Status* aclidinium inhalation Almirall Barcelona, Spain Forest Laboratories New York, NY chronic obstructive pulmonary disease (COPD) application submitted (800) 678-1605 aclidinium/formoterol inhalation Almirall Barcelona, Spain Forest Laboratories New York, NY COPD Phase III (800) 678-1605 AM211 Panmira Pharmaceuticals San Diego, CA COPD Phase I (858) 875-4810 AZD1981 (CRTh2 receptor antagonist) AstraZeneca Wilmington, DE COPD Phase II (800) 236-9933 AZD 2115 (MABA) AstraZeneca Wilmington, DE COPD Phase I (800) 236-9933 AZD2423 (CCR2b antagonist) AstraZeneca Wilmington, DE COPD Phase II (800) 236-9933 AZD3199 (iLABA) AstraZeneca Wilmington, DE COPD Phase II (800) 236-9933 AZD5069 (CXCR2) AstraZeneca Wilmington, DE COPD Phase II (800) 236-9933 AZD5423 (inhaled SEGRA) AstraZeneca Wilmington, DE COPD Phase II (800) 236-9933 AZD8683 (muscarinic antagonist) AstraZeneca Wilmington, DE COPD Phase I (800) 236-9933 BCT197 Novartis Pharmaceuticals East Hanover, NJ COPD Phase II (888) 669-6682 BI-137882 Boehringer Ingelheim Pharmaceuticals Ridgefield, CT COPD Phase I (800) 243-0127 BIO-11006 BioMarck Pharmaceuticals Durham, NC COPD Phase II www.biomarck.com Dulera® mometasone/formoterol Merck Whitehouse Station, NJ COPD application submitted (800) 672-6372 Medicines in Development COPD 2012 3 Medicines in Development for COPD ChrOniC ObstruCtive PulmOnary Disease (COPD) product Name Sponsor Indication Development Status* EP-101 (LAMA) Elevation Pharmaceuticals San Diego, CA COPD Phase II (858) 436-1616 EP-102 (LAMA/LABA) Elevation Pharmaceuticals San Diego, CA COPD Phase II (858) 436-1616 EPI-12323 EpiGenesis Pharmaceuticals Cranbury, NJ COPD Phase II (609) 409-6080 formoterol/fluticasone fixed-dose combination (inhalation) Dey Pharma Basking Ridge, NJ COPD Phase II (908) 542-1999 GSK256066 (inhaled PDE4 inhibitor) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase II (888) 825-5249 GSK573719 (muscarinic acetylcholine antagonist) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase III (888) 825-5249 GSK573719/vilanterol (muscarinic acetylcholine antagonist/long-acting beta2 agonist) GlaxoSmithKline Rsch. Triangle Park, NC Theravance South San Francisco, CA COPD Phase III (888) 825-5249 (877) 275-8479 GSK610677 (inhaled p38 kinase inhibitor) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase I (888) 825-5249 GSK961081 (muscarinic antagonist/ beta2 agonist) GlaxoSmithKline Rsch. Triangle Park, NC Theravance South San Francisco, CA COPD Phase II (888) 825-5249 (877) 275-8479 GSK1325756 (chemokine receptor antagonist-2) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase I (888) 825-5249 GSK2245840 (SIRT1 activator) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase I (888) 825-5249 Ilaris® canakinumab Novartis Pharmaceuticals East Hanover, NJ COPD Phase I/II completed (888) 669-6682 LAS 100977 (LABA) Almirall Barcelona, Spain Forest Laboratories New York, NY COPD Phase II (800) 678-1605 levosalbutamol/ipratropium inhalation solution Sunovion Pharmaceuticals Marlborough, MA COPD Phase II (508) 481-6700 Medicines in Development COPD 20124 Medicines in Development for COPD ChrOniC ObstruCtive PulmOnary Disease (COPD) product Name Sponsor Indication Development Status* losmapimod (oral p38 kinase inhibitor) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase II (888) 825-5249 MEDI-2338 (anti-IL-18 mAb) MedImmune Gaithersburg, MD COPD Phase I (301) 398-0000 MEDI-8968 (anti-IL-1R) MedImmune Gaithersburg, MD COPD Phase I (301) 398-0000 MK-7123 (navarixin) Ligand Pharmaceuticals La Jolla, CA Merck Whitehouse Station, NJ COPD Phase II (858) 550-7500 (800) 672-6372 MN-166 (ibudilast) MediciNova San Diego, CA COPD Phase I completed (858) 373-1500 MN-221 (bedoradrine) MediciNova San Diego, CA COPD Phase I (858) 373-1500 NVA237 (glycopyrrolate inhalation) Novartis Pharmaceuticals East Hanover, NJ COPD Phase III (888) 669-6682 O-desulfated heparin intravenous ParinGenix Tucson, AZ COPD Phase II (617) 480-5068 olodaterol Boehringer Ingelheim Pharmaceuticals Ridgefield, CT COPD Phase III (800) 243-0127 olodaterol/tiotropium bromide Boehringer Ingelheim Pharmaceuticals Ridgefield, CT COPD Phase II (800) 243-0127 paclitaxel-loaded stent Broncus Technologies Mountain View, CA emphysema Phase III (650) 428-1600 PF-03715455 Pfizer New York, NY COPD Phase I (860) 732-5156 PH-797804 Pfizer New York, NY COPD Phase II (860) 732-5156 prochymal® remestemcel-L Osiris Therapeutics Columbia, MD COPD Phase II (443) 545-1800 Medicines in Development COPD 2012 5 Medicines in Development for COPD ChrOniC ObstruCtive PulmOnary Disease (COPD) product Name Sponsor Indication Development Status* PT001 (glycopyrrolate inhalation aerosol) Pearl Therapeutics Redwood City, CA COPD Phase II (650) 305-2600 PT003 (glycopyrrolate/formoterol inhalation aerosol) Pearl Therapeutics Redwood City, CA COPD Phase II (650) 305-2600 PT005 (formoterol inhalation aerosol) Pearl Therapeutics Redwood City, CA COPD Phase II (650) 305-2600 PUR118 Pulmatrix Lexington, MA COPD Phase I (781) 357-2333 QMF149 (indacaterol/mometasone) Novartis Pharmaceuticals East Hanover, NJ COPD Phase II (888) 669-6682 QVA149 (glycopyrrolate/indacaterol inhalation) Novartis Pharmaceuticals East Hanover, NJ COPD Phase III (888) 669-6682 Relovair™ vilanterol/fluticasone furoate GlaxoSmithKline Rsch. Triangle Park, NC Theravance South San Francisco, CA COPD Phase III (888) 825-5249 (877) 275-8479 RV568 RespiVert London, England Janssen Research & Development Raritan, NJ COPD Phase II (800) 526-7736 TD-4208 (LAMA) Theravance South San Francisco, CA COPD Phase II (877) 275-8479 tetomilast Otsuka America Pharmaceutical Rockville, MD COPD Phase II (800) 562-3974 vilanterol (long-acting beta2 agonist) GlaxoSmithKline Rsch. Triangle Park, NC COPD Phase III (888) 825-5249 Veldona® interferon-alpha Amarillo Biosciences Amarillo, TX COPD (chronic coughing) Phase II www.amarbio.com Medicines in Development COPD 20126 Glossary application submitted—Application for marketing has been submitted to the Food and Drug Administration (FDA). chronic obstructive pulmonary disease (CopD)—A group of lung diseases, icluding chronic bronchitis and emphysema, in which there is a persistent disruption of airflow out of the lungs and eventual hypoxemia (low level of oxygen in the blood). emphysema—An enlargement of the tiny air sacs of the lungs (alveoli) and the destruction of their walls, which causes structural and permanent reduction of airflow. phase I—Safety testing and pharmacological profiling in humans. phase II—Effectiveness and safety testing in humans. phase III—Extensive clinical trials to demon- strate safety and efficacy in humans. The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” database based on the latest information. Report current as of January 12, 2012. 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 web site. A publication of phRMA’s Communications & public Affairs Department. (202) 835-3460 www.phrma.org | www.innovation.org | www.pparx.org | www.buysafedrugs.info Provided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2012 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given. Pharmaceutical Research and Manufacturers of America • 950 F Street, NW, Washington, DC 20004 Medicines in Development COPD 2012 7 Selected Facts about COPD • Chronic obstructive pulmonary disease (CopD) is an umbrella term for progressive lung diseases, including chronic bronchitis and emphysema, that are characterized by obstruction to airflow that interferes with normal breathing. In 2008, 13.1 million U.S. adults (ages 18 and over) were estimated to have COPD. However, close to 24 million U.S. adults have evidence of impaired lung function, indicating an under diagnosis of COPD.1 • In 2008, an estimated 9.8 million Americans reported a physician diagnosis of chronic bronchitis, the inflammation and eventual scarring of the lining of the bronchial tubes. Chronic bronchitis affects people of all ages, although people age 65 and older have the highest rate at 56.3 per 1,000 population.1 • Females are about twice as likely to be diagnosed with chronic bronchitis as males. In 2008, 3.1 million males had a diagnosis of chronic bronchitis compared with 6.7 million females.1 • Years of exposure to the irritation of cigarette smoke usually precede the development of emphysema, which irreversibly damages the air sacs of the lungs and results in permanent “holes” in the tissues of the lower lungs. Of the estimated 3.7 million Americans diagnosed with emphysema, 94 percent are 45 or older.1 • Historically, men have been more likely than women to receive a diagnosis of emphysema. However, in 2008 more women (more than 2 million) reported a diagnosis of emphysema than men (almost 1.8 million).1 • Smoking is the primary risk factor for CopD. Approximately 85 percent to 90 percent of COPD deaths are caused by smoking. Female smokers are nearly 13 times as likely to die from COPD as women who have never smoked. Male smokers are nearly 12 times as likely to die from COPD as men who have never smoked.1 • CopD is the third leading cause of death in America, claiming the lives of 137,693 Americans in 2008. That was the ninth consecutive year in which women exceeded men in the number of deaths attributable to COPD. In 2008, more than 71,000 females died compared to nearly 66,000 males.2 • An American Lung Association survey revealed that half of all CopD patients (51 percent) say their condition limits their ability to work. It also limits them in normal physical exertion (70 percent), household chores (56 percent), social activities (53 percent), sleeping (50 percent), and family activities (46 percent).1 • In 2010, the cost to the nation for CopD was estimated to be approximately $49.9 billion, including $29.5 billion in direct health care expen- ditures, $8.0 billion in indirect morbidity costs, and $12.4 billion in indirect mortality costs.1 Selected Facts about Chronic obstructive pulmonary Disease (CopD) in the United States Sources: 1. American Lung Association, www.lungusa.org 2. U.S. Centers for Disease Control and Prevention, www.cdc.gov 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 experimental 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 compounds 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 2007 study by the Tufts Center for the Study of Drug Development. Once a new compound has been identified in the laboratory, medicines are usually devel- oped as follows: preclinical testing. A pharmaceutical com- pany conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the com- pound is evaluated for safety. Investigational New Drug Application (IND). After completing preclinical testing, a company 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 manufactured. All clinical trials must be reviewed and approved 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. These tests usually involve about 20 to 100 healthy volunteers. The tests study a drug’s safety profile, including the safe dosage range. The studies also determine how a drug is absorbed, distributed, metabo- lized, and excreted as well as the duration of its action. Clinical trials, phase II. In this phase, controlled trials of approximately 100 to 500 volunteer patients (people with the disease) assess a drug’s effectiveness and determine the early side effect profile. Clinical trials, phase III. This phase usually involves 1,000 to 5,000 patients in clinics and hospitals. Physicians monitor patients closely to confirm efficacy and identify adverse events. 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 physicians 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. Biopharmaceutical companies invested an estimated $67.4 billion in research and development in 2010. The Drug Discovery, Development and Approval Process It takes 10-15 years on average for an experimental drug to travel from the lab to U.S. patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved. The Drug Development and Approval Process