COPD Presented by America’S Biopharmaceutical Research Companies

2012 Repo r t

Medicines in Development COPD presented by america’s biopharmaceutical research companies

More Than 50 Medicines in Pipeline for Third Leading Cause of Death in the United States

COPD Prevalence in the COPD affects United States more than 13 million (in millions) American adults; 13.1 more than 120,000 die from the disease each year

10.5

9.8 Today, more than 13 million American adults are America’s biopharmaceutical researchers are suffering from chronic obstructive pulmonary dis- exploring various new ways to attack this devas- ease (COPD), leading to limitations in their ability tating disease. Examples of new approaches to to work, exercise and perform normal social activ- treating COPD include: ity. COPD, a chronic lower respiratory disease • An adult stem cell therapy that targets a that includes chronic bronchitis and emphysema, protein in the blood that is often elevated 7.1 is characterized by obstruction of airflow to the in COPD. lungs that interferes with normal breathing. • A monoclonal antibody that acts on America’s biopharmaceutical research compa- IL-1 receptors involved in inflammatory nies have 54 medicines for treating COPD in the conditions. later stages of the pipeline, meaning they are either in clinical trials or awaiting FDA review. • A medicine that targets the underlying inflammation in COPD. Each year, more than 120,000 Americans die from the disease. In addition to robbing The quest for new medicines is intense and millions of patients of their ability to breathe financially risky. Each new medicine costs, normally, COPD costs the nation approximately on average, more than $1 billion and takes $49.9 billion, including direct healthcare costs 10 to 15 years to develop. But new scientific and other indirect costs, according to the advances are increasing our knowledge, and National Institutes of Health. researchers are using every cutting-edge tool While smoking is the main risk factor for COPD, at their disposal to find new treatments and and nearly 90 percent of COPD deaths are potential cures. 1980 1990 2000 2008 caused by smoking, other causes include air pollution, second-hand smoke, occupational Source: U.S. Centers for Disease dusts and chemicals, hereditary and childhood Control and Prevention respiratory infections. Medicines in Development for COPD

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Status*

aclidinium Almirall chronic obstructive pulmonary application submitted inhalation Barcelona, Spain disease (COPD) (800) 678-1605 Forest Laboratories New York, NY

aclidinium/formoterol Almirall COPD Phase III inhalation Barcelona, Spain (800) 678-1605 Forest Laboratories New York, NY

AM211 Panmira Pharmaceuticals COPD Phase I San Diego, CA (858) 875-4810

AZD1981 AstraZeneca COPD Phase II (CRTh2 receptor antagonist) Wilmington, DE (800) 236-9933

AZD 2115 AstraZeneca COPD Phase I (MABA) Wilmington, DE (800) 236-9933

AZD2423 AstraZeneca COPD Phase II (CCR2b antagonist) Wilmington, DE (800) 236-9933

AZD3199 AstraZeneca COPD Phase II (iLABA) Wilmington, DE (800) 236-9933

AZD5069 AstraZeneca COPD Phase II (CXCR2) Wilmington, DE (800) 236-9933

AZD5423 AstraZeneca COPD Phase II (inhaled SEGRA) Wilmington, DE (800) 236-9933

AZD8683 AstraZeneca COPD Phase I (muscarinic antagonist) Wilmington, DE (800) 236-9933

BCT197 Novartis Pharmaceuticals COPD Phase II East Hanover, NJ (888) 669-6682

BI-137882 Boehringer Ingelheim COPD Phase I Pharmaceuticals (800) 243-0127 Ridgefield, CT

BIO-11006 BioMarck Pharmaceuticals COPD Phase II Durham, NC www.biomarck.com

Dulera® Merck COPD application submitted mometasone/formoterol Whitehouse Station, NJ (800) 672-6372

* For more information about a specific medicine in this report, please call the telephone number listed.

2 Medicines in Development COPD 2012 Medicines in Development for COPD

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Status*

EP-101 Elevation Pharmaceuticals COPD Phase II (LAMA) San Diego, CA (858) 436-1616

EP-102 Elevation Pharmaceuticals COPD Phase II (LAMA/LABA) San Diego, CA (858) 436-1616

EPI-12323 EpiGenesis Pharmaceuticals COPD Phase II Cranbury, NJ (609) 409-6080

formoterol/fluticasone Dey Pharma COPD Phase II fixed-dose combination Basking Ridge, NJ (908) 542-1999 (inhalation)

GSK256066 GlaxoSmithKline COPD Phase II (inhaled PDE4 inhibitor) Rsch. Triangle Park, NC (888) 825-5249

GSK573719 GlaxoSmithKline COPD Phase III (muscarinic acetylcholine Rsch. Triangle Park, NC (888) 825-5249 antagonist)

GSK573719/vilanterol GlaxoSmithKline COPD Phase III (muscarinic acetylcholine Rsch. Triangle Park, NC (888) 825-5249 antagonist/long-acting Theravance (877) 275-8479 beta2 agonist) South San Francisco, CA

GSK610677 GlaxoSmithKline COPD Phase I (inhaled p38 kinase inhibitor) Rsch. Triangle Park, NC (888) 825-5249

GSK961081 GlaxoSmithKline COPD Phase II (muscarinic antagonist/ Rsch. Triangle Park, NC (888) 825-5249 beta2 agonist) Theravance (877) 275-8479 South San Francisco, CA

GSK1325756 GlaxoSmithKline COPD Phase I (chemokine receptor Rsch. Triangle Park, NC (888) 825-5249 antagonist-2)

GSK2245840 GlaxoSmithKline COPD Phase I (SIRT1 activator) Rsch. Triangle Park, NC (888) 825-5249

Ilaris® Novartis Pharmaceuticals COPD Phase I/II completed canakinumab East Hanover, NJ (888) 669-6682

LAS 100977 Almirall COPD Phase II (LABA) Barcelona, Spain (800) 678-1605 Forest Laboratories New York, NY

levosalbutamol/ipratropium Sunovion Pharmaceuticals COPD Phase II inhalation solution Marlborough, MA (508) 481-6700

Medicines in Development COPD 2012 3 Medicines in Development for COPD

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Status*

losmapimod GlaxoSmithKline COPD Phase II (oral p38 kinase inhibitor) Rsch. Triangle Park, NC (888) 825-5249

MEDI-2338 MedImmune COPD Phase I (anti-IL-18 mAb) Gaithersburg, MD (301) 398-0000

MEDI-8968 MedImmune COPD Phase I (anti-IL-1R) Gaithersburg, MD (301) 398-0000

MK-7123 Ligand Pharmaceuticals COPD Phase II (navarixin) La Jolla, CA (858) 550-7500 Merck (800) 672-6372 Whitehouse Station, NJ

MN-166 MediciNova COPD Phase I completed (ibudilast) San Diego, CA (858) 373-1500

MN-221 MediciNova COPD Phase I (bedoradrine) San Diego, CA (858) 373-1500

NVA237 Novartis Pharmaceuticals COPD Phase III (glycopyrrolate inhalation) East Hanover, NJ (888) 669-6682

O-desulfated heparin ParinGenix COPD Phase II intravenous Tucson, AZ (617) 480-5068

olodaterol Boehringer Ingelheim COPD Phase III Pharmaceuticals (800) 243-0127 Ridgefield, CT

olodaterol/tiotropium bromide Boehringer Ingelheim COPD Phase II Pharmaceuticals (800) 243-0127 Ridgefield, CT

paclitaxel-loaded stent Broncus Technologies emphysema Phase III Mountain View, CA (650) 428-1600

PF-03715455 Pfizer COPD Phase I New York, NY (860) 732-5156

PH-797804 Pfizer COPD Phase II New York, NY (860) 732-5156

Prochymal® Osiris Therapeutics COPD Phase II remestemcel-L Columbia, MD (443) 545-1800

4 Medicines in Development COPD 2012 Medicines in Development for COPD

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Status*

PT001 Pearl Therapeutics COPD Phase II (glycopyrrolate inhalation Redwood City, CA (650) 305-2600 aerosol)

PT003 Pearl Therapeutics COPD Phase II (glycopyrrolate/formoterol Redwood City, CA (650) 305-2600 inhalation aerosol)

PT005 Pearl Therapeutics COPD Phase II (formoterol inhalation aerosol) Redwood City, CA (650) 305-2600

PUR118 Pulmatrix COPD Phase I Lexington, MA (781) 357-2333

QMF149 Novartis Pharmaceuticals COPD Phase II (indacaterol/mometasone) East Hanover, NJ (888) 669-6682

QVA149 Novartis Pharmaceuticals COPD Phase III (glycopyrrolate/indacaterol East Hanover, NJ (888) 669-6682 inhalation)

Relovair™ GlaxoSmithKline COPD Phase III vilanterol/fluticasone furoate Rsch. Triangle Park, NC (888) 825-5249 Theravance (877) 275-8479 South San Francisco, CA

RV568 RespiVert COPD Phase II London, England (800) 526-7736 Janssen Research & Development Raritan, NJ

TD-4208 Theravance COPD Phase II (LAMA) South San Francisco, CA (877) 275-8479

tetomilast Otsuka America Pharmaceutical COPD Phase II Rockville, MD (800) 562-3974

vilanterol GlaxoSmithKline COPD Phase III (long-acting beta2 agonist) Rsch. Triangle Park, NC (888) 825-5249

Veldona® Amarillo Biosciences COPD (chronic coughing) Phase II interferon-alpha Amarillo, TX www.amarbio.com

Medicines in Development COPD 2012 5 Glossary

application submitted—Application for emphysema—An enlargement of the tiny air Phase III—Extensive clinical trials to demon- marketing has been submitted to the Food and sacs of the lungs (alveoli) and the destruction strate safety and efficacy in humans. Drug Administration (FDA). of their walls, which causes structural and permanent reduction of airflow. chronic obstructive pulmonary disease (COPD)—A group of lung diseases, icluding Phase I—Safety testing and pharmacological chronic bronchitis and emphysema, in which profiling in humans. there is a persistent disruption of airflow out of the lungs and eventual hypoxemia (low level of Phase II—Effectiveness and safety testing in oxygen in the blood). 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.

Pharmaceutical Research and Manufacturers of America • 950 F Street, NW, Washington, DC 20004

6 Medicines in Development COPD 2012 Selected Facts about COPD

Selected Facts about Chronic Obstructive Pulmonary Disease (COPD) in the United States

• 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

Sources:

1. American Lung Association, www.lungusa.org

2. U.S. Centers for Disease Control and Prevention, www.cdc.gov

Medicines in Development COPD 2012 7 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 The U.S. system of new drug approvals is Administration (FDA) to begin to test the drug hospitals. Physicians monitor patients closely to perhaps the most rigorous in the world. in people. The IND shows results of previous confirm efficacy and identify adverse events. experiments; how, where and by whom the It takes 10-15 years, on average, for an New Drug Application (NDA)/Biologic new studies will be conducted; the chemical experimental drug to travel from lab to U.S. License Application (BLA). Following the structure of the compound; how it is thought patients, according to the Tufts Center for the completion of all three phases of clinical trials, to work in the body; any toxic effects found in Study of Drug Development. Only five in 5,000 a company analyzes all of the data and files an the animal studies; and how the compound compounds that enter preclinical testing make NDA or BLA with FDA if the data successfully is manufactured. All clinical trials must be it to human testing. And only one of those five demonstrate both safety and effectiveness. reviewed and approved by the Institutional is approved for sale. The applications contain all of the scientific Review Board (IRB) where the trials will be information that the company has gathered. On average, it costs a company $1.2 billion, conducted. Progress reports on clinical trials Applications typically run 100,000 pages or including the cost of failures, to get one new must be submitted at least annually to FDA and more. medicine from the laboratory to U.S. patients, the IRB. according to a 2007 study by the Tufts Center Approval. Once FDA approves an NDA or Clinical Trials, Phase I. These tests usually for the Study of Drug Development. BLA, the new medicine becomes available involve about 20 to 100 healthy volunteers. The for physicians to prescribe. A company must Once a new compound has been identified in tests study a drug’s safety profile, including the continue to submit periodic reports to FDA, the laboratory, medicines are usually devel- safe dosage range. The studies also determine including any cases of adverse reactions and oped as follows: how a drug is absorbed, distributed, metabo- appropriate quality-control records. For some lized, and excreted as well as the duration of Preclinical Testing. A pharmaceutical com- medicines, FDA requires additional trials its action. pany conducts laboratory and animal studies (Phase IV) to evaluate long-term effects. to show biological activity of the compound Clinical Trials, Phase II. In this phase, Discovering and developing safe and effective against the targeted disease, and the com- controlled trials of approximately 100 to 500 new medicines is a long, difficult, and expensive pound is evaluated for safety. volunteer patients (people with the disease) process. Biopharmaceutical companies invested assess a drug’s effectiveness and determine Investigational New Drug Application (IND). an estimated $67.4 billion in research and the early side effect profile. After completing preclinical testing, a company development in 2010. files an IND with the U.S. Food and Drug Clinical Trials, Phase III. This phase usually involves 1,000 to 5,000 patients in clinics and