Older Americans Affecting Diseases Chronic Top

2014 REPORT 2 5 3 9 4 11 47 42 million Americans age 65 and older. million Americans age 65 15 million people in the affect could 2050 if no newby States United delay prevent, to found are medicines of the disease. the progression or stop Facts About Chronic Diseases Diseases About Chronic Facts States ...... in the United Chart in Development Medicines ...... Glossary ...... Contents ...... in the Pipeline Medicines Aging: Healthy ...... Advances Treatment Better Through Outcomes ...... Adherence .... Results Part D Delivering Medicare Drug Development/ ...... Process Approval date and hold the potential to furtherdate and hold the potential to and provide outcomes health improve in this All of the medicines savings. cost either in clinical trials or under report are and Drug Ad- Food the U.S. by review medicines The 435 (FDA). ministration include: in development • 10.9 which affects diabetes, 110 for • which disease, Alzheimer’s for 67 (CMS), Chronic Condition Data Warehouse Warehouse Data Condition Chronic (CMS), ect reﬂ counts The CCW 2012. Medicare, (CCW), only of claims fee-for-service administrative www.ccwdata.org/web/ ciaries. beneﬁ Medicare guest/medicare-tables-reports * Centers for Medicare and Medicaid Services and Medicaid Medicare for Centers * ctancy continues to climb— to ctancy continues expe As life women for years than 81 more up to men—the growing for years and 76 and older number of Americans age 65 chronic from challenges new will face such as arthritis,conditions Alzheimer’s and disease cardiovascular disease, which impact diabetes, their health, Those productivity and independence. not only impactdiseases the individu- their als living with them, but burden system care the health and cost families billions of dollars. companies research Biopharmaceutical targeting medicines 435 developing are affect- conditions chronic 15 leading and dementia, ing seniors—Alzheimer’s anemia, arthritis, hyper- benign prostatic chronic and glaucoma, plasia, cataracts obstructive chronic disease, kidney depression, pulmonary (COPD), disease hyperlipidemia, heartdiabetes, failure, and hypertension, hypothyroidism The medicines ischemic heart disease.* to in the pipeline build on the progress Biopharmaceutical Research Companies Are Companies Research Biopharmaceutical for Medicines Than 430 More Developing Older Americans Affecting Diseases Chronic Top

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Medicines in Development in Development Medicines Chronic Leading For Seniors Affecting Diseases

THE MEDICARE POPULATION AND LEADING CHRONIC DISEASES CHRONIC AND LEADING THE MEDICARE POPULATION Older Americans Older MEDICINES IN DEVELOPMENT FOR IN DEVELOPMENT MEDICINES Alzheimer’ than in more listed are Some medicines one category. Key Issues

diabetes. Some of these potential medicines utilize expanded OLDER AMERICANS knowledge and cutting-edge technology to attack diseases in different ways, and many offer new ways to treat or prevent disease. Examples of the medicines being developed for some TH EAL & H H F U M O A T

E S

M of the most common chronic conditions include:

MEDICARE V HEALTH INSURANCE

E E

D • USA • Recombinant Treatment for Heart Failure—A medicine in development for heart failure, a condition with lower survival There are about rates than those of some advanced cancers or heart attack, 49.4 MILLION is a recombinant form of a naturally occurring hormone that MEDICARE BENEFICIARIES is present in both men and women. The potential medicine works by relaxing blood vessels and reducing ﬂ uid buildup, and some evidence suggests that it can also reduce damage 16% OF ALL AMERICANS to the heart and other vital organs related to the cascade of damage associated with heart failure.

Blocking a Protein to Lower LDL Cholesterol—Several Source: The Henry J. Kaiser Family Foundation. monoclonal antibodies in development represent a potential • 62 for rheumatoid arthritis and osteoarthritis, which affect new class of lipid-lowering treatments. The potential medi- 1.5 million and 27 million Americans, respectively. cines inhibit a protein that targets low-density lipoprotein (LDL) receptors on the surface of the liver. When that pro- • 61 for heart disease—atrial ﬁ briheart failure, hypertension, tein interacts with LDL receptors, it promotes degradation of ischemic heart disease and high cholesterol. the receptor, ultimately, interfering with the clearing of LDL-

• 40 for COPD, which affects about 13 million adults, with C (LDL cholesterol) from the blood. By blocking the protein the highest prevalence rate in those over age 65. OLDER AMERICANS Research and development of new medicines is a long and risky road, where tens of thousands of compounds in early development result in only one approved for Acquired Hypothyroidism 1 patients. Even medicines that reach clinical trials have only Alzheimer's Dementia 67 a 16 percent chance of being approved. Even though the Anemia 27 stakes are high, the 435 medicines in this report provide Arthritis 62 hope to older Americans who live with these debilitating Chronic Kidney Disease chronic diseases and are seeking to live longer, more inde- 30 pendent and healthier lives. COPD 40 Depression 27 Medicines in the Pipeline Diabetes 110 Glaucoma 19 Many medicines in development today target the most com- Heart Disease 61 mon chronic conditions affecting Medicare beneﬁ ciaries—high blood pressure, high cholesterol, heart disease, arthritis and Source: 2014 PhRMA Medicines in Development for Older Americans.

2 Medicines in Development for Older Americans 2014 Key Issues

from interacting with the receptor, more LDL receptors are treat high blood pressure, the fi rst therapeutic cancer vaccine, available on the surface of liver cells to remove LDL-C from two new personalized medicines for skin cancer, and three the blood. new treatments for diabetes. Those medicines and others are transforming many diseases into treatable conditions and Next-Generation Oral Treatment for Type 2 Diabetes—A reducing the impact of chronic diseases like cardiovascular dis- medicine in development for the treatment of type 2 dia- ease, diabetes, osteoporosis and rheumatoid arthritis. In ad- betes is part of the dipeptidyl peptidase 4 (DPP-4) inhibitor dition, health outcomes continue to improve, with the use of class, with properties distinct from other approved medi- new medicines playing a large role in achieving better results. cines in this class. DPP-4 inhibitors work by stimulating the secretion of insulin and decreasing the release of glucagon • Life expectancy for men and women has increased by a (a hormone produced in the pancreas), ultimately reducing full decade since 1950, from 68.2 to 78.7 years of age in blood glucose levels. In clinical trials, the medicine was able 2011, according to the U.S. Centers for Disease Control to inhibit more than 80 percent of DPP-4 for seven days, and Prevention (CDC). making it potentially a once-weekly versus daily treatment. • The death rate for Americans has fallen by 60 percent in Inhibiting Beta-Amyloid Production in Alzheimer’s the last 75 years, reaching a record low in 2011 and almost Disease—A potential fi rst-in-class medicine inhibits beta- a full percent lower than in 2010, according to the CDC. site amyloid precursor protein cleaving enzyme (BACE), an • Death rates from cardiovascular disease fell more than 55 enzyme involved in the production of beta-amyloid peptide. percent between 1979 and 2011, according to the CDC. Beta-amyloid is believed to be involved in Alzheimer’s disease. The CDC cites factors contributing to the decline in heart Cartilage Regeneration for Osteoarthritis—An allogeneic disease and stroke deaths including better control of risks (donor) cell therapy being studied in clinical trials uses a factors, early detection, and better treatment and care, as mixture of cartilage cells that have been genetically modifi ed well as new drugs and expanded use of existing drugs. to produce the growth factor TGF-ß1 (transforming growth factor beta 1) and unmodifi ed cells. TGF-ß1 plays a critical role in the development, growth, maintenance and repair OLDER AMERICANS of cartilage in bone joints (articular cartilage) by stimulat- Most common chronic conditions in ing chondrocytes (mature cells found in cartilage). In clinical MEDICARE BENEFICIARIES trials, cartilage regeneration by the modifi ed cells has shown to be signifi cantly enhanced by the co-delivery of unmodi- 58% fi ed cells at the site of degeneration. The medicine, delivered 45% HIGH BLOOD 28% through local injection, may potentially treat not only the PRESSURE symptoms of osteoarthritis but also the causes, by promoting HIGH DIABETES the regeneration of cartilage. CHOLESTEROL Healthy Aging: Treatment Advances 31% 29% The medicines in the pipeline today follow decades of ad- HEART vances in discovery and development of innovative therapies. DISEASE ARTHRITIS In the last decade, more than 300 new medicines have been approved by the FDA, including a new class of medicines to Source: Centers for Medicare & Medicaid Services (CMS).

Medicines in Development for Older Americans 2014 3 Key Issues

OLDER AMERICANS “ Factors contributing to the decline in heart disease and stroke deaths include better control of risk factors, improved access to early detection, and better treat- >2/3 ment and care, including new drugs and of Medicare expanded uses for existing drugs.”— CDC beneficiaries and retinopathy (2.7 percent lower), according to a study have at least published in the American Journal of Managed Care.

• Improved adherence to medication among diabetes 2 + patients could prevent more than 1 million emergency chronic department visits and hospitalizations annually, potentially conditions saving $8.3 billion each year, according to a study published in Health Affairs.

Source: CMS. • A study published in Health Affairs found that if untreated hypertension patients received the recom- • Disability among seniors is down—a Harvard University mended treatment, potentially 420,000 hospitalizations study found that between 1984 and 2004/05, disability and 89,000 premature deaths could be avoided each in the elderly decreased by one-ﬁ fth. In that same period, year. A separate study published in the Journal of Gen- an elderly patient’s ability to survive a cardiovascular eral Internal Medicine found that better adherence to event without becoming disabled rose by 50 percent. antihypertensive medicines could save about 200,000 • Better outcomes in rheumatoid arthritis are achieved when lives over ﬁ ve years. treatment is initiated earlier in the disease, according to a report from Boston Healthcare Associates. Long-term data analysis found that 46 percent of patients who received OLDER AMERICANS treatment earlier in disease achieved remission compared to only 31 percent of patients treated at an advanced stage. Non-Adherence to Better Outcomes through Adherence MEDICINES

Research has shown that better and continued use of medi- costs U.S. economy cines as prescribed lead to better health outcomes. Several up to studies have illustrated the positive impact that better adherence to medicines can have on the health of patients and $ the U.S. economy. 300 • Diabetes patients who take their medicine as prescribed BILLION Annually have fewer diabetes-related complications, such as amputa- tion/ulcers (4 percent lower than nonadherent patients), re- Source: L. Osterberg and T. Blaschke. New England Journal of Medicine, 2005; M.R. DeMatteo, Medical Care, 2004. nal events (5 percent lower), neuropathy (4 percent lower),

4 Medicines in Development for Older Americans 2014 Key Issues

Now in its ninth year, Medicare Part D continues to exceed OLDER AMERICANS expectations. An extensive body of research attests to the program’s successes.

• Ninety percent of Medicare beneﬁ ciaries receive comprehensive prescription drug coverage. Even more, 90 percent of Part D enrollees are satisﬁ ed with their coverage, according to a 2012 Medicare Today survey.

• Part D represented only 10% of Medicare spending in 2012, according to the Congressional Budget Ofﬁ ce (CBO). Better Health IMPROVED AND • The Congressional Budget Ofﬁ ce (CBO) recently reduced Fewer Hospital its 10-year forecast for Part D spending by $56 billion. Adherence = That reduction follows three consecutive years of 10-year ADMISSIONS spending reductions by more than $100 billion.

Source: L. Osterberg and T. Blaschke, New England Journal of Medicine, 2005. • Based on a sizable body of research, the CBO has re- • According to a study published in the American Journal cently adopted an historic scoring change that will credit of Managed Care, Medicare will realize more than $26.9 Medicare policies that increase the use of medicines with billion in savings from 2013-2022, driven by reductions in savings on other Medicare costs. Part A and B expenditures associated with improved con- • Harvard researchers report savings on hospital and skilled gestive heart failure (CHF) medication adherence following nursing facility costs of about $1,200 per newly insured the implementation of Part D. Achieving recommended Part D beneﬁ ciary in 2007. That equals overall Medicare levels of adherence (proportion of days covered of 80 percent or higher) among Part D enrollees with CHF could yield $22.4 billion in federal savings through 2022. OLDER AMERICANS • Following implementation of Part D, monthly Medicare Part A and B spending was 10 percent to 12 percent lower for high adhering patients taking statins, ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB), according to a study published in Health Services Research. The same savings were not observed for nonadherent beneﬁ ciaries. 90% Medicare Part D Delivering Results of beneficiaries ARE SATISFIED Just as adherence to medicines is essential to the successful prevention, management and treatment of disease, access to with the program a range of medicines across therapeutic categories is critical to maintaining the improved health outcomes and cost savings we have seen in recent years. The Medicare prescription drug program (Part D) is answering that call with great results. Source: Congressional Budget Office (CBO).

Medicines in Development for Older Americans 2014 5 Key Issues

Medicines in Development By Disease and Phase Some medicines are listed in more than one category.

Application Acquired Hypothyroidism 1 Submitted Phase III Alzheimer’s 67 Phase II Anemia 27 Phase I

Arthritis 62

CKD 30

COPD 40

Depression 27

Diabetes 110

Glaucoma 19

Heart Disease 61

savings of $13.4 billion, more than one-fourth of Part D’s total cost during its ﬁ rst full year. OLDER AMERICANS

• According to a study published in Health Affairs, every additional dollar spent on medicines for adherent patients C OS with congestive heart failure, high blood pressure, diabe- T P tes and high cholesterol generated $3 to $10 in savings R on emergency room visits and hospitalizations. PART D costs O J

Part D has been a success for seniors and taxpayers due to $ C T I

its market-based, competitive structure, in which prices are 350 O negotiated by large private plans—the same plans used by BILLION N corporate employers and insurers—on behalf of seniors and LESS taxpayers. than initially expected

Medicare Part D stands as an example of how a market- based health care program runs efﬁ ciently and delivers the services and treatments it promised. The more than 435 Source: CBO. medicines in the pipeline targeting myriad chronic diseases provide new hope to older Americans seeking to live longer, more independent and healthier lives. Programs such as Medicare Part D help ensure that seniors have access to the medicines they need to prevent, manage and treat disease.

6 Medicines in Development for Older Americans 2014 Key Issues

Selected Facts About Chronic Diseases Affecting Older Americans

Alzheimer’s Disease and Other Dementias1 • In 2009, there were 15,600 hospitalizations with RA listed as the principal diagnosis with total hospital charges • An estimated 5.4 million Americans have Alzheimer’s of $545 million (mean charge of $35,000 per person). disease (AD). Today, someone in America develops AD Women and people ages 45 and older accounted for the every 68 seconds. By 2050, there is expected to be one majority of those stays.4 new case of AD every 33 seconds, or nearly a million new cases per year, and AD prevalence is projected to be 11 Cataracts5 million to 16 million. • Most cataracts are related to aging and are very common • AD is the sixth leading cause of death in the United in older people. By age 80, more than half of all Ameri- States and the fi fth leading cause of death in Americans cans either have a cataract or have had cataract surgery. age 65 and older. People can have an age-related cataract in their 40s and 50s, but during middle age, most cataracts are small and • Medicare payments for services to benefi ciaries age 65 do not affect vision. It is after age 60 that most cataracts and older with AD and other dementias are three times steal vision. as great as payments for benefi ciaries without those conditions, and Medicaid payments are 19 times as great. In 2012, payments for health care, long-term care, and Chronic Condition Co-Morbidity hospice services for people age 65 and older with AD and • Nearly 92 percent of older adults have at least one other dementias were estimated to be $200 billion (not chronic condition, and 77 percent have at least two.6 including the contributions of unpaid caregivers, which • Four chronic conditions—heart disease, cancer, stroke, were valued at more than $210 billion). and diabetes—cause almost two thirds of all deaths 6 Anemia2 each year. • The frequency of anemia varies depending on age, sex, • Stroke and heart failure are highly co-morbid conditions and overall health. For older adults, age 65 years and with about 55 percent of Medicare benefi ciaries with those over, around 10 percent have anemia. For older adults re- conditions having 5 or more other chronic conditions.7 siding in a nursing-home, about 50 percent have anemia. • High cholesterol was the most common chronic condition among benefi ciaries with at least 2 chronic conditions, Arthritis while stroke was the most common condition among the 3 • Some 52.5 million U.S. adults suffer from arthritis. costliest co-occurring conditions.7 From 2010-2012, 49.7 percent of adults age 65 or older reported an arthritis diagnosis.4 • Among benefi ciaries with at least three chronic conditions, high cholesterol and high blood pressure were the most • About 27 million people in America have osteoarthritis. prevalent, and stroke and chronic kidney disease were Common risk factors include increasing age, obesity, pre- the costliest.7 vious joint injury, overuse of the joint, weak thigh muscles, and genetics.3 Chronic Kidney Disease • About 1.5 million people in the United States have rheu- • Chronic kidney disease (CKD) affects 26 million American matoid arthritis (RA). Nearly three times as many women adults and millions of others are at increased risk.8 The have the disease as men. In women, RA most commonly chance of having CKD increases after age 50 and is most begins between ages 30 and 60. In men, it often occurs common among adults older than age 70.4 later in life.3

Medicines in Development for Older Americans 2014 7 Key Issues

• Approximately 1 in 3 adults with diabetes and 1 in 5 Depression adults with high blood pressure have CKD. Other risk • Depression affects more than 6.5 million of the 35 mil- factors for CKD include cardiovascular disease and high lion Americans age 65 years and older. Most people in cholesterol, which are risk factors more common in this stage of life with depression have been experiencing older age.4 episodes of the illness during much of their lives. For oth- • Diabetes and hypertension also are the leading causes ers, depression has a ﬁ rst onset in late life—even people 10 of end-stage renal disease (ESRD). In 2011, diabetes or in their 80s and 90s. hypertension was listed as the primary cause for 7 of 10 • Depression is the single most signiﬁ cant risk factor for new cases of ESRD in the United States, which is more suicide in the elderly population.10 The population over common among adults over age 70.4 age 65 accounts for more than 25 percent of the nation’s Chronic Obstructive Pulmonary Disease9 suicides. White men over age 80 are six times more likely to commit suicide than the general population.11 Older • An estimated 12.7 million U.S. adults have been di- women are at a greater risk for suicide because women agnosed with chronic obstructive pulmonary disease in general are twice as likely as men to become seriously (COPD) [emphysema and chronic bronchitis]; however, depressed.10 research has indicated that COPD is underdiagnosed and that up to 24 million Americans have evidence of im- Diabetes12 paired lung function. • A total of 25.8 million children and adults in the United • In 2011, 4.7 million Americans reported ever being diag- States—8.3 percent of the population—have diabetes. nosed with emphysema, a lifetime prevalence rate of 20.2 Of that total, 10.9 million are age 65 or older. That’s per 1,000 people. More than 90 percent of emphysema 26.9 percent of all people in that age group who have cases were in individuals over the age of 45. diabetes.

• More than 10 million Americans reported a physician • The total costs of diagnosed diabetes in the United diagnosis of chronic bronchitis in 2011 with almost 70 States in 2012 were $245 billion: $176 billion for direct percent of cases occurring in those over age 45. Preva- medical costs and $69 billion in reduced productivity. lence rates increased with age; they were lowest among 13 those 18-44 (28.6 per 1,000 people) and highest among Glaucoma those age 65 and older (64.2 per 1,000 people). • Everyone is at risk for glaucoma from babies to senior citizens. Older people are at a higher risk for glaucoma, • COPD is an important cause of hospitalization in the but babies can be born with glaucoma (approximately 1 U.S. older population. Approximately 65 percent of out of every 10,000 babies born in the United States). hospital discharges were in the age 65 and older population in 2010. The discharge rate for the population over • More than 2.2 million Americans are estimated to have age 65 (114.1 per 10,000 people) was more than four glaucoma, but only half of them know they have it. times higher than that in the 45-64 age group (28.6 per 10,000 people). • In the United States, more than 120,000 are blind from glaucoma, accounting for up to 12 percent of all cases of • COPD takes a heavy toll on our economy. The national blindness. projected annual cost for COPD in 2010 was $49.9 billion. That included $29.5 billion in direct health care • In terms of Social Security beneﬁ ts, lost income tax rev- expenditures, $8.0 billion in indirect morbidity (lost pro- enues, and health care expenditures, glaucoma costs the ductivity due to illness) costs and $12.4 billion in indirect U.S. government more than $1.5 billion annually. mortality (productivity lost due to early death) costs.

8 Medicines in Development for Older Americans 2014 Facts

Heart Failure • More than 348,000 American deaths in 2009 included high blood pressure as a primary or contributing cause— • Heart failure (HF) has been singled out as an epidemic that’s 1,000 deaths each day. and is a staggering clinical and public health problem, associated with signiﬁ cant mortality, morbidity, and health- • High blood pressure costs the nation $47.5 billion each care expenditures, particularly among those ages 65 and year, including the cost of health care services, medications 14 older. About 5.1 million people in the United States to treat high blood pressure, and missed days of work. have heart failure.4 Hypothyroidism15 • For the 60–79-year-old age group, 7.8 percent of men and 4.5 percent of women have heart failure. For those • Hypothyroidism , a disorder that occurs when the thyroid age 80 and older, 8.6 percent of men and 11.5 percent of gland does not make enough thyroid hormone to meet women have heart failure.14 the body’s needs, affects about 4.6 percent of the U.S. population age 12 and older. Women are much more likely • In 2000 and 2010, there were 1 million hospitalizations than men to develop hypothyroidism. The disease is also for heart failure, and most of them were for those ages more common among people older than age 60. 65 and older.4

• Heart failure costs the nation an estimated $32 billion Ischemic Heart Disease each year, including the cost of health care services, medi- (Coronary Heart Disease) cations to treat heart failure, and missed days of work.4 • Heart disease is the leading cause of death for both men and women. About 600,000 people die of heart dis- Hyperlipidemia (High Blood Cholesterol)4 ease in the United States every year—that’s 1 in every 4 4 • People with high blood cholesterol have about twice the deaths. risk of heart disease as people with lower levels. • Coronary heart disease (CHD) is the most common type 4 • Some 71 million American adults (33.5 percent) have high of heart disease, killing nearly 380,000 people annually. low-density lipoprotein (LDL), or “bad,” cholesterol. About 80 percent of people who die of CHD are age 65 or older.14 • Only 1 out of every 3 adults with high LDL cholesterol has the condition under control. Less than half of adults • For the 60–79 age group, 21.1 percent of men and 10.6 with high LDL cholesterol get treatment. percent of women have CHD. For the age 80 and older age group, 34.6 percent of men and 18.6 percent of 14 Hypertension (High Blood Pressure)4 women have CHD. • Some 67 million American adults (31 percent) have high • Coronary heart disease alone costs the United States blood pressure—that’s 1 in every 3 adults. Only about $108.9 billion each year, including the cost of health care half (47 percent) of people with high blood pressure have services, medications, and lost productivity.4 their condition under control.

• Women are about as likely as men to develop high blood pressure during their lifetimes; however, for people younger than age 45, the condition affects more men than women. For people age 65 and older, high blood pressure affects more women than men.

Medicines in Development for Older Americans 2014 9 Facts

Sources: 1. Alzheimer’s Association, www.alz.org 9. American Lung Association, www.lungusa.org 2. Anemia Organization, www.anemia.org/resources/ 10. National Alliance for Mental Illness, www.nami.org education-kit 11. Geriatric Mental Health Foundation, 3. Arthritis Foundation, www.arthritis.org www.gmhfonline.org 4. U.S. Centers for Disease Control and Prevention, 12. American Diabetes Association, www.diabetes.org www.cdc.gov 13. Glaucoma Research Foundation, www.glaucoma.org 5. National Eye Institute, www.nei.nih.gov 14. American Heart Association, 6. National Council on Aging, www.ncoa.org www.circres.ahajournals.org 7. Centers for Medicare & Medicaid Services (CMS), 15. National Institute of Diabetes and Digestive and Chronic Conditions Among Medicare Beneﬁ ciaries, Kidney Diseases, www.niddk.nih.gov Chartbook: 2012 Edition, www.cms.gov 8. National Kidney Foundation, www.kidney.org

10 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Acquired Hypothyroidism

Product Name Sponsor Indication Development Phase*

BCT303 Intellectual Property Executives (IPE) hypothyroidism Phase II (liothyronine sustained release) Kingsport, TN www.ipeamerica.com

Alzheimer’s Disease and Dementia

Product Name Sponsor Indication Development Phase*

AAB-003/PF-05236812 Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase I (beta-amyloid protein inhibitor Research & Development www.janssenrnd.com mAb) South San Francisco, CA www.p zer.com P zer New York, NY

AC-1204 Accera mild to moderate Alzheimer’s disease Phase II/III (glucose stimulant) Broom eld, CO www.accerapharma.com

AD02 vaccine A ris Alzheimer’s disease Phase II (amyloid-beta protein inhibitor) Vienna, Austria www.a ris.com GlaxoSmithKline www.gsk.com Rsch. Triangle Park, NC

ALZ-801 Alzheon Alzheimer’s disease Phase I (tramiprosate prodrug) Lexington, MA www.alzheon.com

APH-0703 Aphios Alzheimer’s disease Phase II (protein kinase C stimulant) Woburn, MA www.aphios.com

ARC029 Archer Pharmaceuticals Alzheimer’s disease Phase I/II (nilvadipine) Sarasota, FL www.archerpharma.com

ARC031 Archer Pharmaceuticals Alzheimer’s disease Phase I (soluble amyloid reducing/clearing Sarasota, FL www.archerpharma.com agent)

AVN 101 Avineuro Pharmaceuticals Alzheimer’s disease Phase II (serotonin 5-HT6 receptor San Diego, CA www.avineuro.com antagonist)

AVN 322 Avineuro Pharmaceuticals Alzheimer’s disease Phase I (serotonin 6 receptor antagonist) San Diego, CA www.avineuro.com

AVP-923 Avanir Pharmaceuticals agitation in Alzheimer’s disease Phase II (dextromethorphan/quinidine Aliso Viejo, CA www.avanir.com xed-dose combination)

*For more information about a speci c medicine or company in the report, please use the website provided. Medicines in Development for Older Americans 2014 11 Medicines in Development for Older Americans

Alzheimer’s Disease and Dementia

Product Name Sponsor Indication Development Phase*

AZD3293 Astex Pharmaceuticals Alzheimer’s disease Phase I (beta secretase) Dublin, CA www.astx.com AstraZeneca www.astrazeneca.com Wilmington, DE

BACE inhibitor Janssen Research & Development Alzheimer’s disease Phase I Raritan, NJ www.janssenrnd.com Shionogi www.shionogi.com Florham Park, NJ

BACE1 protein inhibitor Boehringer Ingelheim Alzheimer’s disease Phase I Pharmaceuticals www.boehringer-ingelheim.com Ridge eld, CT www.vitaepharma.com Vitae Pharmaceuticals Fort Washington, PA

BAN2401 Biogen Idec early-stage Alzheimer’s disease Phase II (amyloid beta-protein inhibitor) Cambridge, MA www.biogenidec.com Eisai www.eisai.com Woodcli Lake, NJ

BIIB037 Biogen Idec Alzheimer’s disease Phase I (human anti-amyloid beta mAb) Cambridge, MA www.biogenidec.com

bisnorcymserine QR Pharma moderate to severe Alzheimer’s Phase I (BNC) Berwyn, PA disease www.qrpharma.com

brexpiprazole Lundbeck agitation in Alzheimer’s disease Phase III (dopamine partial agonist) Deer eld, IL (see also depression) www.lundbeck.com Otsuka Pharmaceutical www.otsuka.com Rockville, MD

bryostatin 1 Neurotrope BioScience Alzheimer’s disease Phase II Plantation, FL www.neurotropebioscience.com

CAD106 Novartis Pharmaceuticals Alzheimer’s disease Phase II (amyloid beta-protein inhibitor) East Hanover, NJ www.novartis.com

CERE-110 Sangamo BioSciences Alzheimer’s disease Phase II (AAV-NGF) Richmond, VA www.sangamo.com

CHF-5074 CereSpir Alzheimer’s disease Phase II (amyloid beta-protein inhibitor) New York, NY

CPC-201 Chase Pharmaceuticals Alzheimer’s disease Phase I Washington, DC www.chasepharmaceuticals.com

crenezumab Genentech Alzheimer’s disease Phase II (anti-amyloid-beta mAb) South San Francisco, CA www.gene.com

12 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Alzheimer’s Disease and Dementia

Product Name Sponsor Indication Development Phase*

donepezil/memantine Adamas Pharmaceuticals moderate to severe Alzheimer’s application submitted extended release Emeryville, CA disease www.adamaspharma.com ( xed-dose combination) Forest Laboratories www.frx.com New York, NY

E2609 Biogen Idec Alzheimer’s disease Phase I (BACE1 protein inhibitor) Cambridge, MA www.biogenidec.com Eisai www.eisai.com Woodcli Lake, NJ

ELND005 Transition Therapeutics agitation and aggression in Phase II (amyloid beta-protein inhibitor) Toronto, Canada Alzheimer’s disease www.transitiontherapeutics.com (Fast Track)

encenicline FORUM Pharmaceuticals Alzheimer’s disease Phase III (alpha7 nicotinic acetylcholine Watertown, MA www.forumpharma.com receptor agonist)

FRM-0962 FORUM Pharmaceuticals Alzheimer’s disease Phase II (gamma secretase modulator) Watertown, MA www.forumpharma.com

gantenerumab Roche early-stage Alzheimer’s disease Phase III (RG1450) Nutley, NJ www.roche.com

GSK2647544 GlaxoSmithKline Alzheimer’s disease Phase I (Lp-PLA2 inhibitor) Rsch. Triangle Park, NC www.gsk.com

HT-0712 Dart NeuroScience age-associated memory impairment Phase II (PDE4 inhibitor) San Diego, CA www.dartneuroscience.com

immune globulin Grifols Alzheimer’s disease Phase II/III Barcelona, Spain www.grifols.com

JNJ-54861911 Janssen Research & Development Alzheimer’s disease Phase I Raritan, NJ www.janssenrnd.com

KU-046 Kareus Therapeutics Alzheimer’s disease Phase I (amyloid beta-protein modulator) La Chaux-de-Fonds, Switzerland www.kareustherapeutics.com

Lu AE58054 Lundbeck Alzheimer’s disease (cognition) Phase III (5-HT6 receptor antagonist) Deer eld, IL www.lundbeck.com Otsuka America Pharmaceutical www.otsuka.com Rockville, MD

LY3002813 Eli Lilly Alzheimer’s disease Phase I (N3pG-AB mAb) Indianapolis, IN www.lilly.com

MEDI1841 AstraZeneca mild-moderate Alzheimer’s disease Phase I Wilmington, DE www.astrazeneca.com

Medicines in Development for Older Americans 2014 13 Medicines in Development for Older Americans

Alzheimer’s Disease and Dementia

Product Name Sponsor Indication Development Phase*

MK-7622 Merck Alzheimer’s disease Phase II Whitehouse Station, NJ www.merck.com

MK-8931 Merck Alzheimer’s disease Phase III (BACE1 protein inhibitor) Whitehouse Station, NJ www.merck.com

MSDC-0160 Metabolic Solutions Development Alzheimer’s disease Phase II (mTOT modulator) Company www.msdrx.com Kalamazoo, MI

NAV4694 Navidea Biopharmaceuticals Alzheimer’s disease (diagnosis) Phase III ( uorine-18 labeled precision Dublin, OH www.navidea.com radiopharmaceutical)

NAV5001 Navidea Biopharmaceuticals dementia with Lewy bodies Phase II (123I-labelled imaging agent) Dublin, OH (diagnosis) www.navidea.com

NIC5-15 Humanetics Alzheimer’s disease Phase II (amyloid precursor protein Minneapolis, MN www.humaneticscorp.com secretase inhibitor)

Pepticlere™ ProteoTech Alzheimer’s disease Phase I DP-74 peptide nasal delivery Kirkland, WA www.proteotech.com

PF-05212377 P zer Alzheimer’s disease Phase II (SAM-760) New York, NY www.p zer.com

pioglitazone Takeda Pharmaceuticals prevention of Alzheimer’s disease Phase III (low dose) Deer eld, IL in people with genetic risk variations www.takeda.com Zinfandel Pharmaceuticals Chapel Hill, NC

pioglitazone companion diagnostic Takeda Pharmaceuticals Alzheimer’s disease (diagnosis) Phase III (AD4833/TOMM40) Deer eld, IL www.takeda.com Zinfandel Pharmaceuticals Chapel Hill, NC

Posiphen® QR Pharma early Alzheimer’s disease Phase II R-phenserine Berwyn, PA www.qrpharma.com

PTI-80 ProteoTech Alzheimer’s disease Phase I completed (amyloid-beta-protein/tau protein Kirkland, WA www.proteotech.com inhibitor)

RG1577 Roche Alzheimer’s disease Phase II (MAO-B inhibitor) Nutley, NJ www.roche.com

rilapladib GlaxoSmithKline Alzheimer’s disease Phase II (Lp-PLA2 inhibitor) Rsch. Triangle Park, NC www.gsk.com

14 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Alzheimer’s Disease and Dementia

Product Name Sponsor Indication Development Phase*

RVX-208 Resverlogix Alzheimer’s disease Phase I completed (BET protein inhibitor) Calgary, Canada www.resverlogix.com

SAR228810 Sano US Alzheimer’s disease Phase I (anti-proto brillar AB mAb) Bridgewater, NJ www.sano .com

sGC-1061 sGC Pharma Alzheimer’s disease Phase I (nomethiazole) Wellesley, MA www.sgcpharma.com

solanezumab Eli Lilly mild Alzheimer’s disease Phase III (amyloid-beta protein inhibitor) Indianapolis, IN www.lilly.com

ST101 Sonexa Therapeutics Alzheimer’s disease Phase II completed San Diego, CA www.sonexa.com

SUVN-502 Suvun Life Sciences Alzheimer’s disease Phase I (5-HT6 receptor antagonist) Hyderabad, India www.suven.com

SYN120 Biotie Therapies Alzheimer’s disease Phase I completed (dual 5-HT6 and 2A receptor South San Francisco, CA www.biotie.com antagonist)

T3D-959 T3D Therapeutics Alzheimer’s disease Phase I completed (dual PPAR agonist) Rsch. Triangle Park, NC www.t3dtherapeutics.com

T-817MA Toyama Chemical Alzheimer’s disease Phase II (amyloid beta-protein inhibitor) Tokyo, Japan www.toyama-chemical.co.jp

tau imaging agent Avid Radiopharmaceuticals Alzheimer’s disease (diagnosis) Phase II (18F-AV-1451) Philadelphia, PA www.lilly.com Eli Lilly Indianapolis, IN

TC-1734 Targacept Alzheimer’s disease Phase II (ispronicline) Winston-Salem, NC www.targacept.com

TPI-287 Cortice Biosciences Alzheimer’s disease Phase II (next generation taxane) New York, NY www.corticebio.com

TRx0237 TauRx Pharmaceuticals Alzheimer’s disease, Phase III (tau aggregation inhibitor) Singapore frontotemporal dementia www.taurx.com

TTP488 Transtech Pharma Alzheimer’s disease Phase II (RAGE inhibitor) High Point, NC (Fast Track) www.ttpharma.com

TTP4000 Transtech Pharma Alzheimer’s disease Phase I (IgG and RAGE inhibitor) High Point, NC www.ttpharma.com

UB-311 United Biomedical mild to moderate Alzheimer’s Phase II (liquid intramuscular amyloid beta Hauppauge, NY disease www.unitedbiomedical.com protein inhibitor vaccine)

Medicines in Development for Older Americans 2014 15 Medicines in Development for Older Americans

Anemia

Product Name Sponsor Indication Development Phase*

ACE-536 Acceleron Pharma anemia in patients with Phase II (TGF-beta superfamily protein Cambridge, MA myelodysplastic syndrome www.acceleronpharma.com inhibitor) Celgene www.celgene.com Summit, NJ

Aes-103 AesRx sickle cell anemia Phase I/II ORPHAN DRUG Newton, MA www.aesrx.com

AGS-348 Agios Pharmaceuticals hereditary haematologic anemia Phase I (PK modulator) Cambridge, MA www.agios.com

AKB-6548 Akebia Therapeutics anemia associated with chronic Phase II (HIF-PH inhibitor) Cambridge, MA kidney disease www.akebia.com

Epodure™ Medgenics anemia associated with chronic Phase II erythropoietin gene therapy Wayne, PA kidney disease www.medgenics.com

epoetin alfa biosimilar Sandoz anemia associated with chronic Phase III Princeton, NJ kidney disease www.us.sandoz.com

epoetin zeta Hospira anemia in chronic renal failure Phase III Lake Forest, IL www.hospira.com

glutamine Emmaus Medical sickle cell anemia Phase III ORPHAN DRUG Torrance, CA (Fast Track) www.emmausmedical.com

GSK1278863 GlaxoSmithKline anemia associated with chronic Phase II (prolyl hydroxylase inhibitor) Research Triangle Park, NC renal disease and perioperative risk www.gsk.com reduction

hepcidin mAb Eli Lilly anemia Phase I Indianapolis, IN www.lilly.com

HM10760A Hanmi Pharmaceutical anemia Phase I completed (erythropoietin long acting) Seoul, South Korea www.hanmipharm.com

iron isomaltoside 1000 Pharmacosmos iron de ciency anemia Phase III Holbaek, Denmark www.pharmacosmos.com

JTZ- 951 Akros Pharma anemia associated with chronic Phase I (HIF-PHD inhibitor) Princeton, NJ kidney disease www.akrospharma.com Japan Tobacco Tokyo, Japan

KRX-0502 Keryx Biopharmaceuticals hyperphosphatemia associated with application submitted (ferric citrate) New York, NY chronic kidney disease www.keryx.com ------iron de ciency anemia associated Phase II with chronic kidney disease www.keryx.com

16 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Anemia

Product Name Sponsor Indication Development Phase*

LentiGlobin® bluebird bio beta-thalassemia Phase I/II b-globin gene therapy Cambridge, MA www.bluebirdbio.com

LY2928057 Eli Lilly anemia Phase II (ferroportin mAb) Indianapolis, IN www.lilly.com

molidustat Bayer HealthCare Pharmaceuticals anemia associated with chronic Phase II (HIF-PH inhibitor) Whippany, NJ renal failure www.bayerpharm.com

MST-188 Mast Therapeutics sickle cell anemia Phase III ORPHAN DRUG San Diego, CA www.masttherapeutics.com

NiCord® Gamida Cell sickle cell anemia, thalassemia Phase I/II stem cell therapy Jerusalem, Israel www.gamida-cell.com

NKTT-120 NKT Therapeutics sickle cell anemia Phase I Waltham, MA www.nktrx.com

Promacta® GlaxoSmithKline aplastic anemia Phase II eltrombopag Research Triangle Park, NC www.gsk.com

rivipansel P zer vaso-occlusive crisis associated with Phase II (Pan-selectin antagonist) New York, NY sickle cell anemia www.p zer.com

roxadustat AstraZeneca anemia associated with chronic Phase III (FG-4592) Wilmington, DE kidney disease www.astrazeneca.com FibroGen www. brogen.com San Francisco, CA

SelG1 Selexys Pharmaceuticals sickle cell anemia Phase I/II (Pan selectin inhibitor) Oklahoma City, OK www.selexys.com ORPHAN DRUG

sotatercept Acceleron Pharma chemotherapy-induced anemia Phase II/III Cambridge, MA www.acceleronpharma.com Celgene www.celgene.com Summit, NJ ------anemia associated with end-stage Phase II renal disease www.acceleronpharma.com www.celgene.com

ST10 Shield Therapeutics iron de ciency anemia Phase III (ferric maltol) London, United Kingdom www.shieldtherapeutics.com

Triferic™ Rockwell Medical Technologies iron de ciency anemia application submitted soluble ferric pyrophosphate Wixom, MI www.rockwellmed.com

Medicines in Development for Older Americans 2014 17 Medicines in Development for Older Americans

Arthritis

Product Name Sponsor Indication Development Phase*

ABP 501 Amgen rheumatoid arthritis Phase III (adalimumab biosimilar) Thousand Oaks, CA www.amgen.com

ABT-122 AbbVie rheumatoid arthritis Phase I (dual IL-17/TNF inhibitor) North Chicago, IL www.abbvie.com

ABT-494 AbbVie rheumatoid arthritis Phase II (JAK1/JAK2/JAK3 inhibitor) North Chicago, IL www.abbvie.com

ABT-981 AbbVie osteoarthritis of the knee Phase II (IL-1 alpha/IL-1 beta inhibitor) North Chicago, IL www.abbvie.com

ALX-0061 AbbVie rheumatoid arthritis Phase I/II (IL-6 receptor modulator) North Chicago, IL www.abbvie.com Ablynx www.ablynx.com Ghent, Belgium

Ampion™ Ampio Pharmaceuticals osteoarthritis of the knee Phase III Greenwood Village, CO www.ampiopharma.com

ASP015K Astellas Pharma rheumatoid arthritis Phase II (JAK inhibitor) Tokyo, Japan www.astellas.com Janssen Research & Development www.janssenrnd.com Raritan, NJ

baricitinib Eli Lilly rheumatoid arthritis Phase III (JAK1/JAK2 inhibitor) Indianapolis, IN (see also chronic kidney disease) www.lilly.com Incyte www.incyte.com Wilmington, DE

BI 655064 Boehringer Ingelheim Pharmaceuticals rheumatoid arthritis Phase I (CD40 antigen inhibitor) Ridge eld, CT www.boehringer-ingelheim.com

BI 695500 Boehringer Ingelheim Pharmaceuticals rheumatoid arthritis Phase III (rituximab biosimilar) Ridge eld, CT www.boehringer-ingelheim.com

BI 695501 Boehringer Ingelheim Pharmaceuticals rheumatoid arthritis Phase I (adalimumab biosimilar) Ridge eld, CT www.boehringer-ingelheim.com

BT-061 AbbVie rheumatoid arthritis Phase II (tregalizumab) North Chicago, IL www.abbvie.com

Btk inhibitor Pharmacyclics rheumatoid arthritis Phase I Sunnyvale, CA www.pharmacyclics.com

cadherin-11 Adheron Therapeutics rheumatoid arthritis Phase I completed (SDP051) Berkeley, CA www.adherontherapeutics.com

18 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Arthritis

Product Name Sponsor Indication Development Phase

CC-292 Celgene rheumatoid arthritis Phase II (Btk inhibitor) Summit, NJ www.celgene.com

CCX354 ChemoCentryx rheumatoid arthritis Phase I (CCR1 chemokine receptor) Mountain View, CA www.chemocentryx.com

CEP-41750 Mesoblast refractory rheumatoid arthritis Phase II (stem cell therapy) New York, NY www.mesoblast.com

CF101 Can-Fite Pharma rheumatoid arthritis Phase II (adenosine A3 receptor agonist) Waltham, MA (see also glaucoma) www.can te.com

CFZ533 Novartis Pharmaceuticals rheumatoid arthritis Phase I East Hanover, NJ www.novartis.com

clazakizumab Bristol-Myers Squibb rheumatoid arthritis Phase II (BMS-945429) Princeton, NJ www.bms.com

CNTO 6785 Janssen Research & Development rheumatoid arthritis Phase II (IL-17A modulator) Raritan, NJ (see also COPD) www.janssenrnd.com

Dekavil P zer rheumatoid arthritis Phase I F8 antibody-IL10 New York, NY www.p zer.com

EP4-R antagonist Eli Lilly osteoarthritis pain Phase I Indianapolis, IN www.lilly.com

FPA008 Five Prime Therapeutics rheumatoid arthritis Phase I (IL-34/CSF1 inhibitor) South San Francisco, CA www. veprime.com

gevokizumab XOMA erosive osteoarthritis of the hand Phase II Berkeley, CA www.xoma.com

GLPG0634 AbbVie rheumatoid arthritis Phase II (JAK1 inhibitor) North Chicago, IL www.abbvie.com Galapagos www.glpg.com Mechelen, Belgium

GSK311739 GlaxoSmithKline rheumatoid arthritis Phase I (macrophage targeted histone Research Triangle Park, NC www.gsk.com deacetylase inhibitor)

GSK3196165 (MOR103) GlaxoSmithKline rheumatoid arthritis Phase II (granulocyte macrophage Research Triangle Park, NC www.gsk.com colony-stimulating factor mAb)

guselkumab Janssen Research & Development rheumatoid arthritis Phase II Raritan, NJ www.janssenrnd.com

Medicines in Development for Older Americans 2014 19 Medicines in Development for Older Americans

Arthritis

Product Name Sponsor Indication Development Phase

ibuprofenamine Tech elds Pharma osteoarthritis Phase II (X0002) Jiangsu, China www.tfpharma.com

INCB47986 Incyte rheumatoid arthritis Phase I (JAK1 inhibitor) Wilmington, DE www.incyte.com

IPI-145 In nity Pharmaceuticals rheumatoid arthritis Phase II (dual PI3K inhibitor) Cambridge, MA www.in .com

JNJ-38518168 Janssen Research & Development active rheumatoid arthritis Phase II (histamine H4 receptor antagonist) Raritan, NJ www.janssenrnd.com

JNJ-40346527 Janssen Research & Development active rheumatoid arthritis Phase II (FMS inhibitor) Raritan, NJ www.janssenrnd.com

KD025 Kadmon rheumatoid arthritis Phase I (ROCK2 inhibitor) New York, NY www.kadmon.com

(L/D)-aminopterin Syntrix Biosystems rheumatoid arthritis Phase II Auburn, WA www.syntrixbio.com

LY3090106 Eli Lilly rheumatoid arthritis Phase I Indianapolis, IN www.lilly.com

mavrilimumab MedImmune rheumatoid arthritis Phase II (anti-GM-CSFR mAb) Gaithersburg, MD www.medimmune.com

mesenchymal stem cell therapy Medipost osteoarthritis Phase I/II for cartilage repair Seoul, South Korea www.medi-post.com

MK-8808 Merck rheumatoid arthritis Phase I completed (rituximab biosimilar) Whitehouse Station, NJ www.merck.com

MORAb-022 Eisai rheumatoid arthritis Phase I (IgG1 mAb) Woodcli Lake, NJ www.eisai.com

NN8210 Novo Nordisk rheumatoid arthritis Phase I (anti-C5aR-215) Plainsboro, NJ www.novonordisk.com

NN8226 Novo Nordisk rheumatoid arthritis Phase II (anti-IL20 antibody) Plainsboro, NJ www.novonordisk.com

Otezla® Celgene rheumatoid arthritis Phase II apremilast Summit, NJ www.celgene.com

PF-04171327 P zer rheumatoid arthritis Phase II (selective glucocorticoid receptor New York, NY www.pfizer.com modulator)

20 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Arthritis

Product Name Sponsor Indication Development Phase

PF-05280586 P zer rheumatoid arthritis Phase I (rituximab biosimilar) New York, NY www.pfizer.com

PF-06410293 P zer rheumatoid arthritis Phase I (adalimumab biosimilar) New York, NY www.pfizer.com

PF-06438179 P zer rheumatoid arthritis Phase I (in iximab biosimilar) New York, NY www.pfizer.com

PRTX-100 Protalex active rheumatoid arthritis Phase I (staphylococcal protein A) Florham Park, NJ www.protalex.com

QAL964 Novartis Pharmaceuticals rheumatoid arthritis Phase II East Hanover, NJ www.novartis.com

Rasuvo™ Medac Pharma rheumatoid arthritis application submitted methotrexate subcutaneous Chicago, IL www.medacpharma.com auto-injection

Ravax™ Immune Response BioPharma rheumatoid arthritis Phase III rheumatoid arthritis vaccine Atlantic City, NJ www.immuneresponsebiopharma. com

SAN-300 Salix Pharmaceuticals rheumatoid arthritis Phase II (VLA-1 mAb) Raleigh, NC www.salix.com

sarilumab Regeneron Pharmaceuticals rheumatoid arthritis Phase III (anti-IL-6R mAb) Tarrytown, NY www.regeneron.com Sano US www.sano .com Bridgewater, NJ

secukinumab Novartis Pharmaceuticals rheumatoid arthritis Phase III (IL-17 inhibitor) East Hanover, NJ (see also diabetes) www.novartis.com

sirukumab Janssen Research & Development rheumatoid arthritis Phase III Raritan, NJ www.janssenrnd.com

SM-04690 Samumed osteoarthritis of the knee Phase I (Wnt pathway modulator) San Diego, CA www.samumed.com

sprifermin EMD Serono osteoarthritis Phase II (FGF-18) Rockland, MA www.emdserono.com

TG-C TissueGene osteoarthritis of the knee Phase II (cell therapy) Rockville, MD www.tissuegene.com

TPX-100 OrthoTrophix osteoarthritis of the knee Phase II (MEPE-derived 23-amino acid Oakland, CA www.orthotrophix.com peptide)

Medicines in Development for Older Americans 2014 21 Medicines in Development for Older Americans

Arthritis

Product Name Sponsor Indication Development Phase

VX-509 Vertex Pharmaceuticals rheumatoid arthritis Phase II (JAK3 inhibitor) Boston, MA www.vrtx.com

XmAb®5871 Xencor moderate to severe rheumatoid Phase II anti-CD19 mAb Monrovia, CA arthritis www.xencor.com Chronic Kidney Disease

Product Name Sponsor Indication Development Phase

atrasentan AbbVie diabetic nephropathy Phase III North Chicago, IL www.abbvie.com

AZD1772//RDX5791 Ardelyx management of uid retention in Phase II (NHE3 inhibitor) Fremont, CA chronic kidney disease and type 2 www.ardelyx.com AstraZeneca diabetes www.astrazeneca.com Wilmington, DE (see also heart disease)

baricitinib Eli Lilly diabetic nephropathy Phase II (JAK1/JAK2 inhibitor) Indianapolis, IN (see also arthritis) www.lilly.com Incyte www.incyte.com Wilmington, DE

BIIB023 Biogen Idec lupus nephritis Phase II (anti-TWEAK mAb) Cambridge, MA www.biogenidec.com

bosutinib P zer autosomal dominant polycystic Phase II (Abl and src-family kinase New York, NY kidney disease www.p zer.com inhibitor)

CCR2/CCR5 chemokine receptor Bristol-Myers Squibb diabetic nephropathy Phase II antagonist Princeton, NJ www.bms.com (BMS-813160)

CCX140 ChemoCentryx diabetic nephropathy Phase II (CCR2 receptor antagonist) Mountain View, CA www.chemocentryx.com

CCX872 ChemoCentryx diabetic nephropathy Phase I (CCR2 receptor antagonist) Mountain View, CA www.chemocentryx.com

CLP-1004 Sorbent Therapeutics removal of excess uid associated Phase I (potassium channel modulator) Sunnyvale, CA with chronic kidney disease www.sorbent.com

CTP-499 Concert Pharmaceuticals diabetic nephropathy Phase II Lexington, MA www.concertpharma.com

22 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Chronic Kidney Disease

Product Name Sponsor Indication Development Phase

nerenone Bayer HealthCare Pharmaceuticals diabetic nephropathy Phase II (MR antagonist) Whippany, NJ (see also heart disease) www.bayerpharma.com

GCS-100 La Jolla Pharmaceutical chronic kidney disease Phase II (galectin inhibitor) San Diego, CA www.ljpc.com

GKT137831 Genkyotex Innovation diabetic nephropathy Phase II Geneva, Switzerland www.genkyotex.com

GS-4977 Gilead Sciences diabetic nephropathy Phase I (ASK-1 inhibitor) Foster City, CA www.gilead.com

H.P. Acthar® Gel Questcor Pharmaceuticals diabetic nephropathy Phase II repository corticotropin injection Anaheim Hills, CA www.questcor.com

Invokana® Janssen Research & Development diabetic neuropathy Phase III canagli ozin Raritan, NJ www.janssenrnd.com

KD020 Kadmon Pharmaceuticals polycystic kidney disease Phase I/II (MTP inhibitor) New York, NY www.kadmon.com

laquinimod Teva Pharmaceutical lupus nephritis Phase II North Wales, PA www.tevapharm.com

LCZ696 Novartis Pharmaceuticals chronic kidney disease Phase III (NEP inhibitor and angiotensin East Hanover, NJ (see also heart disease) www.novartis.com type 1 receptor blocker)

LHW090 Novartis Pharmaceuticals chronic renal insu ciency Phase I East Hanover, NJ www.novartis.com

MT-3995 Mitsubishi Tanabe Pharma diabetic nephropathy Phase I (selective aldosterone receptor Osaka, Japan www.mt-pharma.co.jp antagonist)

NCE therapeutic Eli Lilly chronic kidney disease Phase I Indianapolis, IN www.lilly.com

Neo-Kidney Augment™ Tengion chronic kidney disease in patients Phase I autologous cultured kidney tissue Winston-Salem, NC with type 2 diabetes www.tengion.com cells

PF-00489791 P zer diabetic nephropathy Phase II (PDE5 inhibitor) New York, NY www.pfizer.com

PF-04634817 P zer diabetic nephropathy Phase II (CCR2/5 antagonist) New York, NY www.pfizer.com

Medicines in Development for Older Americans 2014 23 Medicines in Development for Older Americans

Chronic Kidney Disease

Product Name Sponsor Indication Development Phase

pyridoxamine NephroGenex diabetic nephropathy Phase II Research Triangle Park, NC (Fast Track) www.nephrogenex.com

RG7641 Roche kidney disease Phase I Nutley, NJ www.roche.com

TGF-alpha.epiregulin mAb Eli Lilly chronic kidney disease Phase I (LY3016859) Indianapolis, IN www.lilly.com

tolvaptan Otsuka Pharmaceutical autosomal dominant polycystic application submitted Rockville, MD kidney disease (Fast Track) www.otsuka.com

Tradjenta® Boehringer Ingelheim Pharmaceuticals diabetic nephropathy Phase III linagliptin Ridge eld, CT www.boehringer-ingelheim.com Eli Lilly www.lilly.com Indianapolis, IN

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Phase

aclidinium/formoterol Almirall chronic obstructive pulmonary Phase III inhalation Barcelona, Spain disease (COPD) www.frx.com Forest Laboratories New York, NY

AdipoCell™ Bioheart COPD Phase II adipose-derived autologous Sunrise, FL (see also heart disease) www.bioheartinc.com stem cell therapy

ARD-3150 Aradigm non-cystic brosis bronchiectasis Phase III (liposomal cipro oxacin) Hayward, CA www.aradigm.com ORPHAN DRUG

AZD2115 AstraZeneca COPD Phase II (MABA) Wilmington, DE www.astrazeneca.com

AZD4721 AstraZeneca COPD Phase I (CXCR2 antagonist) Wilmington, DE www.astrazeneca.com

AZD7624 AstraZeneca COPD Phase I (inhaled P38 inhibitor) Wilmington, DE www.astrazeneca.com

24 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Phase

BAY 85-8501 Bayer HealthCare Pharmaceuticals bronchiectasis Phase II (neutrophil elastase inhibitor) Whippany, NJ www.bayerpharma.com

BCT197 Novartis Pharmaceuticals COPD Phase II East Hanover, NJ www.novartis.com

benralizumab MedImmune COPD Phase II (anti-IL-5R mAb) Gaithersburg, MD www.medimmune.com

Bronchitol Pharmaxis bronchiectasis Phase III mannitol inhalation Frenchs Forest, Australia www.pharmaxis.com.au ORPHAN DRUG

cipro oxacin dry powder Bayer HealthCare Pharmaceuticals non-cystic brosis bronchiectasis Phase III for inhalation Whippany, NJ www.bayerpharma.com ORPHAN DRUG

CNTO 6785 Janssen Research & Development COPD Phase II (IL-17A modulator) Raritan, NJ (see also arthritis) www.janssenrnd.com

danirixin GlaxoSmithKline COPD Phase I (CXCR2 chemokine receptor Rsch. Triangle Park, NC www.gsk.com antagonist)

erdosteine Alitair Pharmaceuticals bronchitis Phase II Morristown, NJ www.alitair.com

uticasone furoate/vilanterol/ GlaxoSmithKline COPD Phase I umeclidinium Research Triangle Park, NC www.gsk.com Theravance Biopharma U.S. www.theravance.com South San Francisco, CA

GSK2256294 GlaxoSmithKline COPD Phase I (soluble epoxide hydrolase Rsch. Triangle Park, NC www.gsk.com inhibitor)

GSK2269557 GlaxoSmithKline COPD and asthma Phase I (p38 kinase inhibitor) Rsch. Triangle Park, NC www.gsk.com

GSK2793660 GlaxoSmithKline bronchiectasis Phase I (cathepsin C inhibitor) Research Triangle Park, NC www.gsk.com

GSK961081 GlaxoSmithKline COPD Phase II (muscarinic antagonist/ Rsch. Triangle Park, NC www.gsk.com beta2 agonist) Theravance Biopharma U.S. www. theravance.com South San Francisco, CA

Incruse Ellipta GlaxoSmithKline COPD application submitted muscarinic acetylcholine Rsch. Triangle Park, NC www.gsk.com antagonist

Medicines in Development for Older Americans 2014 25 Medicines in Development for Older Americans

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Phase

JNJ-49095397 Janssen Research & Development COPD Phase II (RV568) Raritan, NJ www.janssenrnd.com

losmapimod GlaxoSmithKline COPD Phase II (oral p38 kinase inhibitor) Rsch. Triangle Park, NC www.gsk.com

MEDI8968 MedImmune COPD Phase II (anti-IL-1R mAb) Gaithersburg, MD www.medimmune.com

NVA237 Novartis Pharmaceuticals COPD Phase III (glycopyrrolate inhalation) East Hanover, NJ www.novartis.com

olodaterol Boehringer Ingelheim Pharmaceuticals COPD application submitted Ridge eld, CT www.boehringer-ingelheim.com

olodaterol/tiotropium bromide Boehringer Ingelheim Pharmaceuticals COPD Phase II Ridge eld, CT www.boehringer-ingelheim.com

PF-03715455 P zer COPD Phase I New York, NY www.p zer.com

PH-797804 P zer COPD Phase II (P38 inhibitor) New York, NY www.p zer.com

PT001 Pearl Therapeutics COPD Phase III (glycopyrrolate inhalation aerosol) Redwood City, CA www. pearltherapeutics.com

PT003 Pearl Therapeutics COPD Phase III (glycopyrrolate/formoterol Redwood City, CA www. pearltherapeutics.com inhalation aerosol)

PT010 Pearl Therapeutics COPD Phase I (budesonide, glycopyrronium and Redwood City, CA www. pearltherapeutics.com formoterol inhalation aerosol)

PUR0200 Pulmatrix COPD Phase II (LAMA) Lexington, MA www.pulmatrix.com

PUR118 Pulmatrix COPD Phase I Lexington, MA www. pulmatrix.com

QBM076 Novartis Pharmaceuticals COPD Phase I East Hanover, NJ www.novartis.com

quercetin Quercegen Pharmaceuticals COPD Phase II (thromboxane A2 synthase Sudbury, MA www.quercegen.com inhibitor)

26 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Chronic Obstructive Pulmonary Disease (COPD)

Product Name Sponsor Indication Development Phase

QVA149 Novartis Pharmaceuticals COPD Phase III (glycopyrrolate/indacaterol East Hanover, NJ www.novartis.com inhalation)

SUN-101 Sunovion COPD Phase II (long-acting muscarinic receptor Marlborough, MA www.sunovion.com antagonist)

TD-4208 Theravance Biopharma U.S. COPD Phase II (LAMA) South San Francisco, CA www. theravance.com

TRN-157 Theron Pharmaceuticals COPD Phase I (LAMA) Sunnyvale, CA www.theronpharma.com

vilanterol GlaxoSmithKline COPD Phase III (long-acting beta2 agonist) Rsch. Triangle Park, NC www.gsk.com

Depression

Product Name Sponsor Indication Development Phase

ademetionine MSI Methylation Sciences major depressive disorder Phase II (MSI-195) Burnaby, Canada www.methylationsciences.com

ALKS 5461 Alkermes major depressive disorder Phase III (buprenorphine/samidorphan) Waltham, MA (Fast Track) www.alkermes.com

amitifadine Euthymics Bioscience major depressive disorder Phase II/III (triple reuptake inhibitor) Cambridge, MA www.euthymics.com

armoda nil Teva Pharmaceutical major depressive disorder associated Phase III completed North Wales, PA with bipolar 1 disorder www.tevapharm.com

AVP-786 Avanir Pharmaceuticals treatment-resistant depression Phase I completed (deuterium modi ed Aliso Viejo, CA www.avanir.com dextromethorphan and ultra-low Concert Pharmaceuticals www.concertpharma.com dose quinidine) Lexington, MA

AZD6423 AstraZeneca suicidal ideation Phase I (NMDA modulator) Wilmington, DE www.astrazeneca.com

Botox® Allergan major depressive disorder Phase II onabotulinumtoxinA Irvine, CA www.allergan.com

Medicines in Development for Older Americans 2014 27 Medicines in Development for Older Americans

Depression

Product Name Sponsor Indication Development Phase

brexpiprazole Lundbeck major depressive disorder Phase III (dopamine partial agonist) Deer eld, IL (adjunctive treatment) www.lundbeck.com Otsuka Pharmaceutical (see also Alzheimer’s) www.otsuka.com Rockville, MD

cariprazine Forest Laboratories bipolar depression, major depressive Phase II New York, NY disorder www.frx.com

CERC-301 Cerecor major depressive disorder Phase II (NR2B antagonist) Baltimore, MD (Fast Track) www.cerecor.com ------active suicidal ideation Phase II www.cerecor.com

DSP-1053 Sunovion major depressive disorder Phase I (serotonin uptake inhibitor) Marlborough, MA www.sunovion.com

esketamine Janssen Research & Development treatment-resistant major depressive Phase II (intranasal) Raritan, NJ disorder www.janssenrnd.com (Fast Track)

GLYX-13 Naurex major depressive disorder Phase II Evanston, IL (Fast Track) www.naurex.com

HT-2157 Dart NeuroScience major depressive disorder Phase II (GALR3 antagonist) San Diego, CA www.dartneuroscience.com

JNJ-42847922 Janssen Research & Development major depressive disorder Phase I Raritan, NJ www.janssenrnd.com

Latuda® Sunovion major depressive disorder with mixed Phase III lurasidone Marlborough, MA features www.sunovion.com

LY03005 Luye America Pharmaceuticals major depressive disorder Phase I Princeton, NJ www.luye.cn

LY2940094 Eli Lilly major depressive disorder Phase II (NOC-1 antagonist) Indianapolis, IN www.lilly.com

MIN-117 Minerva Neurosciences major depressive disorder Phase II (5-HT1A/5-HTT receptor Cambridge, MA www.minervaneurosciences.com antagonist)

NRX-1074 Naurex major depressive disorder Phase I (NMDA receptor agonist) Evanston, IL www.naurex.com

NSI-189 Neuralstem major depressive disorder Phase I (stimulating neurogenesis) Germantown, MD www.neuralstem.com

28 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Depression

Product Name Sponsor Indication Development Phase

RG1578 Roche major depressive disorder Phase II (mGluR2) Nutley, NJ www.roche.com

RG7090 Roche treatment-resistant depression Phase II (mGluR5 antagonist) Nutley, NJ www.roche.com

RO4995819 Roche major depressive disorder Phase II Nutley, NJ www.roche.com

Rozerem® Takeda Pharmaceutical acute depressive episodes associated Phase III ramelteon Deer eld, IL with bipolar 1 disorder www.takeda.com (sublingual formulation)

SEP-363856 Sunovion major depressive disorder Phase I Marlborough, MA www.sunovion.com

tedatioxetine Lundbeck major depressive disorder Phase II Deer eld, IL www.lundbeck.com Takeda Pharmaceutical www.takeda.com Deer eld, IL Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

Afrezza® MannKind type 1 diabetes, type 2 diabetes application submitted insulin inhalation Valencia, CA www.mannkindcorp.com

alpha-1 antitrypsin (AAT) Omni Bio Pharmaceutical type 1 diabetes Phase I/II (serine proteinase inhibitor) Greenwood Village, CO www.omnibiopharma.com

AMG 876 Amgen type 2 diabetes Phase I (fusion protein) Thousand Oaks, CA www.amgen.com

analog insulin-PH20 Halozyme Therapeutics type 1 diabetes , type 2 diabetes Phase II San Diego, CA www.halozyme.com

BI-187004 CL Boehringer Ingelheim Pharmaceuticals type 2 diabetes Phase I Ridge eld, CT www.boehringer-ingelheim.com

BIOD-123 Biodel type 1 diabetes Phase II (RHI-based ultra-rapid-acting Danbury, CT www.biodel.com insulin)

Medicines in Development for Older Americans 2014 29 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

BIOD-531 Biodel type 2 diabetes Phase I (RHI-based concentrated Danbury, CT www.biodel.com ultra-rapid-acting insulin)

BTI320 Boston Therapeutics type 2 diabetes Phase II Manchester, NH www.bostonti.com

Bydureon® AstraZeneca type 2 diabetes Phase III exenatide weekly suspension Wilmington, DE www.astrazeneca.com

canagli ozin/metformin Janssen Research & Development type 2 diabetes Phase III extended-release xed-dose Raritan, NJ www.janssenrnd.com combination

canagli ozin/metformin Janssen Research & Development type 2 diabetes application submitted immediate-release xed-dose Raritan, NJ www.janssenrnd.com combination

CJC-1134-PC ConjuChem type 2 diabetes Phase II (GLP-1 stimulant) Los Angeles, CA www.conjuchem.com

dapagli ozin/saxagliptin AstraZeneca diabetes Phase III xed-dose combination Wilmington, DE www.astrazeneca.com

diabetes biologic Eli Lilly diabetes Phase I Indianapolis, IN www.lilly.com

diabetes NCE Eli Lilly diabetes Phase I Indianapolis, IN www.lilly.com

DS-1150b Daiichi Sankyo type 2 diabetes Phase I completed (GLUT4 stimulant) Parsippany, NJ www.daiichisankyo.com

DS-7309 Daiichi Sankyo type 2 diabetes Phase I (glucokinase activator) Parsippany, NJ www.daiichisankyo.com

DS-8500 Daiichi Sankyo diabetes Phase I (GPR119 agonist) Parsippany, NJ www.daiichisankyo.com

30 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

dulaglutide Eli Lilly type 2 diabetes application submitted (GLP-1 agonist) Indianapolis, IN www.lilly.com

DV-0100 DiaVacs type 1 diabetes Phase II (dendritic cell vaccine) Edgewater, NJ www.diavacs.us.com ORPHAN DRUG

EGT 0001442 Theracos type 2 diabetes Phase II (SGLT2 inhibitor) Marlborough, MA www.theracos.com

eicosapentaenoic acid/metformin Thetis Pharmaceuticals type 2 diabetes Phase I xed-dose combination Southport, CT (see also heart disease) www.thetispharma.com (TP-101)

empagli ozin Boehringer Ingelheim Pharmaceuticals type 2 diabetes application submitted (SGLT2 inhibitor) Ridge eld, CT www.boehringer-ingelheim.com Eli Lilly www.lilly.com Indianapolis, IN

empagli ozin/linagliptin Boehringer Ingelheim Pharmaceuticals type 2 diabetes application submitted xed-dose combination Ridge eld, CT www.boehringer-ingelheim.com Eli Lilly www.lilly.com Indianapolis, IN

empagli ozin/metformin Boehringer Ingelheim Pharmaceuticals type 2 diabetes Phase I xed-dose combination Ridge eld, CT www.boehringer-ingelheim.com Eli Lilly www.lilly.com Indianapolis, IN

ertugli ozin Merck type 2 diabetes Phase III (SGLT2 inhibitor) Whitehouse Station, NJ www.merck.com P zer www.pfizer.com New York, NY

glucagon-R antagonist Eli Lilly type 2 diabetes Phase II (LY2409021) Indianapolis, IN www.lilly.com

GSK2330672 GlaxoSmithKline type 2 diabetes Phase II (iBAT inhibitor) Research Triangle Park, NC www.gsk.com

HE3286 Harbor Biosciences type 2 diabetes Phase II San Diego, CA www.harbortx.com

HIP-2B CureDM type 1 diabetes, type 2 diabetes Phase I (human pro-islet peptide) Wilmington, DE www.curedm.com

HM11260C Hanmi Pharmaceutical type 2 diabetes Phase II (exenatide long-acting) Seoul, South Korea www.hanmipharm.com

Medicines in Development for Older Americans 2014 31 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

HM12460A Hanmi Pharmaceutical type 1 diabetes, type 2 diabetes Phase I (long-acting insulin) Seoul, South Korea www.hanmipharm.com

insulin aspart faster-acting Novo Nordisk type 1 diabetes, type 2 diabetes Phase III (NN1218) Plainsboro, NJ www.novonordisk.com

insulin biosimilar Harvest Moon Pharmaceuticals diabetes Phase III Falls Church, VA www.harvestmoonpharma.com

insulin biosimilar Sano US diabetes Phase I Bridgewater, NJ www.sanofi.com

insulin glargine biosimilar Harvest Moon Pharmaceuticals diabetes in clinical trials Falls Church, VA www.harvestmoonpharma.com

insulin glargine biosimilar Wockhardt type 1 diabetes Phase I completed Mumbai, India www.wockhardt.com

insulin lispro Eli Lilly type 1 diabetes, type 2 diabetes in clinical trials (LY275585) Indianapolis, IN www.lilly.com

insulin peglispro Eli Lilly type 1 diabetes, type 2 diabetes Phase III (LY2605541) Indianapolis, IN www.lilly.com

ISIS-GCCRRx Isis Pharmaceuticals type 2 diabetes Phase II (antisense oligonucleotide) Carlsbad, CA www.isispharm.com

ISIS-GCGRRx Isis Pharmaceuticals type 2 diabetes Phase II (antisense oligonucleotide) Carlsbad, CA www.isispharm.com

ISIS-PTP1BRx Isis Pharmaceuticals type 2 diabetes Phase II (antisense oligonucleotide) Carlsbad, CA www.isispharm.com

ITCA 650 Intarcia Therapeutics type 2 diabetes Phase III (exenatide subcutaneous implant) Boston, MA www.intarcia.com

JTT-251 Akros Pharma type 2 diabetes Phase I Princeton, NJ www.akrospharma.com

JTT-252 Akros Pharma type 2 diabetes Phase I Princeton, NJ www.akrospharma.com

JTT-851 Akros Pharma type 2 diabetes Phase II (G protein-coupled receptor 40 Princeton, NJ www.akrospharma.com agonist)

KD026 Kadmon Pharmaceuticals type 2 diabetes Phase II (MTP inhibitor) New York, NY www.kadmon.com

32 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

LAI287 Novo Nordisk type 1 diabetes, type 2 diabetes Phase I (NN1436) Plainsboro, NJ www.novonordisk.com

LGD-6972 Ligand Pharmaceuticals type 2 diabetes Phase I (glucagon receptor antagonist) La Jolla, CA www.ligand.com

LIK066 Novartis Pharmaceuticals type 2 diabetes Phase II (SGLT 1/2 inhibitor) East Hanover, NJ www.novartis.com

linagliptin/pioglitazone Boehringer Ingelheim Pharmaceuticals type 2 diabetes Phase III completed xed-dose combination Ridge eld, CT www.boehringer-ingelheim.com Eli Lilly www.lilly.com Indianapolis, IN

LixiLan Sano US type 2 diabetes Phase III lixisenatide/insulin glargine Bridgewater, NJ www.sanofi.com xed ratio

luseogli ozin Taisho Pharmaceutical type 2 diabetes Phase I (TS-071) Tokyo, Japan www.taisho.co.jp

LX4211 Lexicon Pharmaceuticals type 1 diabetes, type 2 diabetes Phase II (SGLT1/SGLT2 inhibitor) The Woodlands, TX www.lexgen.com

Lyxumia® Sano US type 2 diabetes Phase III lixisenatide Bridgewater, NJ www.sanofi.com

MBX-2982 CymaBay Therapeutics type 2 diabetes Phase II Hayward, CA www.cymabay.com

mesenchymal precursor cells Mesoblast type 2 diabetes Phase II (MPC) Melbourne, Australia www.mesoblast.com

MK-1293 Merck type 1 diabetes, type 2 diabetes Phase III (insulin glargine biosimilar) Whitehouse Station, NJ www.merck.com

MK-8521 Merck type 2 diabetes Phase I Whitehouse Station, NJ www.merck.com

MK-8666 Merck type 2 diabetes Phase I Whitehouse Station, NJ www.merck.com

MSDC-0602 Metabolic Solutions Development type 2 diabetes Phase II (mTOT modulator) Kalamazoo, MI www.msdrx.com

new insulin glargine biosimilar Boehringer Ingelheim Pharmaceuticals type 1 diabetes, type 2 diabetes application submitted (LY2963016) Ridge eld, CT www.boehringer-ingelheim.com Eli Lilly www.lilly.com Indianapolis, IN

Medicines in Development for Older Americans 2014 33 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

NewMet™ Elcelyx Therapeutics type 2 diabetes Phase II metformin delayed release San Diego, CA www.elcelyx.com

NGM 282 NGM Biopharmaceuticals type 2 diabetes Phase II South San Francisco, CA www.ngmbio.com

NM504 MicroBiome Therapeutics metformin-intolerant type 2 diabetes Phase 0 (microbiome modulator) Broom eld, CO www.mbiome.com

NN1953 Novo Nordisk type 1 diabetes, type 2 diabetes Phase I (oral insulin) Plainsboro, NJ www.novonordisk.com

NN9924 Novo Nordisk type 2 diabetes Phase II Plainsboro, NJ www.novonordisk.com

NN9926 Novo Nordisk type 2 diabetes Phase I Plainsboro, NJ www.novonordisk.com

NN9927 Novo Nordisk type 2 diabetes Phase I Plainsboro, NJ www.novonordisk.com

NN9928 Novo Nordisk type 2 diabetes Phase I Plainsboro, NJ www.novonordisk.com

omarigliptin Merck type 2 diabetes Phase III (DPP-4 inhibitor) Whitehouse Station, NJ www.merck.com

Oral-Lyn® Generex Biotechnology type 1 diabetes Phase III oral insulin Toronto, Canada www.generex.com

ORMD 0801 Oramed type 1 diabetes, type 2 diabetes Phase II (oral insulin capsule) Jerusalem, Israel www.oramed.com

oxyntomodulin peptide Eli Lilly diabetes Phase I Indianapolis, IN www.lilly.com

P7435 Piramal Enterprises diabetes Phase I Mumbai, India www.piramal.com

P11187 Piramal Enterprises type 2 diabetes Phase I Mumbai, India www.piramal.com

PB1023 PhaseBio Pharmaceuticals type 2 diabetes Phase II (weekly GLP-1R agonist) Malvern, PA www.phasebio.com

PE0139 PhaseBio Pharmaceuticals type 2 diabetes Phase I (basal native insulin) Malvern, PA www.phasebio.com

34 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

PEG-FGF21 Ambrx type 2 diabetes Phase I (BMS-986036) San Diego, CA www.ambrx.com Bristol-Myers Squibb www.bms.com Princeton, NJ

Peptide p277 Andromeda Biotech type 1 diabetes Phase III ORPHAN DRUG Yavne, Israel www.andromedabio.com

PF-04937319 P zer type 2 diabetes Phase II (partial glucokinase activator) New York, NY www.pfizer.com

PF-05175157 P zer type 2 diabetes Phase II (acetyl-CoA carboxylase inhibitor) New York, NY www.pfizer.com

PF-06291874 P zer type 2 diabetes Phase I New York, NY www.pfizer.com

PF-06342674 P zer type 1 diabetes Phase I New York, NY www.pfizer.com

ranolazine extended release Gilead Sciences type 2 diabetes Phase III Foster City, CA www.gilead.com

remogli ozin-etabonate BHV Pharma type 2 diabetes Phase II (SGLT2 inhibitor) Research Triangle Park, NC www.bhvpharma.com

RG7697 Roche type 2 diabetes Phase I (dual agonist [GLP and GIP] Nutley, NJ www.roche.com peptide analogue)

RM 493 Rhythm Pharmaceuticals diabetes Phase II (MC4R peptide therapeutic) Boston, MA www.rhythmtx.com

Ryzodeq® Novo Nordisk type 1 diabetes, type 2 diabetes application submitted insulin degludec/insulin aspart Plainsboro, NJ www.novonordisk.com

S-707106 Shionogi type 2 diabetes Phase II (insulin sensitizer) Florham Park, NJ www.shionogi.com

secukinumab Novartis Pharmaceuticals type 1 diabetes Phase I (IL-17 inhibitor) East Hanover, NJ (see also arthritis) www.novartis.com

semaglutide Novo Nordisk type 2 diabetes Phase III (NN9535) Plainsboro, NJ www.novonordisk.com

teneligliptin Mitsubishi Tanabe Pharma America type 2 diabetes Phase I (DPP-4 inhibitor) Jersey City, NJ www.mt-pharma-america.com

Medicines in Development for Older Americans 2014 35 Medicines in Development for Older Americans

Diabetes, Type 1 and Type 2 Diabetes

Product Name Sponsor Indication Development Phase

teplizumab Macrogenics type 1 diabetes Phase III (anti-CD3 mAb) Rockville, MD www.macrogenics.com ORPHAN DRUG

TOL-3021 Tolerion type 1 diabetes Phase II (antigen-speci c Portola Valley, CA www.tolerioninc.com immunotherapeutic vaccine)

trelagliptin Takeda Pharmaceuticals type 2 diabetes Phase II (DPP-4 inhibitor) Deer eld, IL www.takeda.com

Tresiba® Novo Nordisk type 1 diabetes, type 2 diabetes application submitted insulin degludec Plainsboro, NJ www.novonordisk.com

TRI-102 Tris Pharma type 2 diabetes in clinical trials Monmouth Junction, NJ www.trispharma.com

TTP054 TransTech Pharma type 2 diabetes Phase II (GLP-1 receptor agonist) High Point, NC www.ttpharma.com

TTP399 TransTech Pharma type 2 diabetes Phase I/II (glucokinase inhibitor) High Point, NC www.ttpharma.com

TTP814 TransTech Pharma type 2 diabetes Phase I/II (PTP-1B inhibitor) High Point, NC www.ttpharma.com

U300 Sano US type 1 diabetes, type 2 diabetes Phase III (insulin glargine) Bridgewater, NJ www.sanofi.com

U-Strip™ Transdermal Specialties type 1 diabetes, type 2 diabetes Phase I insulin transdermal ultrasonic Norwalk, CT www.transdermalspecialties.com patch

Victoza® Novo Nordisk type 1 diabetes Phase III liraglutide Plainsboro, NJ www.novonordisk.com

VK0612 Viking Therapeutics type 2 diabetes Phase II (FBPase inhibitor) La Jolla, CA www.vikingtherapeutics.com

Xigduo™ XR FDC AstraZeneca type 2 diabetes application submitted dapagli ozin/metformin Wilmington, DE www.astrazeneca.com xed-dose combination

Xultophy® Novo Nordisk type 2 diabetes Phase III insulin degludec/liraglutide Plainsboro, NJ www.novonordisk.com (NN9068)

36 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Glaucoma

Product Name Sponsor Indication Development Phase

AC 262271 ACADIA Pharmaceuticals glaucoma Phase I (muscarinic receptor agonist) San Diego, CA www.acadia-pharm.com Allergan www.allergan.com Irvine, CA

AMA0076 Amakem glaucoma Phase II (ROCK inhibitor) Diepenbeek, Belgium www.amakem.com

bimatoprost sustained release Allergan glaucoma Phase II Irvine, CA www.allergan.com

bimatoprost/brimonidine Allergan glaucoma Phase II completed xed-dose combination Irvine, CA www.allergan.com

brinzolamide/timolol Alcon glaucoma Phase III completed xed-dose combination Fort Worth, TX www.alcon.com

CF101 Can-Fite Pharma glaucoma Phase II (adenosine A3 receptor agonist) Petah-Tikva, Israel (see also arthritis) www.ophthalix.com OphthaliX Carson City, NV

DE-117 Santen Pharmaceutical glaucoma Phase II (EP2 receptor agonist) Emeryville, CA www.santeninc.com

dorzolamide/latanoprost Alleanza Pharmaceuticals glaucoma Phase II completed xed-dose combination Tampa, FL

latanoprost punctal plug Mati Therapeutics glaucoma Phase II Austin, TX www.matitherapeutics.com

latanoprost sustained released P zer glaucoma Phase I/II (bioerodible) New York, NY www.p zer.com pSivida www.psivida.com Watertown, MA

latanoprostene bunod Bausch & Lomb glaucoma Phase III Rochester, NY www.bausch.com

ONO-9054 Ono Pharmaceutical open-angle glaucoma Phase I (prostaglandin FP/EP3 receptor Osaka, Japan www.ono.co.jp agonist)

OPA-6566 Acucela glaucoma Phase I/II (adenosine A2A receptor agonist) Seattle, WA www.acucela.com Otsuka Pharmaceutical Tokyo, Japan

Medicines in Development for Older Americans 2014 37 Medicines in Development for Older Americans

Glaucoma

Product Name Sponsor Indication Development Phase

QPI-1007 Quark Pharmaceuticals angle-closure glaucoma Phase II (RNA interference) Fremont, CA www.quarkpharma.com

Rhopressa™ Aerie Pharmaceuticals glaucoma Phase II ROCK/NET inhibitor Bedminster, NJ www.aeriepharma.com

Roclatan™ Aerie Pharmaceuticals glaucoma Phase II ROCK/NET inhibitor and latanaprost Bedminster, NJ www.aeriepharma.com

trabodenoson Inotek Pharmaceuticals glaucoma Phase II Lexington, MA www.inotekcorp.com

travoprost punctal plug Ocular Therapeutix glaucoma Phase II Bedford, MA www.ocutx.com

VISION 5 ForSight Vision5 glaucoma Phase II (timolol insert) Menlo Park, CA www.forsightvision5.com

Heart Disease

Product Name Sponsor Indication Development Phase

AdipoCell™ Bioheart heart failure Phase I/II adipose-derived autologous Sunrise, FL (see also COPD) www.bioheartinc.com stem cell therapy

AEM-28 LipimetiX Development hyperlipidemia Phase I Natick, MA www.lipimetix.com

alirocumab Regeneron Pharmaceuticals hypercholesterolemia Phase III (anti-PCSK-9 mAb) Tarrytown, NY www.regeneron.com Sano US www.sano .com Bridgewater, NJ

amlodipine/telmisartan/ Boehringer Ingelheim Pharmaceuticals hypertension Phase I hydrochlorothiazide Ridge eld, CT www.boehringer-ingelheim.com xed-dose combination

AMR102 Amarin hyperlipidemia Phase I completed (ethyl eicosapentaenoic acid/rosu- Bedminster, NJ www.amarincorp.com vastatin xed-dose combination)

anacetrapib Merck atherosclerosis, hypercholesterolemia Phase III (MK-0859) Whitehouse Station, NJ www.merck.com

ANX-042 Anexon heart failure Phase I completed (natriuretic peptide) Cambridge, MA

38 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Heart Disease

Product Name Sponsor Indication Development Phase

AZD1772/RDX5791 Ardelyx heart failure Phase II (NHE3 inhibitor) Fremont, CA (see also chronic kidney disease) www.ardelyx.com AstraZenenca www.astrazeneca.com Wilmington, DE

BAY 98-07106 Bayer HealthCare Pharmaceuticals essential hypertension Phase III (candesartan cilexetil/nifedipine Whippany, NJ www.bayerpharma.com xed-dose combination)

BAY 10-67197 Bayer HealthCare Pharmaceuticals heart failure Phase II (partial adenosine A1 agonist) Whippany, NJ www.bayerpharma.com

BAY 11-42524 Bayer HealthCare Pharmaceuticals heart failure Phase I (chymase inhibitor) Whippany, NJ www.bayerpharma.com

Bendavia™ Stealth Peptides chronic heart failure Phase I mitochondrial permeability Newton, MA www.stealthpeptides.com transition pore inhibitor

bococizumab P zer hyperlipidemia Phase III (PCSK9 inhibitor) New York, NY www.p zer.com

bucindolol ARCA biopharma atrial brillation Phase II/III Westminster, CO www.arcabiopharma.com

C3BS-CQR-1 Cardio3 Biosciences chronic heart failure Phase III Mont-Saint-Guibert, Belgium www.c3bs.com

CEP-41750 Teva Pharmaceutical chronic heart failure Phase III (mesenchymal precursor cells) North Wales, PA www.tevapharm.com

CLP-1001 Sorbent Therapeutics chronic heart failure Phase II (sodium-potassium-chloride Sunnyvale, CA www.sorbent.com symporter inhibitor)

Collategene® AnGes ischemic heart disease Phase I DNA plasmid with hepatocyte Bethesda, MD www.anges-mg.com growth factor gene

CT-2003 Catabasis Pharmaceuticals refractory severe hypertriglyceridemia Phase II (eicosapentaenoic acid/niacin) Cambridge, MA www.catabasis.com

CXL-1427 Cardioxyl Pharmaceuticals acute decompensated heart failure Phase I (NHO donor therapeutic) Chapel Hill, NC www.cardioxyl.com

dronedarone/ranolazine Gilead Sciences paroxysmal atrial brillation Phase II xed-dose combination Foster City, CA www.gilead.com (late sodium current inhibitor)

Medicines in Development for Older Americans 2014 39 Medicines in Development for Older Americans

Heart Disease

Product Name Sponsor Indication Development Phase

eicosapentaenoic acid/metformin Thetis Pharmaceuticals hypertriglyceridemia Phase I xed-dose combination Southport, CT (see also diabetes) www.thetispharma.com (TP101)

ETC-1002 Esperion Therapeutics hypercholesterolemia Phase II (ATP inhibitor/AMPK stimulator) Ann Arbor, MI www.esperion.com

evolocumab Amgen hypercholesterolemia Phase III (PCSK9 protein inhibitor) Thousand Oaks, CA www.amgen.com

febuxostat Takeda Pharmaceuticals hypertension Phase II Deer eld, IL www.takeda.com

nerenone Bayer HealthCare Pharmaceuticals chronic heart failure Phase II (MR antagonist) Whippany, NJ (see also chronic kidney disease) www.bayerpharma.com

GS-6615 Gilead Sciences ventricular tachycardiaventricular Phase I (late sodium current inhibitor) Foster City, CA brillation www.gilead.com

HL040 HanAll Biopharma hyperlipidemia, hypertension Phase II (atorvastatin/losartan Seoul, Korea www.hanall.co.kr xed-dose combination)

HS-25 Zhejiang Hisun Pharmaceutical hypercholesterolemia Phase II Zhejiang, China www.hisunusa.com

hypertension NCE Eli Lilly hypertension Phase I Indianapolis, IN www.lilly.com

ISIS-APOARx Isis Pharmaceuticals hyperlipoproteinemias Phase I (antisense oligonucleotide) Carlsbad, CA www.isispharm.com

ISIS-APOCIIIRx Isis Pharmaceuticals hypertriglyceridemia Phase I (antisense oligonucleotide) Carlsbad, CA www.isispharm.com

Kynamro® Genzyme severe hyperlipoproteinemia type II Phase III mipomersen Cambridge, MA www.genzyme.com

LCZ696 Novartis Pharmaceuticals heart failure Phase III (NEP inhibitor and angiotensin East Hanover, NJ (reduced ejection fraction) www.novartis.com type 1 receptor blocker) (see also chronic kidney disease) ------heart failure Phase III (preserved ejection fraction) www.novartis.com

LFF269 Novartis Pharmaceuticals essential hypertension Phase II East Hanover, NJ www.novartis.com

40 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

Heart Disease

Product Name Sponsor Indication Development Phase

LMI 1195 Lantheus Medical Imaging heart failure (diagnosis) Phase I (cardiac neuronal agent) N. Billerica, MA www.lantheus.com

LY3015014 Eli Lilly hypercholesterolemia Phase II (PCSK9 mAb) Indianapolis, IN www.lilly.com

MGL-3196 Madrigal Pharmaceuticals dyslipidemia, hypercholesterolemia Phase I (thyroid hormone receptor beta Fort Washington, PA www.madrigalpharma.com agonist)

MyoCell® Bioheart severe heart damage in heart failure Phase II/III autologous muscle stem cell Sunrise, FL www.bioheartinc.com therapy

nebivolol/valsartan Forest Laboratories hypertension application submitted New York, NY www.frx.com

omecamtiv mecarbil Amgen heart failure Phase II Thousand Oaks, CA www.amgen.com Cytokinetics www.cytokinetics.com South San Francisco, CA

ONO-4232 Ono Pharma USA acute heart failure Phase I (prostaglandin E EP4 receptor Trenton, NJ www.ono.co.jp agonist)

OPC 108459 Otsuka America Pharmaceutical paroxysmal and persistent atrial Phase I Rockville, MD brillation www.otsuka.com

perindopril/amlodipine Symplmed Pharmaceutical hypertension Phase III xed-dose combination Cincinnati, OH www.symplmed.com

PF-06678552 P zer hyperlipidemia Phase I New York, NY www.p zer.com

PRC-4016 Pronova BioPharma dyslipidemia, hypertriglyceridemia Phase II Lysaker, Norway www.basf.com

recombinant human Zensun USA chronic heart failure Phase II neuregulin-1 beta San Diego, CA www.zensunusa.com

recombinant neuregulin-1 (GGF-2) Acorda Therapeutics heart failure Phase I Ardsley, NY www.acorda.com

RG7652 Genentech hyperlipidemia Phase II (PCSK9 inhibitor) South San Francisco, CA www.gene.com

Medicines in Development for Older Americans 2014 41 Medicines in Development for Older Americans

Heart Disease

Product Name Sponsor Indication Development Phase

SERCA-2a gene therapy Celladon heart failure Phase II San Diego, CA (Breakthrough Therapy) (Fast Track) www.celladon.com

serelaxin Novartis Pharmaceuticals acute heart failure application submitted East Hanover, NJ (Breakthrough Therapy) (Fast Track) www.novartis.com ------chronic heart failure Phase II www.novartis.com

sirolimus-eluting coronary stent Svelte Medical Systems ischemic heart disorder Phase II New Providence, NJ www.sveltemedical.com

Tekturna® Novartis Pharmaceuticals reduction of cardiovascular death and Phase III aliskiren East Hanover, NJ hospitalization in chronic heart failure www.novartis.com

TRV027 Forest Laboratories acute heart failure Phase II New York, NY www.frx.com Trevena www.trevenainc.com King of Prussia, PA

ularitide Cardiorentis acute heart failure Phase III Zug, Switzerland www.cardiorentis.com

vanoxerine ChanRx atrial brillation Phase II Cleveland, OH www.chanrx.com

Vasomera™ PhaseBio Pharmaceuticals essential hypertension Phase I completed vasoactive intestinal peptide Malvern, PA www.phasebio.com type II receptor agonist

vasopressin receptor antagonist Bayer HealthCare Pharmaceutical heart failure Phase I Whippany, NJ www.bayerpharma.com

vericigiuat Bayer HealthCare Pharmaceutical worsening chronic heart failure Phase II (sGC stimulator) Whippany, NJ www.bayerpharma.com

Xarelto® Bayer HealthCare Pharmaceutical chronic heart failure Phase III rivaroxaban Whippany, NJ www.bayerpharma.com Janssen Research & Development www.janssenrnd.com Raritan, NJ

XZK Luye Pharmaceutical hyperlipidemia Phase II (Chinese red yeast rice extract) Shandong, China www.wpu.com/cn/en Beijing Peking University WBL Biotech Beijing, China

42 Medicines in Development for Older Americans 2014 Medicines in Development for Older Americans

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 June 4, 2014. The medicines in this report include medicines being developed by U.S.-based companies conducting trials in the United States and abroad, PhRMA-member companies conducting trials in the United States and abroad, and foreign companies conducting clinical trials in the United States. The information in this report may not be comprehensive. For more speciﬁ c 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 website. A publication of PhRMA’s Communications & Public Affairs Department (202) 835-3460 www.phrma.org | www.innovation.org | www.pparx.org Provided as a public service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2014 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given.

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Medicines in Development for Older Americans 2014 43 Glossary

Alzheimer’s disease—The most com- cognitive disorders—Disorders of the last for 2 years. People with depressive mon form of dementia, characterized by higher mental processes—including illnesses do not all experience the same progressive and chronic deterioration of understanding, reasoning, knowledge, symptoms. The severity, frequency, and cognitive functions, including memory, and intellectual capacity. A person with duration of symptoms vary depending thinking and reasoning. Early manifesta- a cognitive disorder, such as Alzheimer’s on the individual and his or her particu- tions include forgetfulness, impaired abil- disease, does not process information lar illness. A few of the many signs and ity to focus, and changes in mood and correctly within the brain, resulting in symptoms of depression are: persis- personality. As the disease progresses, impaired awareness and judgment, dif- tent sad, anxious, or “empty” feelings; there is a loss of computational ability, fi culty reasoning and focusing, loss of feelings of hopelessness or pessimism; in addition to word-fi nding problems memory and abnormal mental capacity. fatigue and decreased energy; diffi culty and diffi culty with ordinary activities. People with cognitive disorders have concentrating, remembering details, and Ultimately, the disease leads to severe problems acquiring, mentally organizing making decisions; overeating, or appetite memory loss, complete disorientation, and responding to information, which loss; and thoughts of suicide, or suicide social withdrawal, loss of independence, results in an inability to function normally attempts. and death. in everyday life situations. diabetes—A chronic disease in which the anemia—A condition in which the dementia—The loss of mental ability body does not produce or properly use number of red blood cells or amount that interferes with normal daily activi- insulin, a hormone that is needed to con- of hemoglobin (the protein that carries ties. It lasts more than six months, is not vert sugar, starches and other food into oxygen within the body or blood stream) present at birth and is not associated energy needed for daily life. Symptoms is below normal. with loss or altered consciousness. The may include excessive thirst, hunger, natural decline of these functions with urination and weight loss. The cause application submitted—An application age is grossly exaggerated in dementia. of diabetes continues to be a mystery, for marketing has been submitted to although both genetics and environ- the U.S. Food and Drug Administration depression—Everyone occasionally feels mental factors such as obesity and lack (FDA). The application can either be an blue or sad, but those feelings are usu- of exercise appear to play roles. Type 1 NDA (new drug application) or a BLA ally short-lived and pass within a couple diabetes results from the body’s failure (biologic license application). of days. Depression, however, interferes to produce insulin, which “unlocks” the with daily life and causes pain for both atrial fi brillation—Very fast electri- cells of the body, allowing glucose to en- the sufferers and those who care about ter and fuel them. It is estimated that 5 cal discharge patterns that make the them. Depression is a common but seri- heart’s atria contract extremely rapidly, percent to 10 percent of Americans who ous illness. Major depression and persis- are diagnosed with diabetes have type 1, which causes the ventricles to contract tent depressive disorder are among the faster and less effi ciently than normal. which requires insulin treatment. Type 2 several forms of depressive disorders. diabetes results from insulin resistance (a As a result, inadequate amounts of Major depression causes severe symp- blood are pumped out of the heart, condition in which the body fails to prop- toms that interfere with a person’s ability erly use insulin), combined with relative blood pressure falls, and heart failure to work, sleep, study, eat, and enjoy life. may occur. insulin defi ciency. Most Americans who An episode can occur only once in a per- are diagnosed with diabetes have type 2, chronic obstructive pulmonary disease son’s lifetime, but more often, a person which in most cases can be controlled (COPD)—A group of lung diseases, has several episodes. Persistent depres- including chronic bronchitis and em- sive disorder causes a depressed mood Phase 0—First-in-human trials con- physema, in which there is a persistent that lasts for at least 2 years. A person ducted in accordance with FDA’s 2006 disruption of airfl ow out of the lungs and diagnosed with persistent depressive guidance on exploratory Investigational eventual hypoxemia (low level of oxygen disorder may have episodes of major New Drug (IND) studies designed to in the blood). depression along with periods of less speed development of promising drugs severe symptoms, but symptoms must by establishing early whether the tested

44 Medicines in Development for Older Americans 2014 Glossary

if treated properly by a combination of glaucoma—An eye disease associated ischemia—Insuffi cient supply of blood to dietary measures, weight loss, and oral with increased pressure within the eye- an organ or tissue, which can cause or- medication. ball. If untreated, it may lead to perma- gan damage such as an ischemic stroke. nent and complete blindness. diabetic nephropathy—Damage or mild Alzheimer’s disease—A stage of disease to the kidney that can occur in heart failure—The end result of many Alzheimer’s disease characterized by a people with diabetes. The kidneys have different types of heart disease. The series of changes in cognitive abilities many tiny blood vessels that fi lter waste heart cannot pump blood out normally. that may include memory loss for recent from the blood. High blood sugar from This results in congestion (water and salt events, diffi culty with problem solving, diabetes can destroy those blood ves- retention) in the lungs, swelling in the changes in personality, diffi culty orga- sels. Overtime, the kidney isn’t able to extremities, and reduced blood fl ow to nizing and expressing thoughts, getting do its job as well and may stop working body tissues. lost or misplacing belongings. This is the completely, which is called kidney failure. stage at which the disease is often fi rst hyperlipidemia—A group of metabolic diagnosed. Fast Track—A process designed to facili- disorders characterized by high levels of tate the development and expedite the lipids (fatty substances, including choles- moderate Alzheimer’s disease—A stage review of drugs to treat serious diseases terol) in the blood. Hyperlipidemia is a of Alzheimer’s disease characterized by and fi ll an unmet medical need. The risk factor for accelerated atherosclerosis increased confusion, greater memory status is assigned by the U.S. Food and and premature heart attacks. loss, signifi cant changes in personal- Drug Administration (FDA). The purpose ity, and the need for assistance with — of this process is to get important new hypertension (high blood pressure) basic daily activities. These changes are Persistent elevation of blood pressure drugs to the patient earlier. Fast Track related to damage in areas of the brain above the normal range while the heart addresses a broad range of serious dis- that control language, reasoning, sensory is in systolic (contracting) or diastolic eases. In general, determining factors for processing, and conscious thinking. At (relaxed) mode. Uncontrolled, chronic whether a drug receives Fast Track in- this stage, patients may have problems hypertension strains the heart, damages clude whether the drug will affect factors recognizing family and friends, experi- arteries and creates a greater risk of such as survival, day-to-day function- ence hallucinations, delusions, and para- heart attack, stroke and kidney problems. ing, or the likelihood that the disease, if noia, and may behave impulsively. left untreated, will progress from a less hypertriglyceridemia—An elevated tri- —A drug to treat a dis- severe condition to a more serious one. Orphan Drug glyceride concentration in the blood. ease that has a patient population of Filling an unmet medical need is defi ned 200,000 or less in the United States, or as providing a therapy where none ex- Hypothyroidism—Also known as an un- a disease that has a patient population ists or providing a therapy that may be deractive thyroid, is a condition where of more than 200,000 and a develop- potentially superior to existing therapy. the thyroid gland doesn’t produce ment cost that will not be recovered Once a drug receives Fast Track designa- enough of certain important hormones. from sales in the United States. tion, early and frequent communication Women, especially those older than age 60, are more likely to have hypo- between the FDA and a drug company is osteoarthritis—The most common form encouraged throughout the entire drug thyroidism. The condition upsets the of joint disease, characterized by degen- development and review process. The normal balance of chemical reactions in eration of the cartilage that lines joints frequency of communication ensures your body. It seldom causes symptoms and by the formation of reactive bony that questions and issues are resolved in the early stages, but, if left untreat- outgrowths at the boundary of a joint. quickly, often leading to earlier drug ap- ed, it can lead to obesity, joint pain, proval and access by patients. infertility and heart disease.

Medicines in Development for Older Americans 2014 45 Glossary

compound behaves in humans as was tive, identify an optimal dose, and to rheumatoid arthritis—A type of arthritis anticipated from preclinical studies. evaluate further its short-term safety. that particularly attacks the small joints of the hands, wrists and feet. The joints Phase I—Researchers test the drug in a Phase III—The drug is given to a larger, become painful, swollen and stiff, and in small group of people, usually between more diverse patient population, often severe cases, deformed. 20 and 100 healthy adult volunteers, to involving between 1,000 and 5,000 evaluate its initial safety and tolerability patients (but sometimes many more profi le, determine a safe dosage range, thousands), to generate statistically and identify potential side effects. signifi cant evidence to confi rm its safety and effectiveness. Phase III studies are Phase II—The drug is given to volunteer the longest studies and usually take place patients, usually between 100 and 500, in multiple sites around the world. to determine whether the drug is effec-

46 Medicines in Development for Older Americans 2014 The Drug Discovery, Development and Approval Process

Developing a new medicine takes an average of 10-15 years; Tens of thousands of compounds are screened, only 1 is approved.

The Drug Development and Approval Process The U.S. system of new drug approvals is per- pany fi les an IND with the U.S. Food and Drug (but sometime many more thousands), to gener- haps the most rigorous in the world. Administration (FDA) to begin to test the drug ate statistically signifi cant evidence to confi rm It takes 10-15 years, on average, for an experi- in people. The IND shows results of previous its safety and effectiveness. They are the lon- mental drug to travel from lab to U.S. patients, experiments; how, where and by whom the new gest studies, and usually take place in multiple according to the Tufts Center for the Study of studies will be conducted; the chemical structure sites around the world. Drug Development. Tens of thousands of com- of the compound; how it is thought to work in New Drug Application (NDA)/Biologic License pounds may be screened early in development, the body; any toxic effects found in the animal Application (BLA). Following the completion but only one ultimately receives approval. Even studies; and how the compound is manufac- of all three phases of clinical trials, a company medicines that reach clinical trials have only a tured. All clinical trials must be reviewed and ap- analyzes all of the data and fi les an NDA or BLA 16 percent chance of being approved. proved by the Institutional Review Board (IRB) with FDA if the data successfully demonstrate where the trials will be conducted. Progress On average, it costs a company $1.2 billion, both safety and effectiveness. The applications reports on clinical trials must be submitted at including the cost of failures, to get one new contain all of the scientifi c information that the least annually to FDA and the IRB. medicine from the laboratory to U.S. patients, company has gathered. Applications typically according to a 2007 study by the Tufts Center Clinical Trials, Phase I—Researchers test the run 100,000 pages or more. for the Study of Drug Development. More recent drug in a small group of people, usually between Approval. Once FDA approves an NDA or BLA, studies estimate the cost to be even higher. 20 and 100 healthy adult volunteers, to evaluate the new medicine becomes available for physi- its initial safety and tolerability profi le, deter- Once a new compound has been identifi ed in cians to prescribe. A company must continue mine a safe dosage range, and identify potential the laboratory, medicines are usually developed to submit periodic reports to FDA, including side effects. as follows: any cases of adverse reactions and appropriate Clinical Trials, Phase II—The drug is given quality-control records. For some medicines, Preclinical Testing. A pharmaceutical company to volunteer patients, usually between 100 and FDA requires additional trials (Phase IV) to conducts laboratory and animal studies to show 500, to see if it is effective, identify an optimal evaluate long-term effects. biological activity of the compound against the dose, and to further evaluate its short-term targeted disease, and the compound is evalu- Discovering and developing safe and effective safety. ated for safety. new medicines is a long, diffi cult, and expensive Clinical Trials, Phase III—The drug is given to a process. PhRMA member companies invested an Investigational New Drug Application (IND). larger, more diverse patient population, often estimated $51.1 billion in research and develop- After completing preclinical testing, a com- involving between 1,000 and 5,000 patients ment in 2013.

Medicines in Development for Older Americans 2014 47