PhRMA and America’s biopharmaceutical research companies are working on 54 medicines to treat chronic obstructive pulmonary disease (COPD), for the more than 13 million American adults that suffer from the disease. COPD is a progressive lower respiratory disease that encompasses two main conditions – chronic bronchitis and emphysema – COPD is characterized by obstructed airflow to the lungs that interferes with normal breathing.

1. 2012 RepoRt
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.
80
00
0
08
9
caused by smoking, other causes include air
19
20
19
20
pollution, second-hand smoke, occupational
Source: U.S. Centers for Disease dusts and chemicals, hereditary and childhood
Control and Prevention respiratory infections.

2. 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

3. 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

4. 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

5. 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

6. 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.
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
6 Medicines in Development COPD 2012

7. 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

8. 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
preclinical testing. A pharmaceutical com- lized, and excreted as well as the duration of
medicines, FDA requires additional trials
pany conducts laboratory and animal studies its action.
(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
Investigational New Drug Application (IND). assess a drug’s effectiveness and determine
an estimated $67.4 billion in research and
After completing preclinical testing, a company the early side effect profile.
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