Research in Your Backyard

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1 Research in Your Backyard Developing Cures, Creating Jobs Pharmaceutical Clinical Trials in Minnesota Dots show locations of clinical trials in the state.

2 An Overview Clinical Trials in Minnesota Biopharmaceutical research companies have conducted more than 2,400 clinical trials of new medicines since 1999 in collaboration with the state s local research institutions, including the Clinical Research Institute in Minneapolis and Plymouth, Twin Cities Clinical Research/Prism Clinical Research in Brooklyn Center, Ridgeview Research in Chaska, Prism Clinical Research in St. Paul, MAPS Applied Research Center in Edina, Minnesotta Diet Research Center/Frestedt Inc. in Clinical trials are required to get new medicines to the patients who need them. This is a complicated business since completing a clinical trial typically requires 6-7 years of effort. We must ensure the safety of each clinical trial participant to the extent possible while clearly measuring the effects of the new product. Enormous amounts of data are often collected and reviewed to evaluate the safety and efficacy of the product. Once approved for the market, medicines continue to be monitored by the companies that manufacture the products and the FDA to ensure their continued safety and efficacy. Joy Frestedt, PhD, RAC, CCTI President and CEO, Frestedt Incorporated St. Louis Park, Mercy Hospital in Coon Rapids, St. Mary s Duluth Clinic in Duluth, St. Cloud Hospital in St. Cloud, St. Paul s Heart Clinic in St. Paul, University of Minnesota School of Medicine in Minneapolis and the Mayo Clinic in Rochester. The trials have been aimed at a wide array of diseases and medical conditions, ranging from the most debilitating chronic diseases, including cancer, pain, heart disease, obesity and diabetes, to bothersome allergies, sinusitis, chronic obstructive pulmonary disease (COPD), migraine headaches, pneumonia and rare diseases affecting small patient populations. With so much clinical trial activity in the state, widespread public awareness of trials is a challenge which led to the formation of a unique coalition the Minnesota Clinical Research Alliance (MCRA). MCRA provides important clinical research education at a time when it is a challenge for biopharmaceutical companies and local research collaborators to recruit volunteers and patients often don t know about trials of new drugs. Clinical trials in Minnesota have not only been good for patients, but also the state s economy and the advancement of science and overall patient health care. 2 PhRMA Pharmaceutical Clinical Trials in Minnesota

3 Clinical research provides options for my patients who have conditions with very limited options. Not only do they have access to compounds which are otherwise unavailable, they also receive closer surveillance and disease monitoring than they otherwise would. Our clinical research program allows Kidney Specialists of Minnesota to provide our patients with treatments which far surpass the community standard of care. Dr. Daniel Ries Co-Medical Director, Twin Cities Clinical Research MCRA Making Patients Aware of Clinical Trials and Their Importance The MCRA was launched a year ago to educate the public, elected officials and the media about the importance of clinical research to patients and the health care system and the state s economy. A collaborative effort of key elements of the Minnesota medical research community, MCRA is dedicated to explaining research all over the state in understandable terms. Alliance presentations, media meetings, opinion pieces and materials stress the patient safety protections built into the clinical trial system and how trials of new drugs and medical devices are helping to advance science and, ultimately, overall patient health care. MCRA also stresses the economic impact of clinical research on a state that, in 2010, had 11 percent of all of the clinical trials conducted in the United States. Minnesota also boasts the second highest number of medical technology jobs in the nation. In the words of Dr. Gary Berman of the Clinical Research Institute, an Alliance partner, the MCRA has chosen to put collaboration above competition in the best interests of patients. We can all accomplish more by working together to promote the strength of research in Minnesota. Many of the partners in the MCRA are heavily involved in the clinical testing of new medicines in the state for a range of diseases, including infectious and respiratory conditions, cancer, asthma, migraine headaches, allergies and others. Some of the partners provide clinical research expertise and sophisticated equipment that enable biopharmaceutical companies and their local collaborators to conduct trials of new medicines. To learn about the companies that make up the Alliance, visit the website The website address of each partner is provided and at each site, explanations in easy-to-read language are provided about the important work of each organization. On some sites, information is provided on trials of new medicines that are still recruiting patients, making them potentially very important to some disease sufferers and their health care providers. MCRA partners include Agility Research, Courante Oncology, the Clinical Research Institute, Frestedt Inc., MAPS Applied Research Center (MARC), MEDTOX Laboratories, the Minnesota Center for Obesity, Metabolism & Endocrinology (MNCOME), Minnesota Diet Research Center (MDRC), Minnesota Gastroenterology, Prism Clinical Research, The Greenlight Group, LLC, Ridgeview Research and Twin Cities Clinical Research/Prism Clinical Research. The BioBusiness Alliance of Minnesota and LifeScience Alley, another bioscience support organization, collaborate with the Alliance as affiliates. Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 3

4 About Clinical Trials and Why the MCRA Mission is Important According to a 2007 survey by CenterWatch, a company that publishes information on clinical trials, patient enrollment problems delay more than 70 percent of the tests of new medicines from one to six months. Fewer than five percent of cancer patients participate in clinical trials. The educational efforts of the MCRA help to create more awareness and understanding of trials of new drugs and that gives Minnesota patients the opportunity to discuss becoming trial volunteers with their doctors. Delays in clinical trials mean drug development takes longer, costs more and patients have to wait for treatments they may desperately need. Clinical trials are conducted to help evaluate the safety and effectiveness of new medicines and generate the data the Food and Drug Administration needs to approve new treatments. A drug cannot be approved without adequate clinical testing. Clinical tests of new drugs are conducted in three pre-approval phases and account for an average of seven of the 10 to 15 years required today to research and develop a new treatment. Trials involve thousands of volunteer patients and the generation of large volumes sometimes tens of thousands of pages of technical and scientific data. Clinical trials account for 45 to 75 percent of the average $1.2 billion cost of developing one new biotechnology medicine and that s an important statistic considering that biopharmaceutical companies frequently hire local research institutions, such as members of the MCRA and the University of Minnesota School of Medicine, to conduct the tests. For some patients who are still seeking treatments that are best for them, clinical trials can be a potential therapeutic option to discuss with health care providers. Many medicines clinically tested in Minnesota and other states are cutting-edge biotechnology drugs that have the strong potential to advance science and patient health care. Biotech medicines are derived from novel biological processes that feature cells, genes and other living organisms. With biotechnology, we have the strong potential to develop safer and more effective treatments and we are improving our ability to predict, preempt and prevent diseases. From the standpoint of patient safety in clinical trials, all tests of new medicines must be reviewed and approved by an Institutional Review Board (IRB) an independent committee of health care providers, social workers, statisticians, local patient advocates and others to ensure trials are ethically conducted and patient rights protected. Many IRBs exist right here in the state of Minnesota. 4 PhRMA Pharmaceutical Clinical Trials in Minnesota

5 The Importance of Clinical Trials Since 1999, more than 2,400 clinical trials have been conducted or are being conducted in Minnesota. The clinical trials have addressed many of the leading causes of death in the United States and in Minnesota, such as cancer, heart disease and diabetes. And they ve targeted debilitating diseases that cause severe pain, such as psoriasis, rheumatoid arthritis, and epilepsy. All of these conditions contribute to health care spending in Minnesota. Minnesota clinical research has been aimed at cancer, diabetes, cardiovascular disease, HIV infection, mental and behavioral disorders, rare diseases and respiratory diseases. Minnesota, in 2010, had the highest number of investigational medical device and FDA pre-market approvals of medical devices per capita. In 2008, health care spending in Minnesota was $35.1 billion for hospital care, physician services, long term care, prescription drugs, dental services and other health care costs. Per capita spending on health care in Minnesota was $6,720 in 2008, compared to the national average of $7,166. In 2010, Minnesota was home to 11 percent of all clinical trials in the United States. Clinical Trials in Minnesota All Clinical Trials Clinical Trials Still Recruiting 2, Source: Note: Search criteria = Minnesota, Phase I, II, III; industry only. Search performed 5/24/2012. Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 5

6 Clinical Trials in Minnesota Communities Location Arthritis Cancer Cardiovascular Diabetes Crohn s Epilepsy Infectious Kidney/Liver Mental Respiratory Other Brooklyn Center Chaska Duluth Eagan Edina Fridley Minneapolis Plymouth Rochester St. Louis Park 18 1 St. Cloud St. Paul Source: Note: Search criteria = Minnesota, Phase I, II, II; industry only. Search performed 5/24/2012. See Appendix for detailed information about these clinical trials. Disease columns will not match totals in the Appendix because some clinical trials are recruiting in more than one city. 6 PhRMA Pharmaceutical Clinical Trials in Minnesota

7 Clinical Trials in Minnesota Clinical tests of new medicines are a vitally important part of the drug development and approval process they account for 45 to 75 percent of the $1.2 billion average cost of developing a new drug and are conducted to determine the safety and effectiveness of that treatment in patients. Some trials are also conducted to compare existing treatments and some are done to learn if a drug is appropriate for a different patient population, such as children. Still others are conducted to find ways to make existing approved drugs more effective and easier to use with fewer side effects. It s essential that trials be conducted properly so that clinicians and drug reviewers can develop accurate assessments of the efficacy and safety of medicines used by patients. The FDA is a vigilant regulatory agency and its pharmaceutical review officers are effective in detecting flawed information. Questionable or confusing data can lead to lengthy delays in product approval or outright FDA rejection of a new drug. clinical Trials In Minnesota Disease Clinical Trials Still Recruiting Arthritis 10 Cancer 132 Cardiovascular Disease 52 Crohn s Disease/UlcerativeColitis/ Gastrointestinal Diabetes 24 Epilepsy/Neurological Disorders 26 Infectious Diseases 30 Kidney and Liver Disorders 17 Mental Illnesses 10 Respiratory Diseases 19 Other Diseases 53 Source: Note: Search criteria = Minnesota, Phase I, II, III; industry only. Search performed 5/24/2012. Some clinical trials appear in more than one disease category. 27 Biopharmaceutical research companies are looking for the best physicians and research institutions to help design and conduct their clinical trials to determine whether medicines are safe and effective. Side effects must be welldocumented and a determination made as to whether they occur too often and are dangerous. Clinical tests involve three phases prior to market release and thousands of volunteer patients and are often conducted at multiple sites around the country. Large volumes of technical and scientific data sometimes tens of thousands of pages are generated. In Minnesota, biopharmaceutical companies arrange for trials of new medicines to be conducted by Minnesota Clinical Research Alliance partners, the state s well-respected university medical schools and science centers, including Mayo Medical School and the University of Minnesota School of Medicine, local hospitals and other institutions. According to U.S. News and World Report, Mayo Medical School ranked 26th and the University of Minnesota Medical School ranked 34th among this year s top 100 researchoriented medical schools in the United States. Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 7

8 Arthritis, the most common cause of disability in the United States, affects about 50 million adults and 300,000 children, according to the Arthritis Foundation. In Minnesota, according to the Minnesota Department of Health (MDH), approximately 995,000 adults or 26 percent of Minnesota adults have arthritis. Arthritis consists of more than 100 different diseases or conditions affecting the joints, bones, muscles and other connective tissues. There are 10 clinical trials recruiting patients in Minnesota for arthritis, specifically rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, polymyalgia rheumatica and bone loss associated with cancer treatment. Trials are being conducted at St. Paul Rheumatology in St. Paul and the Rheumatology Department at the Mayo Clinic in Rochester, among others. Cancer, the second leading cause of death in the United States, now afflicts nearly 12 million Americans, according to the National Cancer Institute. In Minnesota, more than 28,000 new cancer cases will be diagnosed this year and 9,490 victims in the state will die, according to the American Cancer Society. Currently, 132 clinical trials of new cancer medicines are recruiting patients in Minnesota. Biopharmaceutical companies are collaborating on the tests with such institutions as the Mayo Clinical Cancer Center in Rochester, the Virginia Piper Cancer Institute at Abbott Northwestern Hospital and the Masonic Cancer Center at the University of Minnesota in Minneapolis, the Park Nicollet Clinical Fravenshuh Cancer Center in St. Louis Park, St. Mary s Health System in Duluth, and the Regions Hospital Cancer Care Center in St. Paul. Cardiovascular disease is the leading cause of death in the United States and in Minnesota. According to the American Heart Association, more than 82 million Americans are affected by these diseases. In Minnesota, in 2009, more than 9,000 residents died from some form of cardiovascular disease, according to the Minnesota Department of Health. Currently, 52 cardiovascular disease clinical tests are seeking patients in Minnesota. The trials are being conducted at the Minneapolis Heart Institute at Abbott Northwestern Hospital in Minneapolis, MAPS Applied Research Center (MARC) in Edina, Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME) in Eagan, Prism Clinical Research and the St. Paul Heart Clinic in St. Paul, Mercy Hospital in Coon Rapids, St. Cloud Hospital in St. Cloud and St. Mary s Duluth Clinic in Duluth. Crohn s disease and Ulcerative colitis (inflammatory bowel disease) affect 1.4 million Americans and are evenly split between the two, according to the Crohn s and Colitis Foundation of America. Other gastrointestinal disease medicine trials that are still recruiting patients in Minnesota are targeting chronic idiopathic constipation, celiac disease, diabetes-related gastroparesis, irritable bowel syndrome and eosinophilic esophagitis. Currently, 27 clinical tests are seeking patients in Minnesota for Crohn s disease, ulcerative colitis, irritable bowel syndrome and other gastrointestinal disorders. The trials are being conducted at Ridgeview Research in Chaska, Minnesota Gastroenterology (MNGASTRO) in Plymouth, The Mayo Clinical in Rochester and Colon & Rectal Surgery Associates in Minneapolis. Diabetes affects more than 20 million Americans about 8 percent of the U.S. population and nearly one-third are unaware they have the disease. Each year, more than 26,000 Minnesotans are newly diagnosed with diabetes and it was the seventh leading cause of death in 2009, according to the Minnesota Department of Health. Currently, 24 diabetes clinical tests are seeking patients in Minnesota. The trials are being conducted at the Twin Cities Clinical Research/Prism Clinical Research in Brooklyn Center, Mayo Clinic in Rochester, the International Diabetes Center in Minneapolis, Prism Clinical Research in St. Paul, Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME) in Eagan, and Radiant Research in Edina. 8 PhRMA Pharmaceutical Clinical Trials in Minnesota

9 Epilepsy affects nearly 3 million Americans, according to the Epilepsy Foundation. The Epilepsy Foundation Minnesota estimates that one in 26 people will develop the disease at some point in their life. Other neurologic disorders targeted by clinical trials that are still recruiting include migraines, chronic low back pain (internal disc disruption, IDD), Parkinson s disease, multiple sclerosis, cerebral palsy and muscular dystrophies. Currently, there are 26 clinical trials recruiting patients in Minnesota for neurologic disorders. The trials are underway at Abbott Northwestern Hospital and the University of Minnesota in Minneapolis, MAPS Applied Research Center (MARC) in Edina, St. Cloud Hospital in St. Cloud, Prism Clinical Research and Gilette Children s Specialty Health Care in St. Paul and Medical Advanced Pain Specialists Applied Research Center in Edina, and the Minneapolis Clinic of Neurology in Golden Valley. Infectious Diseases, both newly emerging and reemerging, cause the death of at least 170,000 Americans each year, according to a 2008 report from Trust for America s Health. In 2010, 676 Minnesota residents died from infectious and parasitic diseases. There are 30 clinical trials recruiting patients in Minnesota for infectious diseases, including, aspergillosis, herpes zoster, influenza, meningococcal disease, onychomycosis, candidiasis, HIV infection, urinary tract infections, intraabdominal infections, Hepatitis B, Hepatitis C, Clostridium difficle infections, and athlete s foot (tinea pedis). Trials are being conducted at MNGASTRO (Minnesota Gastroenterology) in St. Paul, the University of Minnesota, the Clinic42 and International Travel Clinic and the Hennepin County Medical Center in Minneapolis, and the Minnesota Clinical Study Center in Fridley. Kidney and Liver Diseases are the ninth and twelfth leading causes of death in the United States and the eighth and twelfth in Minnesota. Clinical trials recruiting patients in Minnesota are aimed at polycystic kidney disease, renal impairment and insufficiency, amyloidosis, hepatorenal syndrome type 1 and membranous nephropathy, haptic veno-occlusive disease, cirrhosis, hepatic impairment and steatohepatitis and other conditions. There are 12 clinical trials for kidney diseases and 5 for liver diseases recruiting patients in Minnesota. Trials are underway at DaVita Clinical Research and the University of Minnesota in Minneapolis, Twin Cities Clinical Research/ Prism Clinical Research in Brooklyn Center, University of Minnesota Medical Center in Fairview, Children s Hospitals and Clinics of Minnesota in St. Paul, and Rochester Methodist and Mayo Clinic in Rochester. Mental illness affects nearly 60 million Americans suffering from some form of the disease from anxiety to depression to schizophrenia to eating disorders. In Minnesota, about 168,000 adults live with serious mental illness and about 56,000 children live with serious mental health conditions, according to the National Alliance on Mental Illness. Currently, 10 clinical trials are recruiting patients in Minnesota. The trials are being conducted at the Mayo Clinic in Rochester, and in Minneapolis at the Minneapolis VA Medical Center and the Ambulatory Research Center, Department of Psychiatry and the University of Minnesota Medical Center. Respiratory Disorders, such as asthma and chronic obstructive pulmonary disease (COPD), are the third leading cause of death in the United States and in Minnesota. Asthma affects more than 23 million Americans including 7 million children under the age of 18. The toll is also severe in Minnesota in 2009, about 260,000 adults and 76,000 children had asthma, according to the Minnesota Department of Health. COPD, which includes chronic bronchitis and emphysema, affects more than 14 million Americans and in Minnesota 70,600 adults over the age of 45 have COPD. Currently, 19 clinical trials of new respiratory disease medicines are recruiting patients in Minnesota. Trials are being conducted at the University of Minnesota and the Hennepin County Medical Center in Minneapolis, the Clinical Research Institute in Minneapolis and Plymouth, and the Mayo Clinic in Rochester. Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 9

10 Other diseases and medical conditions that are being targeted in Minnesota include: abdominal aneurysms allergic rhinitis amyloidosis benign prostatic hyperplasia glaucoma hemophilia lupus obesity overactive bladder peanut allergy primary immunodeficiency diseases psoriasis sleep apnea Currently, there are 52 clinical trials recruiting patients for these diseases. The trials are underway at the Clinical Research Institute in Minneapolis, Chu Vision and Minnesota Eye Consultants in Bloomington, the Mayo Clinic in Rochester, the Orthopedic Surgery Center in Bloomington and Edina, Minesota Diet Research Center/Frestedt Inc. in St. Louis Park, Abbott Northwestern Hospital and the University of Minnesota in Minneapolis, Clinical Research Institute in Plymouth, and Children s Hospitals and Clinics of Minnesota in St. Paul. Physicians and patients can find out about clinical trials being conducted across the state in collaboration with local institutions by accessing a database sponsored by the National Institutes of Health. Information on medicines in development is also available on the website of the Pharmaceutical Research and Manufacturers of America (PhRMA). 10 PhRMA Pharmaceutical Clinical Trials in Minnesota

11 Minnesota Clinical Trials of Biotechnology Drugs Many of the medicines being tested in Minnesota are cutting-edge biotechnology drugs. America s biopharmaceutical research companies are using biotechnology to develop hundreds of medicines and vaccines today. And Minnesota is one of the states where extensive new-generation research and development work is being done. Through biotechnology, new ways are being developed to not only more effectively treat disease, but also to predict, preempt, and prevent it. Biotechnology medicines are developed through biological processes using living cells or organisms, rather than traditional chemical synthesis, the mainstay of pharmaceutical development for decades. Such novel treatments use a variety of new approaches to treat disease. For example, a monoclonal antibody is a laboratory-made version of the naturally occurring immune system protein that binds to and neutralizes foreign invaders. Interferons are proteins that interfere with the ability of a cell to reproduce. Antisense drugs, meanwhile, are medicines that interfere with the communication process that tells a cell to produce an unwanted protein. In addition, nanotechnology is being used in biotechnology research to provide drugdelivery systems, new treatments, and diagnostics. Many of the medicines in clinical testing at Minnesota medical schools and research centers feature these technologies. For example: A genetically-modified virus-based vaccine to treat melanoma. A monoclonal antibody for the treatment of cancer. An antisense medicine for the treatment of cancer. A recombinant fusion protein to treat age-related macular degeneration and diabetic macular edema. A therapeutic vaccine, designed to jump-start the immune system to fight disease, is in development for lung cancer and melanoma. A fibrin sealant delivered with a novel device designed to inject the sealant directly into the affected vertebral disc to potentially heal an internal disc disruption (IDD) which has caused years of chronic low back pain. These are only a portion of the examples of new ways the nation s biopharmaceutical companies and Minnesota research institutions are working together to attack disease. The biotechnology medicines and vaccines in development promise to push the frontiers of science and potentially bring more and better treatments to patients. Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 11

12 Conclusion Biopharmaceutical companies close collaboration with clinicians and research institutions in Minnesota benefits patients, the state s economy, and the advancement of science and patient care. Clinical trial work is good business for the state s medical schools and clinical research centers and the medicines being tested are often cuttingedge cell and protein treatments with the potential to be safer and more effective than older chemical compound drugs. What s more, Minnesotans contemplating participation in clinical trials, in consultation with their doctors, have a wide range of choices nearly 400 tests of new medicines for many of the most debilitating diseases in America are underway in communities large and small all over the state and they need patient volunteers. 12 PhRMA Pharmaceutical Clinical Trials in Minnesota

13 The Drug Discovery, Development and Approval Process It takes 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. Clinical Trials Discovery/ Preclinical Testing Phase I Phase II Phase III FDA Phase IV Years Test Population Purpose Laboratory and animal studies Assess safety, biological activity and formulations File IND at FDA 20 to 100 healthy volunteers Determine safety and dosage 100 to 500 patient volunteers Evaluate effectiveness, look for side effects 1,000 to 5,000 patient volunteers Confirm effectiveness, monitor adverse reactions from long-term use File NDA/BLA at FDA Review process/ approval Additional postmarketing testing required by FDA Success Rate 5,000 compounds evaluated 5 enter trials 1 approved The Drug Development and Approval Process The U.S. system of new drug approvals is perhaps the most rigorous in the world. It takes 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, based on drugs approved from 1994 through 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 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 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 normal, 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, metabolized, 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. The average review time for the 21 new therapeutics approved by the FDA in 2010 was 14.8 months. 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. PhRMA member companies invested an estimated $49.5 billion in research and development in Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 13

14 The Good News Many Clinical Trials are Still Recruiting There are 391 clinical trials of new medicines recruiting in Minnesota. These trials target many of the chronic and debilitating diseases affecting Americans and Minnesotans. Clinical Trials in Minnesota Communities Location Arthritis Cancer Cardiovascular Diabetes Crohn s Epilepsy Infectious Kidney/Liver Mental Respiratory Other Brooklyn Center Chaska Duluth Eagan Edina Fridley Minneapolis Plymouth Rochester St. Louis Park 18 1 St. Cloud St. Paul Source: Note: Search criteria = Minnesota, Phase I, II, II; industry only. Search performed 5/24/2012. See Appendix for detailed information about these clinical trials. Disease columns will not match totals in the Appendix because some clinical trials are recruiting in more than one city. 14 PhRMA Pharmaceutical Clinical Trials in Minnesota

15 The Good News Many Clinical Trials are Still Recruiting (continued) Arthritis Institutions Conducting Clinical Trials Mayo Clinic, Rochester St. Paul Rheumatology, St. Paul Cancer Institutions Conducting Clinical Trials Children s Hospital & Clinics of Minnesota, Minneapolis Community Clinical Oncology Program; Fridley, Maplewood, St. Louis Park, St. Paul Duluth Clinic Cancer Center, Duluth Fairview Clinical Trials Services, Minneapolis Masonic Cancer Center-University of Minnesota Physicians, Minneapolis Mayo Clinical Cancer Center, Rochester Minnesota Oncology Associates; Burnsville, Coon Rapids, Edina, Fridley, Maplewood, Minneapolis, St. Paul, Waconia, Woodbury Minnesota Oncology Hematology, Minneapolis North Memorial Hubert H. Humphrey Cancer Center, Robbinsdale Park Nicollet Clinic Fravenshuh Cancer Center, St. Louis Park St. Luke s Hospital Whiteside Institute for Clinical Research, Duluth St. Mary s Duluth Clinic Health System, Duluth St. Mary s Hospital-Mayo Clinic, Rochester University of Minnesota Amplatz Children s Hospital, Minneapolis University of Minnesota Cancer Center, Minneapolis Virginia Piper Cancer Institute-Abbott Northwestern Hospital, Minneapolis Cardiovascular Disease Institutions Conducting Clinical Trials Abbott Northwestern Hospital, Minneapolis DaVita Clinical Research, Minneapolis Essentia Health, Duluth Hennepin County Medical Center, Minneapolis MAPS Applied Research Center (MARC), Edina Mayo Clinic, Rochester Mercy Hospital, Coon Rapids Minneapolis Clinic of Neurology, Robbinsdale Minneapolis Heart Institute Foundation-Abbott Northwestern Hospital, Minneapolis Minneapolis VA Health Care System, Minneapolis Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), Eagan Prism Clinical Research, St. Paul St. Cloud Hospital, St. Cloud St. Joseph s Hospital, St. Paul St. Mary s Hospital, Mayo Clinic, Rochester St. Paul Heart Clinic, St. Paul United Heart and Vascular Center, St. Paul University of Minnesota, Minneapolis Diabetes Institutions Conducting Clinical Trials Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), Eagan Prism Clinical Research, St. Paul Twin Cities Clinical Research/Prism Clinical Research, Brooklyn Center Crohn s Disease/Ulcerative Colitis Institutions Conducting Clinical Trials Colon & Rectal Surgery Associates, Minneapolis Mayo Clinic, Rochester Minnesota Gastroenterology (MNGASTRO), Plymouth Ridgeview Research, Chaska Epilepsy/Neurologic Disorders Institutions Conducting Clinical Trials Abbott Northwestern Hospital, Minneapolis Clinical Research Institute, Minneapolis, Plymouth Gilette Children s Specialty Healthcare, St. Paul Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 15

16 The Good News Many Clinical Trials are Still Recruiting (continued) MAPS Applied Research Center (MARC), Edina Medical Advanced Pain Specialists Applied Research Center, Edina Minneapolis Clinic of Neurology, Golden Valley Minnesota Epilepsy Group, St. Paul Prism Clinical Research, St. Paul St. Cloud Hospital, St. Cloud University of Minnesota Medical Center, Fairview University of Minnesota, Minneapolis Infectious Diseases Institutions Conducting Clinical Trials Clinic 42 and International Travel Clinic, Minneapolis Hennepin County Medical Center, Minneapolis HIV Program Hennepin County, Minneapolis Minnesota Clinical Study Center, Fridley Minnesota Gastroenterology (MNGASTRO), St. Paul University of Minnesota, Minneapolis Kidney and Liver Disorders Institutions Conducting Clinical Trials Children s Hospitals and Clinics of Minnesota, St. Paul DaVita Clinical Research, Minneapolis Mayo Clinic, Rochester Prism Clinical Research, St. Paul Rochester Methodist Hospital at Mayo Clinic, Rochester Twin Cities Clinical Research/Prism Clinical Research, Brooklyn Center University of Minnesota Medical Center, Fairview University of Minnesota, Minneapolis Mental Illness Institutions Conducting Clinical Trials Ambulatory Research Center, Department of Psychiatry, Minneapolis Mayo Clinic, Rochester Minneapolis VA Medical Center, Minneapolis University of Minnesota Medical Center, Fairview Respiratory Diseases Institutions Conducting Clinical Trials Clinical Research Institute, Minneapolis, Plymouth Mayo Clinic, Rochester University of Minnesota, Minneapolis Other Diseases Institutions Conducting Clinical Trials Abbott Northwestern Hospital, Minneapolis Allergy & Asthma Specialists, Minneapolis Children s Hospitals and Clinics of Minnesota, St. Paul Chu Vision, Bloomington Clinical Research Center, Plymouth Minnesota Diet Research Center (MDRC), Edina Mayo Clinic Transplant Center, Rochester Mayo Clinic, Rochester Midwest Immunology, Plymouth Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), Eagan Minnesota Clinical Study Center, Fridley Frestedt Inc., Edina Minnesota Eye Consultants, Bloomington Orthopedic Surgery Center, Bloomington, Edina University of Minnesota, Minneapolis 16 PhRMA Pharmaceutical Clinical Trials in Minnesota

17 Appendix The clinical trials listed here involve tests that have not yet started recruiting patients or are just now seeking volunteers to participate. This information is potentially valuable to patients still seeking effective treatments for their chronic diseases. It provides a new therapeutic option to discuss with physicians. Those interested in obtaining more information about certain trials can use the URL code listed for each test to log onto the clinical tests database of the National Institutes of Health. Arthritis (10 clinical trials recruiting) Study 1: Long-Term Effectiveness And Safety Of CP-690,550 For The Treatment Of Rheumatoid Arthritis Study 2: Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy up to 2 Years of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Anti-TNFα Agents Study 3: An Open Label Study for Patients With Rheumatoid Arthritis Study 4: A Study in Patients With Rheumatoid Arthritis Study 5: Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis Study 6: A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica Study 7: A Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy Study 8: Efficacy at 24 Weeks and Long Term Safety, Tolerability and Efficacy up to 2 Years of Secukinumab (AIN457) in Patients With Active Psoriatic Arthritis (PsA) Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 17

18 Study 9: Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout Study 10: Study of the Safety and Efficacy of Long-Term Rilonacept Treatment for the Prevention of Gout Flares Cancer (132 clinical trials recruiting) Study 1: A Study of Pertuzumab in Addition to Chemotherapy and Herceptin Trastuzumab) as Adjuvant Therapy in Patients With HER2-Positive Primary Breast Cancer Study 2: Study of Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE) Study 3: A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy Study 4: A Study in Second Line Metastatic Colorectal Cancer Study 5: Study of E7080 in Subjects With Advanced Endometrial Cancer and Disease Progression Study 6: An Open-Label, 2-Cohort, Multicenter, Study of E7080 in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma Study 7: Efficacy and Safety of Zoledronic Acid ( Every 4 Weeks vs. Every 12 Weeks) in Patients With Documented Bone Metastases From Bone Cancer Study 8: Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant Study 9: Efficacy & Safety Study of MORAb-004 to Treat Metastatic Colorectal Cancer Study 10: Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma Study 11: A Study of Ramucirumab in Patients With Gastric, Esophageal and Gastroesophageal Cancer Study 12: The BEACON Study (Breast Cancer Outcomes With NKTR-102) 18 PhRMA Pharmaceutical Clinical Trials in Minnesota

19 Study 13: Myelodysplastic Syndromes (MDS) Event Free Survival With Iron Chelation Therapy Study Study 14: Phase III Lucanix Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Front-line Chemotherapy Study 15: Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients Study 16: Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer Study 17: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer Study 18: Chemotherapy and Radiation in Treating Patients With Stage 3 Non-Small Cell Lung Cancer Study 19: Study of BMS Combined With Letrozole or BMS Alone in Patients With Hormone Receptor-Positive Breast Cancer and Resistance to Non-Steroidal Aromatase Inhibitors Study 20: Study of Patients With Advanced Non-Small Cell Lung Cancer Study 21: Immunotherapy Study for Surgically Resected Pancreatic Cancer Study 22: An Open-label Study of GSK Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer Study 23: Study of Abiraterone Acetate in Patients With Advanced Prostate Cancer Study 24: Phase 1/2 Safety and Tolerability Study of SNS01-T in Relapsed or Refractory Multiple Myeloma Study 25: Combination Study of BMS and Erbitux in Subjects With Advanced or Metastatic Solid Tumors Study 26: A Study for Patients With Pancreatic Cancer Study 27: Safety Study of Human Myeloid Progenitor Cells (CLT-008) After Post-remission Chemotherapy for Leukemia Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 19

20 Study 28: ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma Study 29: Study of ACE-011 to Determine Safe and Effective Dose of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Advanced Non-small Cell Lung Cancer Study 30: Multiple Ascending Dose of BMS Study 31: A Study of IMC-3G3 in Soft Tissue Sarcoma Study 32: Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL Study 33: Safety and Tolerability of HSC835 in Patients With Hematological Malignancies Study 34: Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma Study 35: A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant (The AETHERA Trial) Study 36: A Study of Onartuzumab (MetMAb) in Combination With Tarceva (Erlotinib) in Patients With Met Diagnostic-Positive Non-Small Cell Lung Cancer Who Have Received Chemotherapy For Advanced or Metastatic Disease (MetLung) Study 37: A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours Study 38: Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma Study 39: Trial of Gemcitabine/Carboplatin With or Without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects With Previously Untreated Stage IV Squamous Non-Small-Cell Lung Cancer (NSCLC) Study 40: Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer Study 41: Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma Study 42: A Study of Chemotherapy and Ramucirumab vs. Chemotherapy Alone in Second Line Non-small Cell Lung Cancer Patients Who Received Prior First Line Platinum Based Chemotherapy 20 PhRMA Pharmaceutical Clinical Trials in Minnesota

21 Study 43: Comparison of Docetaxel/Prednisone to Docetaxel/ Prednisone in Combination With OGX-011 in Men With Prostate Cancer Study 44: A Phase 1 Study of BMS (XL139) in Subjects With Advanced or Metastatic Cancer Study 45: A Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy Study 46: Randomized Study of ON Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts Study 47: Safety and Efficacy of Cryoablation for Metastatic Lung Tumors Study 48: A Study in Patients With Acute Leukemia Study 49: Efficacy and Safety of a Sunscreen Against Porfimer Sodium-induced Phototoxicity to Visible Light Study 50: GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors Study 51: A Study to Test the Ability of and Safety of GSK in Treating Langerhans Cell Histiocytosis Study 52: Study of Ruxolitinib in Pancreatic Cancer Patients Study 53: Study of Safety and Tolerability of PCI in Patients With Pancreatic Cancer Patients Receiving Treatment With Gemcitabine Study 54: Study of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial) Study 55: Phase 3 Study of Immunotherapy to Treat Advanced Prostate Cancer Study 56: A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer Study 57: A Study of Avastin (Bevacizumab) in Combination With Standard of Care Treatment in Patients With Lung Cancer Study 58: A Phase I Study of GNKG186 in Patient With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) Developing Cures, Creating Jobs A Partnership Between Biopharmaceutical Companies And State Research Institutions 21

22 Study 59: A Safety and Efficacy Study of Patients With Metastatic or Locally Advanced (Unresectable) Chondrosarcoma Study 60: Dasatinib Added to Gemcitabine for Subjects With Locally-advanced Pancreatic Cancer Study 61: Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral MLN9708 in Adult Patients With Relapsed and Refractory Multiple Myeloma Study 62: A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-kit Mutation Study 63: DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma Study 64: Study of Imprime PGG in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer Study 65: Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma Study 66: Study of MK-3475 in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK AM4) Study 67: A Study to Determine the Efficacy and Safety of Lenalidomide in Patients With Mantle Cell NHL Who Have Relapsed or Progressed After Treatment With Bortezomib or Are Refractory to Bortezomib. The EMERGE Trial Study 68: A Study of Ramucirumab (IMC-1121B) in Combination With Eribulin Versus Eribulin Alone in Patients With Breast Cancer Study 69: A Study of CDX-1127 in Patients With Select Solid Tumor Types or Hematologic Cancers Study 70: Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK AM1) Study 71: A Phase 1b Study of AMG 386 in Combination With Either Pegylated Liposomal Doxorubicin or Topotecan in Subjects With Advanced Recurrent Epithelial Ovarian Cancer Study 72: Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy Study 73: Safety Study of Human Myeloid Progenitor Cells (CLT-008) After Cord Blood Transplant for Hematologic Malignancy 22 PhRMA Pharmaceutical Clinical Trials in Minnesota