2012年在研哮喘药物

Biopharmaceutical Research Companies Are Studying More Than 70 Medicines for Asthma Medicines in Development AsthmA presented by america’s biopharmaceutical research companies 2012 RepoRt 114 91 127 127 138 131 109 107 20 09 20 01 20 05 19 97 Children (0 – 17) Adults (18+) Asthma Prevalence in the United States (Rate per 1,000) Source: U.S. Centers for Disease Control and Prevention, National Center for Health Statistics. 24 million American adults and children suffer from asthma; each day 40,000 Americans miss school or work due to asthma More than 24 million Americans are affected by asthma, with prevalence increasing 12 percent in the last decade. Asthma is a nar- rowing of the airways to the lungs caused by inflammation in the air passages resulting from both genetic and environmental influences. It is the most common chronic condition in children and costs the U.S. economy an estimated $56 billion each year in direct and indirect costs. America’s biopharmaceutical research com- panies are developing 74 medicines to treat or prevent asthma. All of the medicines are either in clinical trials or awaiting review by the U.S. Food and Drug Administration. New medicines today in the pipeline offer hope of reducing the human and economic costs of asthma. Examples of some medicines now being tested to treat the disease include: • A monoclonal antibody that inhibits eosinophils from accumulating in the lungs. • A new inhalation therapy that harnesses the body’s natural defenses in the airway against asthma. • A medicine that blocks the pro-inflam- matory effect of prostaglandin in allergic asthma. 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 tool at their disposal. Advances in our understanding of diseases and how to treat them have allowed America’s biopharmaceutical research companies to conduct the cutting-edge research needed to reduce the destructive toll of asthma. Medicines in Development Asthma 20122 Medicines in Development for Asthma * For more information about a specific medicine in this report, please call the telephone number listed. AsthmA product Name Sponsor Indication Development Status* ABT-308 (IL-13 modulator) Abbott Laboratories Abbott Park, IL asthma Phase I (847) 937-6100 AM211 (CRTH2 antagonist) Panmira Pharmaceuticals San Diego, CA asthma Phase I completed (858) 875-4810 AMG 157 (mAb) Amgen Thousand Oaks, CA asthma Phase I (800) 772-6436 AMG 761 (mAb) Amgen Thousand Oaks, CA asthma Phase I (800) 772-6436 AMG 827 (brodalumab) Amgen Thousand Oaks, CA asthma Phase II (800) 772-6436 AMG 853 (CRTH2/D-prostanoid receptor) Amgen Thousand Oaks, CA asthma Phase III (800) 772-6436 Arcapta® Neohaler® indacaterol Novartis Pharmaceuticals East Hanover, NJ asthma Phase III (888) 669-6682 ARRY-502 (CRTH2 antagonist) Array BioPharma Boulder, CO allergic asthma Phase I (877) 633-2436 ASM8 Pharmaxis Exton, PA allergic asthma Phase II (610) 363-5120 AZD1981 AstraZeneca Wilmington, DE asthma Phase II (800) 236-9933 benralizumab (MEDI-563) MedImmune Gaithersburg, MD asthma Phase II (301) 398-0000 BI-54903 Boehringer Ingelheim Pharmaceuticals Ridgefield, CT asthma Phase II (800) 243-0127 BI-54903/olodaterol fixed-dose combination Boehringer Ingelheim Pharmaceuticals Ridgefield, CT asthma Phase II (800) 243-0127 BI-144807 Boehringer Ingelheim Pharmaceuticals Ridgefield, CT asthma Phase I (800) 243-0127 Medicines in Development Asthma 2012 3 Medicines in Development for Asthma AsthmA product Name Sponsor Indication Development Status BI-671800 Boehringer Ingelheim Pharmaceuticals Ridgefield, CT asthma Phase II (800) 243-0127 Bosatria™ mepolizumab GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II (888) 825-5249 CNTO 3157 (mAb) Janssen Biotech Horsham, PA asthma Phase I (800) 526-7736 CNTO 5825 (mAb) Janssen Biotech Horsham, PA allergic asthma Phase I (800) 526-7736 Dulera® mometasone furoate/ formoterol fumarate Merck Whitehouse Station, NJ asthma (children under 12 years) -------------------------------------------------- allergic asthma (adults and adolescents) Phase III (800) 672-6372 ------------------------------------------- Phase II (800) 672-6372 E004 (epinephrine inhalation aerosol) Amphastar Pharmaceuticals Rancho Cucamonga, CA asthma Phase III (800) 423-4136 fluticasone furoate/ fluticasone propionate GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase III (888) 825-5249 Flutiform™ formoterol/fluticasone propionate SkyePharma London, England asthma application submitted www.skyepharma.com GSK1440115 GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase I completed (888) 825-5249 GSK2190914 GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II (888) 825-5249 GSK2190915 (fiboflapon) GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II (888) 825-5249 GSK2239633 (CCR4 receptor antagonist) GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase I (888) 825-5249 GSK2269557 GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase I (888) 825-5249 GSK256066 (PDE-IV inhibitor) GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II (888) 825-5249 Medicines in Development Asthma 20124 Medicines in Development for Asthma AsthmA product Name Sponsor Indication Development Status GSK679586 (mAb) GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II completed (888) 825-5249 GSK870086 (glucocortoid agonist) GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II (888) 825-5249 GW766994 (CCR3 antagonist) GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase II (888) 825-5249 house dust mite allergy vaccine tablet (MK-8237) ALK-Abello Horsholm, Denmark Merck Whitehouse Station, NJ allergic asthma Phase II (800) 672-6372 ibudilast (MN-166) MediciNova San Diego, CA asthma Phase II (858) 373-1500 IMO-2134 Idera Pharmaceuticals Cambridge, MA asthma Phase I (617) 679-5500 indacaterol/mometasone (QMF149 Twisthaler®) Novartis Pharmaceuticals East Hanover, NJ asthma Phase II (888) 669-6682 INV102 (oral nadolol) Inverseon San Francisco, CA asthma Phase II www.inverseon.com JNJ-39758979 Janssen Research & Development Raritan, NJ asthma Phase II completed (800) 526-7736 JNJ-40929837 Janssen Research & Development Raritan, NJ asthma Phase II (800) 526-7736 LAS 100977 (LABA) Almirall Barcelona, Spain Forest Laboratories New York, NY asthma Phase II (800) 678-1605 lebrikizumab (RG3637) Genentech South San Francisco, CA allergic asthma, asthma Phase II (800) 626-3553 masitinib AB Science Short Hills, NJ asthma Phase III (973) 218-2437 MK-1029 Merck Whitehouse Station, NJ mild to moderate asthma Phase I (800) 672-6372 Medicines in Development Asthma 2012 5 Medicines in Development for Asthma AsthmA product Name Sponsor Indication Development Status MN-221 MediciNova San Diego, CA exacerbations of acute asthma Phase II (858) 373-1500 montelukast/mometasone (MK-0476C) Merck Whitehouse Station, NJ asthma Phase II (800) 672-6372 N6022 N30 Pharma Boulder, CO acute asthma Phase I/II (920) 945-7700 olodaterol (BI-1744) Boehringer Ingelheim Pharmaceuticals Ridgefield, CT asthma Phase II (800) 243-0127 ONO-6950 Ono Pharma USA Trenton, NJ asthma Phase I (609) 219-1010 OPK-0018 OPKO Health Miami, FL asthma Phase I (305) 575-4100 PUR003 (liquid iCALM) Pulmatrix Lexington, MA asthma Phase I (781) 357-2333 QAV680 Novartis Pharmaceuticals East Hanover, NJ asthma Phase II (888) 669-6682 QAW039 Novartis Pharmaceuticals East Hanover, NJ asthma Phase II (888) 669-6682 QAX576 Novartis Pharmaceuticals East Hanover, NJ asthma Phase II (888) 669-6682 QGE031 Novartis Pharmaceuticals East Hanover, NJ asthma Phase I (888) 669-6682 R343 Rigel Pharmaceuticals South San Francisco, CA allergic asthma Phase I completed (650) 624-1100 R(+) zileuton Cornerstone Therapeutics Cary, NC asthma Phase I (888) 466-6505 Relovair™ vinanterol inhalation/ fluticasone furoate powder GlaxoSmithKline Rsch. Triangle Park, NC Theravance South San Francisco, CA asthma -------------------------------------------------- asthma (children 5 – 11 years) Phase III (888) 825-5249 (877) 275-8479 ------------------------------------------- Phase II (888) 825-5249 (877) 275-8479 Medicines in Development Asthma 20126 AsthmA product Name Sponsor Indication Development Status reslizumab Cephalon Frazer, PA eosinophilic asthma Phase III (610) 344-0200 RG7185 (CRTH2-antagonist) Genentech South San Francisco, CA asthma Phase I (800) 626-3553 RG7449 (anti-M1 prime mAb) Genentech South San Francisco, CA allergic asthma Phase II (800) 626-3553 RNS60 Revalesio Tacoma, WA asthma Phase II www.revalesio.com RX-10001 Resolvyx Pharmaceuticals Cambridge, MA asthma Phase I (781) 541-5045 salbutamol dry-powder inhalation Teva North America North Wales, PA asthma Phase III (888) 838-2872 SAR231893 (REGN668) Regeneron Pharmaceuticals Tarrytown, NY sanofi-aventis Bridgewater, NJ asthma Phase II (914) 345-7400 (800) 981-2491 setipiprant (ACT-129968) Actelion Pharmaceuticals South San Francisco, CA asthma Phase II (650) 624-6900 Singulair® montelukast Merck Whitehouse Station, NJ exercise-induced asthma (children 4-14 years) Phase III completed (800) 672-6372 Syk kinase silencer (Excellair™) ZaBeCor Pharmaceuticals Bala Cynwyd, PA asthma Phase II (610) 660-7733 Spiriva® HandiHaler® tiotropium bromide Boehringer Ingelheim Pharmaceuticals Ridgefield, CT Pfizer New York, NY moderate to severe asthma Phase III (800) 243-0127 (860) 732-5156 Symbicort® formoterol/budesonide inhalation AstraZeneca Wilmington, DE asthma (children 6-11 years) Phase III (800) 236-9933 Symbicort® SMARt® formoterol/budesonide AstraZeneca Wilmington, DE asthma Phase III (800) 236-9933 TC-6987 Targacept Winston-Salem, NC asthma Phase II (336) 480-2100 Medicines in Development for Asthma Medicines in Development Asthma 2012 7 AsthmA product Name Sponsor Indication Development Status tralokinumab (CAT-354) MedImmune Gaithersburg, MD asthma Phase II (301) 398-0000 Veramyst® fluticasone furoate GlaxoSmithKline Rsch. Triangle Park, NC asthma -------------------------------------------------- asthma (in children 5 – 11 years) Phase III (888) 825-5249 ------------------------------------------- Phase II (888) 825-5249 vilanterol GlaxoSmithKline Rsch. Triangle Park, NC asthma Phase III (888) 825-5249 VR506 Vectura Wiltshire, United Kingdom asthma Phase II/III www.vectura.com 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 February 3, 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 Asthma 20128 Glossary application submitted—Application for marketing has been submitted to the Food and Drug Administration (FDA). asthma—A disorder that causes the airways of the lungs to swell and narrow, leading to wheezing, shortness of breath, chest tightness, and coughing. Asthma is caused by inflamma- tion in the airways. An asthma attack occurs when the muscles surrounding the airways become tight and the lining of the air passages swells, thus reducing the amount of air that can pass through. Most people with asthma have attacks separated by symptom-free periods Some people have long-term shortness of breath with episodes of increased shortness of breath. Either wheezing or a cough may be the main symptom. Asthma attacks can last for minutes to days, and can become dangerous if the airflow is severely restricted. In sensitive people, asthma symptoms can be triggered by breathing in allergy-causing substances (called allergens or triggers). Some common asthma triggers include pet hair or dander, dust, changes in the weather, chemicals in the air or in food, mold, pollen, and tobacco smoke. eosinophilic asthma—Eosinophils are a type of white blood cell that tends to increase with worsening asthma and other allergic condi- tions. Eosinophils normally help protect the body from foreign invaders such as bacteria, viruses, and parasites, but in asthma eosino- phils release chemicals that lead to inflam- mation. Eosinophils are produced in the bone marrow, but travel to other organs in the body when exposed to an asthma trigger. Re- exposure to a trigger (an allergen) leads to the release of chemicals like histamine that cause bronchoconstriction and asthma symptoms such as wheezing, chest tightness, shortness of breath, and chronic cough. 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. Medicines in Development Asthma 2012 9 Selected Facts about Asthma in the United States* • Approximately 24.6 million Americans (including 7.1 million children) had asthma in 2009. That was a rate of 81.5 per 1,000 population. The highest prevalence rate was seen in those 5-17 years of age (109.3 per 1,000 population). Overall, the rate in those under 18 (96.1 per 1,000) was significantly greater than those over 18 (76.8 per 1,000). • In 2009, an estimated 12.8 million Americans (including 4.1 million children under 18) had an asthma attack. That represents 48 percent of the 24.6 million people who currently have asthma. The asthma attack rate was 42.6 per 1,000 population. • The overall percentage of asthma sufferers tends to be highest in the South, in non-Hispanic whites, in 18-44 year olds, and in females. • The hospital discharge rate for asthma increased dramatically from 1979 to 1988, remained stable in the early 1990s, and peaked at 511,000 discharges (19.5 per 10,000 population) in 1995. During 2006, 444,000 discharges (14.9 per 10,000 population) were attributed to asthma. Between 2003 and 2006, there was a 25 percent decrease in the hospitalization discharge rate for asthma in the United States. • In 2006, asthma caused 10.6 million physician office visits, 1.2 million hospital outpatient department visits, and almost 1.7 million emer- gency room visits. • In 2008, asthma accounted for an estimated 14.4 million lost school days for children and 14.2 million lost work days for adults. • In 2007, 3,447 people died of asthma. The number of asthma deaths has decreased by 26 percent since 1999. • From 2002 to 2007, the annual economic cost of asthma in the United States was $56 billion; direct health care costs consisted of $50.1 billion with indirect costs (lost productivity) contributing an additional $5.9 billion. • Females traditionally have consistently higher rates of asthma than males. In 2009, females were about 11.1 percent more likely than males to ever have been diagnosed with asthma. • In 2009, 10.3 million males and 14.2 million females had asthma. The overall prevalence rate in females (92.7 per 1,000 people) was 33 percent greater than the rate in males (69.9 per 1,000 people). Among adults over 18 years, females were 76 percent more likely than males to have asthma (97.0 per 1,000 vs. 55.1 per 1,000). However, this pattern is reversed among children. The current asthma prevalence rate for boys under 18 (112.8 per 1,000) was 44 percent higher than the rate among girls (78.6 per 1,000). The difference in rates between sexes is statistically significant in both children and adults. • Females tend to have consistently higher asthma attack prevalence rates than males. In 2009, 7.6 million females (49.6 per 1,000) had an asthma attack compared to 5.2 million males (35.2 per 1,000). The difference in attack prevalence rates between sexes has been significant each year since 1999. • Between 1995 and 2006, the number of hospital discharges due to asthma decreased 13 percent overall, 16 percent in males, and 12 per- cent in females. In 2006, a total of 266,000 discharges were reported in females and 177,000 were reported in males. • In 2007, the age-adjusted death rate for asthma was 1.1 per 100,000 population. That year, the female age-adjusted death rate was 33 per- cent greater than the rate seen in males. Of the 3,447 people who died of asthma in 2007, approximately 63 percent of them were women. overview Asthma in Females and Males Medicines in Development Asthma 201210 Selected Facts about Asthma in the United States* • Since 1999, children ages 5-17 have had the highest asthma prevalence. In 2009, 8.5 million children ages 5-17 had been diagnosed with asthma in their lifetime. • For the past 10 years, 5- to 17-year-olds had the highest asthma attack prevalence rates while those over 65 had the lowest every year until 2009, when those 18-44 had the highest rates. Since 1999, the asthma attack prevalence rate in those under age 18 has been significantly greater than among those over 18; in 2009, those rates were 54.8 versus 28.8 per 1,000, respectively. • Hospital discharges due to asthma are very common among the pediatric population. Approximately 33 percent of the asthma discharges in 2006 were in those under age 15, although only 20.2 percent of the U.S. population was under age 15. • Asthma deaths are rare among children and increase with age. In 2007, 152 children under age 15 died from asthma (0.2 per 100,000 popula- tion) compared to 659 adults over 85. (The death rate in those 85 and over was 173 percent greater than the second highest mortality rate, seen among those 75-84 years of age [12.0 per 100,000 versus 4.4 per 100,000]). • African Americans are more likely to be diagnosed with asthma over their lifetime. In 2009, the current asthma prevalence was 43 percent higher in blacks than in whites (111.5 per 1,000 people versus 78 per 1,000 people, respectively). The difference between races is statistically significant. The highest prevalence for whites and blacks were among the 5-17 age group. Whites under age 5 and blacks age 65 and older had the lowest prevalence rates compared to other age groups within each race. • In 2009, the asthma attack prevalence in blacks was 40 percent higher than in whites. The asthma attack prevalence in whites and blacks were highest among the 5-17 age group and lowest in those 65 years and older. • The 2006 hospital discharge rate for African Americans with asthma (29.3 per 10,000 people) was more than 3 times higher than that seen in whites and 4.4 times higher than that seen in other races (9.6 and 6.7 per 10,000, respectively). • In 2007, the age-adjusted death rate for asthma was 2.8 times higher among the black population than among the white population (2.5 versus 0.9 per 100,000, respectively). Black women had the highest age-adjusted mortality rate due to asthma (2.2 per 100,000). • In 2009, 5.3 million Hispanics had been diagnosed with asthma in their lifetime; 3 million reported that they still have the disease; and 1.6 mil- lion of those