2013 REPORT 7 2 5 3 6 9 42 46 Staphylococcus Staphylococcus Plasmodium falci- activity against Plasmodium to parum malaria which is resistant treatments. current methicillin-resistant (MRSA). aureus blocking the ability of the smallpox thus other cells, to spread virus to causing disease. it from preventing hepatitis C that inhibits the enzyme hepatitis C that inhibits the enzyme replication. viral essential for Contents Medicines/Vaccines Innovative ...... in the Pipeline ...... Approvals Medicine/Vaccine Key ...... Vaccines Preventative .... Diseases Infectious Drug-Resistant ...... Diseases About Infectious Facts in Medicines/Vaccines ...... Development Glossary ...... Drug Development/ ...... Process Approval • An anti-malarial drug that has shown shown An anti-malarial drug that has • treat antibiotic to A potential new • by that works treatment A novel • fully be never may diseases Infectious knowledge, new However, eradicated. and the continuing technologies, new biopharma- of America’s commitment can help companies research ceutical ever-changing the continuing—and meet diseases. infectious from —threat bacteria, have bacteria, have pseudomonas as common and diffi cult to treat form of form treat cult to and diffi common Throughout history, infectious diseases diseases infectious history, Throughout on the lives toll a devastating taken have the of people around and well-being when pathogens Caused such world. as bacteria or viruses enter a body and the were diseases infectious multiply, in the United cause of death leading vaccines Today, States until the 1920s. have treatments disease and infectious in treatments be effective to proven still diseases but infectious cases, many patients. to pose a very serious threat pathogens, some infectious Recently, such Biopharmaceutical Research Evolves Against Evolves Research Biopharmaceutical 400 Nearly with Medicines Diseases Infectious in Testing and Vaccines treatments. available to resistant become conquered, considered once Diseases reemerged have such as tuberculosis, threat. health as a growing research biopharmaceutical America’s medicines 394 developing are companies threats the many combat to and vaccines of Each diseases. infectious by posed is either in development these medicines the by in clinical trials or under review (FDA). and Drug Administration Food in and vaccines Among the medicines infections, viral for 226 are development herpes and human such as hepatitis, bacte- (HPV);papillomavirus for 124 such as pneumonia and rial infections, fungal infections for 24 tuberculosis; infections. parasitic and 15 for for of medicines potential Some examples include: diseases ghting infectious fi the most for treatment A combination •

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12 Medicines in Development in Development Medicines Diseases Infectious For Bacterial

PRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES BIOPHARMACEUTICALRESEARCH AMERICA’S BY PRESENTED Infectious Diseases Infectious and Parasites A Report Fungi Viruses, Caused by Bacteria, on Diseases MEDICINES IN DEVELOPMENT MEDICINES Key Issues

Innovative Medicines and Vaccines in the Pipeline ANTIBIOTIC RESISTANT

Bacterial Diarrhea—About 3 million cases of Clostridium I N F E C T I O N S diffi cile-associated diarrhea (CDAD) occur each year in the United States. CDAD is caused by an overgrowth of the gram-positive bacteria naturally found in the lower gastroin- testinal tract. An antibacterial lipopeptide in development AFFECT for the treatment CDAD has a more rapid antibacterial action than available treatments.

Hepatitis C—Hepatitis C virus (HCV) affects 180 million 2 MILLION people worldwide, including more than 4 million Americans, + according to the National Institute of Allergy and Infectious AMERICANS Diseases. The Centers for Disease Control and Prevention ANNUALLY (CDC) projects that the death toll in the United States from hepatitis C will triple in the next 20 years, eclipsing that of AIDS. A potential medicine is in development in a combina- Source: Centers for Disease Control and Prevention (CDC) tion treatment for HCV genotype 1—the most common and diffi cult to treat form of HCV—is an inhibitor of the hepatitis C virus NS5B—a virally encoded enzyme that is essential for the conserved parts of the p24 protein. A sustained immune viral replication. response against the p24 protein has shown to be associated with delayed disease progression. HIV Infection—A therapeutic vaccine in development is tar- geting the low-mutating (conserved) parts from the protein Impetigo—Impetigo is a highly contagious skin infection p24 of the HIV virus. The vaccine consists of four peptides caused by the Staphylococcus aureus bacteria entering a that are modifi ed to increase the immune response against small break in the skin, such as a cut, scratch or insect bite. It affects approximately 1 million people annually in the United States, primarily infants and children, and causes itchy and painful sores. A novel synthetic antimicrobial medicine in INFECTIOUS DISEASES development is specifi cally designed and developed to mimic the body’s natural defense against infection. In clinical trials, RESEARCH & DEVELOPMENT the clinical response rate in patients at the end of treatment ranged from 85 percent to 92 percent compared to historical placebo rates of 30 percent to 50 percent.

Malaria—Globally, about 275 million cases of malaria are diagnosed each year, killing more than 1 million people—about 3,000 people every day, according to the World Health Orga- 394 nization. A novel anti-malarial drug in development has shown MEDICINES activity against Plasmodium falciparum malaria that is resistant AND VACCINES or sensitive to chloroquine, a common malaria treatment. IN DEVELOPMENT AGAINST INFECTIOUS DISEASES Multi-Drug Resistant (MDR) Infection—Multi-drug resistance occurs when a bacteria develops the ability to survive expo- sure to more than one available therapy. The incidence of drug-resistant strains of Staphylococcus aureus has recently Source: PhRMA 2013 Medicines in Development for Infectious Diseases

2 Medicines in Development Infectious Diseases 2013 Key Issues

been on the rise. According to the CDC, more than 90,000 Americans become infected each year with life-threatening RESEARCH FOCUS: HEPATITIS C drug-resistant staph—methicillin-resistant Staphylococcus Hepatitis C is a viral disease that attacks the liver, aureus, or MRSA. A novel medicine in development inhibits leading to many complications, including cirrhosis, the beta lactamase enzyme produced by various types of liver transplants, liver cancer and death. It affects bacteria which can provide resistance to some antibiotics. about 3.2 million people in the United States. The The medicine is being studied in combination with a broad rate of detectable hepatitis C virus in the blood 24 spectrum cephalosporin for the treatment of MRSA—for weeks after treatment improved from 10 percent in both gram-negative and gram-positive bacteria. the 1990s to 80 percent today among hepatitis C Another medicine in development to combat MRSA is in a patients. This increase refl ects growing knowledge new class of antibiotics called aminomethylcyclines. In test- of the disease and treatments that moved towards ing, it has demonstrated broad-spectrum antibacterial activity today’s triple therapy regimens, which include and particularly potent activity against gram-positive bacteria recently approved “direct acting antivirals.” that are resistant to existing antibacterials.

Smallpox (Orthopoxvirus Infections)—Smallpox, caused by the variola virus, is no longer found in the environment, Key Medicine and Vaccine Approvals but is considered a formidable biowarfare threat. A novel treatment in development works by blocking the ability of Fungal Infections the virus to spread to other cells, thus preventing it from Noxafi l® (posaconazole) was approved for the prevention of causing disease. It is being studied to prevent the disease invasive fungal infections caused by Aspergillus and Candida in non-vaccinated individuals, to treat the disease in non- in patients 13 years of age and older who are at high risk of symptomatic people exposed to smallpox, to treat those developing these infections due to being severely immuno- with smallpox symptoms, and as an adjuvant to vaccination compromised. It is the fi rst and only antifungal approved by by combining with smallpox vaccines to prevent disease the FDA for the prevention of invasive fungal infections caused and reduce vaccine-related complications. by Aspergillus. Invasive fungal infections most often occur in people who are immunocompromised or immunosuppressed and are increasingly caused by molds such as Aspergillus. ANTIBIOTIC RESISTANT Mycamine™ (micafungin sodium for injection), an antifungal, was approved for the prevention of Candida infections in I N F E C T I O N S patients undergoing hematopoietic stem cell transplantation and the treatment of esophageal candidiasis. The medicine is a member of a new class of antifungal agents called echino- candins, which specifi cally targets the wall of fungal cells to CAUSE treat the infection.

Hepatitis ~23,000 Victrelis™ (boceprevir) is a fi rst-in-class medicine approved for the treatment of chronic hepatitis C in combination with inter- DEATHS feron therapy for those with compensated liver disease. Victrelis is a hepatitis C protease inhibitor, which works by inhibiting a ANNUALLY key viral enzyme and preventing the virus from multiplying.

Baraclude™ (entecavir) was approved for the treatment

Source: Centers for Disease Control and Prevention (CDC) of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in

Medicines in Development Infectious Diseases 2013 3 Key Issues

serum aminotransferases or histologically active disease. The drug is an oral antiviral that is designed to block the replica- tion of hepatitis B virus in the body by interfering with the ANTIBIOTIC RESISTANT virus’s ability to infect cells. I N F E C T I O N S

HIV Infection 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 Intelence™ (etravirine) is the fi rst non-nucleoside reverse 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 transcriptase inhibitor (NNRTI) to show antiviral activity in 1 1 1 1 ACCOUNT1 1 1 1 1 1FOR1 1 1 1 1 1 patients with NNRTI-resistant virus. It was approved for the 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 treatment of HIV infection, in combination with other antiret- 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 roviral agents, in treatment-experienced adult patients who 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 have evidence of viral replication and resistance to NNRTI 1 1 1 $1 201 1 1 BILLION1 1 1 1 1 1 1 1 1 $ $ $ $ $ $ $ $ and other antiretroviral agents. 1 1 1 1 IN1 DIRECT1 1 HEALTH1 1 CARE1 1 COSTS1 1 1 1 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 Isentress™ (raltegravir) was approved for use in combina- 1 1 1 1 1 ANNUALLY1 1 1 1 1 1 1 1 1 1 1 tion with other antiretroviral agents for the treatment of 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 1 $ 1 HIV-1 infection in treatment-experienced adult patients who 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 have evidence of viral replication and resistance to multiple Source: Centers for Disease Control and Prevention (CDC) antiretroviral agents. Isentress is the fi rst in a new class of antiretroviral drugs known as integrase inhibitors. It is designed to interfere with the enzyme that delivers HIV viral than 10 years. Selzentry blocks the CCR5 co-receptor, the DNA into human DNA, thereby limiting the ability of HIV virus’ predominant entry into white blood cells (T-cells) by to replicate and infect new cells. stopping the virus on the outside surface of the cells before it enters. It has been shown to signifi cantly reduce viral load Selzentry™ (maraviroc) is the fi rst new medicine in the class and increase T-cell counts in treatment-experienced patients of HIV medicines—known as CCR5 antagonists—in more infected with a specifi c type of HIV.

PROGRESS AGAINST HIV/AIDS: THE EVOLUTION OF VALUE FOR PATIENTS Over the past 20 years, research advances in HIV/AIDS have transformed the treatment standard for many patients. HIV/AIDS was once an acute, fatal illness and is now a manageable, chronic disease for those who have access to medications. In the United States alone, death rates have fallen more than 80 percent since 1995 as a result of the development and use of multiple drugs used in innovative combinations, known as highly active antiretroviral therapy (HAART).

Progress against HIV/AIDS didn’t happened through one single breakthrough, but through a series of stages, marked by both the introduction of new treatment options and constant learning about their optimal use and clinical value. FDA approval, which is based on rigorous clinical trials in controlled settings, marks the starting point for the continuing evolution in our understanding of a treatment’s full value for patients. As is the case for HIV/AIDS, the full value of new treatments is often not fully known at the time of FDA approval, but is realized over time as new treatments build on one another and real world knowledge is accumulated.

The ongoing introduction of new HIV/AIDS therapies, and continuous research into their optimal use in patient care, has revealed additional value for treatments beyond what was known at the time they were introduced. These include: • Use in combination with other therapeutics • Use earlier in treatment line or disease state • Use in treatment of different diseases, such as cancer

4 Medicines in Development Infectious Diseases 2013 Key Issues

Infl uenza FluBlok® (infl uenza vaccine) is the fi rst recombinant, highly INFECTIOUS DISEASES purifi ed, egg-free infl uenza vaccine approved. The vaccine is manufactured without using live infl uenza virus and is 100 R E S I S T A N C E percent egg-free. The novel manufacturing method allows the vaccine to be made quickly and it does not rely on egg NEARLY supply or available infl uenza virus. It is also preservative, antibiotic and adjuvant free. FluBlok was developed in partnership with the Biomedical Advanced Research and Development Authority (BARDA), a division of the U.S. Department of Health and Human Services. 50% OF ANTIBIOTICS Flucelvax® (infl uenza virus vaccine) is the fi rst cell-culture de- or rived vaccine approved to protect against seasonal infl uenza in UNNECESSARILY adults. It is manufactured using full-scale cell-culture technology, INAPPROPRIATELY an alternative to traditional egg-based production. Cell-culture PRESCRIBED technology uses a mammalian cell line rather than chicken eggs to grow virus strains. It does not contain any preservatives or Source: Centers for Disease Control and Prevention (CDC) antibiotics. In clinical trials, Flucelvax showed to be 83.8 percent effective in preventing the fl u when compared to placebo. Preventative Vaccines: Positive Tuberculosis Impact to Health and Society Sirturo™ (bedaquiline) received accelerated approval as a com- bination therapy for adults with multi-drug resistant pulmonary Vaccines are one of the most profound achievements of bio- tuberculosis (MDR-TB). It is the fi rst new TB therapy in 40 years medical science and public health. Spanning more than 200 with a new mechanism of action. Sirturo inhibits mycobacterial years of research and development, 10 infectious diseases ATP (adenosine 5’-triphosphate) synthase, an enzyme that is need- have been at least 90 percent eradicated in the United States ed for the generation of energy in Mycobacterium tuberculosis. thanks to vaccines. This has protected millions of children and families from preventable illness.

The prevention of disease has an enormous impact on the ANTIBIOTIC RESISTANT health of individuals and communities overall, as well as a I N F E C T I O N S substantial impact on the economy by reducing health care costs and avoiding lost productivity. Preventative vaccines are given to individuals, but see their greatest benefi t when entire populations are immunized. When a high concentration ACCOUNT FOR of vaccination is attained in a community with an effective vaccine, disease transmission can be successfully disrupted. When disease transmission is disrupted, even those who were not vaccinated, or those who did not receive immu- $35 BILLION nity from the vaccine, benefi t from vaccination and can be protected from the disease. This is known as herd immu- IN LOST PRODUCTIVITY nity—where immunization coverage is suffi cient enough to prevent the transmission of a disease to the susceptible ANNUALLY population. This is especially important for the young, the elderly and those with compromised immune systems.

Source: Centers for Disease Control and Prevention (CDC)

Medicines in Development Infectious Diseases 2013 5 Key Issues

Drug-Resistant Infectious Diseases EMERGING AND RE-EMERGING More than 2 million people in the United States get infec- INFECTIOUS DISEASES tions that are resistant to antibiotics and about 23,000 Infectious diseases have been emerging and re- die as a result of the resistant infections, according to a emerging causing great suffering for centuries. new report from the CDC. While diffi cult to calculate, Greek, Roman and Persian civilizations documented the CDC report also cites the economic cost of antibiotic new epidemics and the bubonic plague or “Black resistance to the U.S. economy as high as $20 billion in Death” in the 14th century killed a third of the direct healthcare costs and another $35 billion in lost population in Europe. In recent times, the most productivity (2008 dollars). startling example of an emerging infectious disease has been HIV/AIDS. Emerging infectious diseases include previously unknown infectious “ Antibiotic resistance is rising for many agents, known agents that have spread to new di erent pathogens that are threats to populations and locations, known agents whose health. If we don’t act now, our medicine role in disease is only now understood, and the re-emergence of infectious diseases that had chest will be empty and we won’t have previously declined signifi cantly, but are now on the antibiotics we need to save lives.” the rise. Current emerging and re-emerging threats

—Tom Frieden, MD, MPH, Director, CDC according to NIAID include: anthrax, antimicrobial resistance, botulism, campylobacteriosis, dengue fever, ehrlichiosis, E. coli, group A streptococcal The new report—Antibiotic Resistance Threats in the infections, hepatitis, infl uenza, Lyme disease, United States, 2013—assessed the current impact of these plague, Prion diseases, SARS, salmonellosis/ antibiotic-resistant infections and the 10-year projection of shigella, smallpox, tuberculosis, tularemia, and their impact. The diseases were ranked as either urgent West Nile virus. threats, serious threats or concerning threats using seven

factors to determine an infection’s rank, including health impact, economic impact and how common the infection INFECTIOUS DISEASES is, among others.

E M E R G I N G T H R E A T S Urgent Threats—Clostridium diffi cile, carbapenem-resistant enterobacteriaceae (CRE), drug-resistant Neisseria gonorrhoeae.

SINCE 1970s Serious Threats—Multidrug-resistant Acinetobacter, drug- resistant Campylobacter, fl uconazole-resistant Candida, extended spectrum β-lactamase producing enterobacteria- INFECTIOUS ceae (ESBLs), vancomycin-resistant Enterococcus (VRE), DISEASES multidrug-resistant Pseudomonas aeruginosa, drug-resistant DISCOVERED non-typhoidal Salmonella, drug-resistant Salmonella Typhi, 40 drug-resistant Shigella, methicillin-resistant Staphylococcus —INCLUDING— aureus (MRSA), drug-resistant Streptococcus pneumoniae, SWINE and AVIAN FLU drug-resistant tuberculosis. MERS and SARS Concerning Threats—Vancomycin-resistant Staphylococcus aureus (VRSA), erythromycin-resistant Group A Streptococ- Source: World Health Organization (WHO) cus, clindamycin-resistant Group B Streptococcus.

6 Medicines in Development Infectious Diseases 2013 Facts

Facts About Infectious Diseases INFECTIOUS DISEASES Bacterial Infections VACCINATION FOR PREVENTION • In the United States, incidence of naturally-acquired

anthrax is extremely rare—about 1-2 cases of cutaneous hepatitis A NOW PREVENTABLE disease per year.1 hepatitis B NOW PREVENTABLE • More than 1.2 million cases of bacterial meningitis are estimated to occur each year worldwide. Without treat- cancer caused by viruses NOW PREVENTABLE ment, the fatality rate can be as high as 70 percent.1 pneumonia NOW PREVENTABLE

• Bacterial vaginosis is the most common cause of vaginal TARGETED FOR ELIMINATION rubella infection among women, with an estimated 21.2 million women aged 14 – 49 affected in the United States.1 TARGETED FOR ELIMINATION measles

• About 3 million cases of C. diffi cile infection diarrhea TARGETED FOR ELIMINATION polio 2 and colitis occur each year in the United States. About ERADICATED smallpox 14,000 deaths are attributed to the infection each year.1 Source: PhRMA 2013 Vaccine Fact Book • Gram-negative bacteria are responsible for more than 30 percent of hospital-acquired infections and predominate in hospital-acquired pneumonia.3 • More than 11,000 tuberculosis cases were reported in 1 • Impetigo —the most common bacterial skin infection and the United States in 2010. the third most common skin disease among children— • Urinary tract infections (UTIs) account for nearly 7 million accounts for approximately 10 percent of skin problems offi ce visits and 1 million emergency department visits, observed in pediatric clinics.4 resulting in 100,000 hospitalizations.2 • Otitis externa affects 4 in 1,000 people annually in the • The estimated annual cost of community-acquired UTIs is United States.5 approximately $1.6 billion.2 • In 2011, sepsis/septicemia was the 11th leading cause of • Nearly 2 million people in the United States acquire an death overall in the United States. Between 20 percent infection while in a hospital (nosocomial) each year, and 50 percent of patients with sepsis die.1 resulting in 90,000 deaths. More than 70 percent of the bacteria that cause these infections are resistant to at least one of the antibiotics commonly used to treat them.1 ADDRESSING UNMET NEED FOR NEW ANTIBACTERIAL TREATMENTS • Antibiotic resistance in the United States costs more than an estimated $20 billion a year in health care costs, Bringing new antibacterial treatments to market is $35 million in other societal costs, and more than 8 mil- a challenging process. A Lancet article published lion additional days that people spend in the hospital.1 this year fi nds several obstacles for developing antibacterials and proposes the implementation Fungal Infections of development scenarios within the existing regulatory system that would allow for either • Candida fungal infections account for approximately disease-based or pathogen-based label indications 15 percent of all hospital-acquired infections, more than that would promote the most appropriate use 72 percent of all hospital-acquired fungal infections, and of the new therapeutic and would facilitate a up to 15 percent of all hospital-acquired bloodstream sustainable research and development structure. infections.4

Medicines in Development Infectious Diseases 2013 7 Facts

• Volvovaginal candidiasis accounts for about one-third estimated 20 million people are currently infected, and an of vaginitis cases. Nearly 50 percent of premenopausal estimated 6.2 million new HPV infections occur annually.1 women report having had at least one episode.6 • Cervical cancer can be caused by certain types of HPV. • Onychomycosis is estimated to be responsible for up to In 2013, about 12,340 new cases of cervical cancer are 50 percent of all nail diseases.4 estimated to occur in the United States, and some 4,030 women will die.1 Parasitic Infections • About $4 billion are spent annually on the management • Between 6 million and 12 million head lice (pediculosis) of conditions from HPV infections, exceeding the eco- infestations occur each year in the United States among nomic burden of any other sexually transmitted infection children 3 to 11 years of age.1 except HIV.1 • currently threatens 350 million men, women Leishmaniasis • The CDC estimates that pandemic H1N1 infl uenza virus in and children in 88 countries around the world. If left un- 2009 caused more than 60 million Americans to become treated, the fatality rate for in develop- visceral leishmaniasis ill and led to more than 270,000 hospitalizations and ing countries can be as high as 100 percent within 2 years.7 12,500 deaths.1 • More than 3 billion people (half the world’s population) • Although the incidence of infl uenza can vary widely live in areas at risk of malaria transmission in 106 coun- between years, approximately 36,000 deaths and more tries and territories. Worldwide, in 2010, there were 216 than 200,000 hospitalizations are directly associated million cases of malaria and 655,000 deaths. About 86 with infl uenza every year in the United States.8 percent of deaths globally were in children, and an esti- mated 91 percent of deaths in 2010 were in the African • Approximately 5.6 million cases of pneumonia occur an- Region.1 nually in the United States. In 2001, infl uenza and pneu- monia together were the eighth leading cause of death in Viral Infections the United States.4

• At least 60 percent of the U.S. population has been • Each year, up to 5 million children younger than age 4 exposed to , with a prevalence of cytomegalovirus (CMV) acquire a respiratory syncytial virus (RSV) infection, and more than 90 percent in high-risk groups (e.g., unborn more than 125,000 are hospitalized in the United States babies whose mothers become infected with CMV during because of it.4 pregnancy or people with HIV).4

• An estimated 700,000 to 1.4 million people in the United Sources: States are chronically infected with hepatitis B.1 1. U.S. Center for Disease Control and Infection, www.cdc.gov • Hepatitis C virus infection is the most common chronic blood-borne infection in the United States; approximately 2. National Center for Biotechnology Information, National 3.2 million persons are chronically infected.1 Institutes of Health, www.ncbi.nlm.nih.gov 3. The New England Journal of Medicine, Massachusetts • At least 50 million people have genital herpes (caused by Medical Society, www.nejm.org the herpes simplex virus) in the United States.6 4. Medscape, www.emedicine.medscape.com • The CDC estimates that 1,148,200 people ages 13 years 5. Epocrates, online.epocrates.com and older are living with HIV infection, including 207,600 who are unaware of their infection. In 2011, an estimated 6. Wolters Kluwer Health, UpToDate, Inc., 49,273 people were diagnosed with HIV infection in the www.uptodate.com United States.1 7. World Health Organization, www.who.int

• Human papillomavirus (HPV) infection is the most com- 8. Medical News, www.news-medical.net mon sexually transmitted infection in the United States. An

8 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase*

AB103 AtoxBio necrotizing soft tissue infections Phase II (CD28-antigen inhibitor) Ness Ziona, Israel (Fast Track) www.atoxbio.com ORPHAN DRUG Fast-Track Drugs & Biologics North Potomac, MD

ACAM-Cdi Sano Pasteur Clostridium di cile infection Phase III (Clostridium di cile toxoid vaccine) Swiftwater, PA (prevention) (Fast Track) www.sano .com

ACE527 TD Vaccines prevention of traveler’s diarrhea Phase II (ETEC vaccine) Odense, Denmark caused by Escherichia coli www.tdvaccines.com PATH www.path.org Seattle, WA

acellular pertussis combos Novartis Vaccines diphtheria, pertussis, tetanus Phase I Cambridge, MA www.novartisvaccines.com

ACHN-975 Achaogen pseudomonal infections Phase I (LpxC inhibitor) South San Francisco, CA www.achaogen.com

actoxumab/bezlotoxumab Merck Clostridium di cile infection Phase III (MK-3415A/MK-6072) Whitehouse Station, NJ www.merck.com

Aeroquin™ Aptalis Pharma treatment of pulmonary infection due Phase III levo oxacin inhalation solution Bridgewater, NJ to Pseudomonas aeruginosa and other www.aptalis.com ORPHAN DRUG bacteria in patients with cystic  brosis

AFN-1252 A nium Pharmaceuticals acute bacterial skin and skin structure Phase II (enoyl-ACP reductase inhibitor) Austin, TX infections www.afnm.com

AFN-1720 A nium Pharmaceuticals staphylococcal infection (treatment) Phase I (enoyl-ACP reductase inhibitor) Austin, TX www.afnm.com

AL-60371 Alcon otitis externa Phase III (otic suspension) Fort Worth, TX www.alcon.com

amikacin/fosfomycin inhalation Cardeas Pharma ventilator-associated pneumonia, Phase I system Seattle, WA ventilator-associated www.cardeaspharma.com tracheobronchitis

anthrax immune globulin Cangene anthrax Phase III (human) Winnipeg, Canada www.cangene.com ORPHAN DRUG

*For more information about a specifi c medicine or company in the report, please use the website provided.

Medicines in Development Infectious Diseases 2013 9 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

anthrax vaccine (oral) National Institute of Allergy and anthrax Phase I Infectious Diseases (NIAID) www.paxvax.com Bethesda, MD PaxVax San Diego, CA

Anthrivig™ Emergent BioSolutions anthrax Phase III human anthrax immunoglobulin Rockville, MD www.emergentbiosolutions.com ORPHAN DRUG

antimicrobial vaccine Immunitor USA bacterial infections Phase I/II College Park, MD www.immunitor.com

AR-301 Aridis Pharmaceuticals S. aureus pneumonia Phase I/II (anti-Sa-mAb) San Jose, CA www.aridispharma.com

Arikace® Insmed cystic  brosis-associated respiratory Phase III inhaled liposomal amikacin Monmouth Junction, NJ tract infection caused by www.insmed.com ORPHAN DRUG Pseudomonas aeruginosa ------non-tuberculosis mycobacterial Phase II infections (Fast Track) www.insmed.com

ATM AVI AstraZeneca serious bacterial infections Phase I (avibactam/aztreonam  xed-dose Wilmington, DE www.astrazeneca.com combination)

auriclosene NovaBay Pharmaceuticals impetigo Phase II/III (NVA-422) Emeryville, CA (topical gel) www.novabay.com Galderma www.galderma.com Fort Worth, TX ------NovaBay Pharmaceuticals infectious conjunctivitis Phase II Emeryville, CA (eye drops) www.novabay.com ------urinary tract infections Phase II (irrigation solution) www.novabay.com

avaro oxacin Furiex Pharmaceuticals community-acquired bacterial Phase II (JNJ-Q2) Morrisville, NC pneumonia, skin and soft tissue www.furiex.com infections (Fast Track)

AZD0914 AstraZeneca gonorrhea Phase I Wilmington, DE www.astrazeneca.com

AZD5847 AstraZeneca tuberculosis Phase II (posizolid) Wilmington, DE www.astrazeneca.com

10 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

BC-3781 Nabriva Therapeutics acute bacterial skin and skin structure Phase II (pleuromutilin) Vienna, Austria infections www.nabriva.com

Bexsero® Novartis Vaccines meningitis B (prevention) Phase II meningococcal group B Cambridge, MA www.novartisvaccines.com quadrivalent recombinant vaccine

biapenem (RPX2003)/ Rempex Pharmaceuticals gram-negative bacterial infections Phase I beta-lactamase inhibitor San Diego, CA www.rempexpharma.com (RPX7009)

BioThrax® Emergent BioSolutions anthrax (post-exposure prevention) Phase III anthrax vaccine adsorbed Rockville, MD (Fast Track) www.emergentbiosolutions.com (subcutaneous)

brilacidin Cellceutix acute bacterial skin and soft tissue Phase II Beverly, MA infections www.cellceutix.com

C-1205 ConjuGon urinary tract infections (prevention) Phase I Madison, WI www.conjugon.com

cadazolid Actelion Pharmaceuticals US Clostridium di cile-associated Phase III South San Francisco, CA diarrhea www.actelion.com

Carbavance™ Rempex Pharmaceuticals gram-negative bacterial infections Phase I (RPX2014)/(RPX7009) San Diego, CA www.rempexpharma.com beta-lactamase inhibitor

Cayston® Gilead Sciences bronchiectasis, burkholderia Phase III aztreonam inhalation Foster City, CA infections associated with cystic www.gilead.com ORPHAN DRUG  brosis, cystic  brosis-associated respiratory tract infections (children)

CAZ AVI AstraZeneca complicated intra-abdominal Phase III (avibactam/ceftazidime  xed-dose Wilmington, DE infections (cIAI), complicated urinary www.astrazeneca.com combination) Forest Laboratories tract infections (cUTI), www.frx.com New York, NY hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP)

CBM588 Osel Clostridium di cile-associated disease Phase II/III (MIYA-BM) Mountain View, CA www.oselinc.com

ceftolozane/tazobactam Cubist Pharmaceuticals cIAI, cUTI (Fast Track) Phase III (CXA-201) Lexington, MA www.cubist.com ------hospital-acquired/ventilator-associated Phase II bacterial pneumonia (HABP/VABP) www.cubist.com (Fast Track)

Medicines in Development Infectious Diseases 2013 11 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

CG400549 CG Pharmaceuticals methicillin-resistant Staphylococcus Phase II (enoyl-ACP reductase inhibitor) Emeryville, CA aureus infection (MRSA) www.cgpharma.com

cipro oxacin dry powder inhalation Bayer HealthCare Pharmaceuticals chronic lung infection caused by Phase II (DPI) Whippany, NJ Pseudomonas aeruginosa www.bayerpharma.com Novartis Pharmaceuticals www.novartis.com East Hanover, NJ

cipro oxacin/ uocinolone Salvat otitis externa Phase III otic solution Barcelona, Spain www.salvatbiotech.com

CollaRx® Innocoll surgical site infections Phase III gentamicin implant County Westmeath, Ireland (Fast Track) www.innocollinc.com

CSE-1034 Venus Remedies nosocomial infections application submitted (ceftriaxone/disodium-edetate/ Panchkula, India www.venusremedies.com sulbactam)

CXL AstraZeneca MRSA Phase II (avibactam/ceftaroline  xed-dose Wilmington, DE www.astrazeneca.com combination) Cerexa www.cerexa.com Oakland, CA

dalbavancin Durata Therapeutics acute bacterial skin and skin structure application submitted (lipoglycopeptide antibiotic) Chicago, IL infections caused by susceptible www.duratatherapeutics.com gram-positive microorganisms, including MRSA

DCN01 Deacon Biosciences ophthalmic infections (prevention) Phase II New York, NY

dela oxacin Melinta Therapeutics acute bacterial skin and skin structure Phase III New Haven, CT infections, including MRSA www.melinta.com

delamanid Otsuka Pharmaceutical tuberculosis Phase III (OPC-67683) Princeton, NJ www.otsuka.com ORPHAN DRUG

DFA-02 Dr. Reddy’s Laboratories postoperative bacterial infections Phase I/II (gentamicin/vancomycin) Hyderabad, India (prevention) www.drreddys.com

Di cid® Cubist Pharmaceuticals pediatric Clostridium di cile infection Phase II  daxomicin Lexington, MA (prevention) www.cubist.com ORPHAN DRUG

12 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

DTP-HepB-Polio-Hib hexavalent Merck diphtheria, tetanus, pertussis, Phase III vaccine Whitehouse Station, NJ hepatitis B, poliomyelitis, www.merck.com (PRI51/V419) Sano Pasteur Haemophilus in uenzae type b www.sano .com Swiftwater, PA (pediatric) (see also viral)

E-101 Exoxemis postoperative bacterial infections Phase III (antimicrobial topical liquid) Little Rock, AR (prevention) www.exoxemis.com (see also viral)

E5564 Eisai severe sepsis Phase III Woodcli Lake, NJ (Fast Track) www.eisai.com

eravacycline Tetraphase Pharmaceuticals complicated intra-abdominal Phase III (TP-434) Watertown, MA infections www.tphase.com

ETI-204 Elusys Therapeutics anthrax Phase I (anthrax toxin inhibitor mAb) Pine Brook, NJ (Fast Track) www.elusys.com ORPHAN DRUG

 na oxacin MerLion Pharmaceuticals otitis externa Phase III Singapore www.merlionpharma.com

GSK134612 GlaxoSmithKline meningococcal infection groups Phase III (MenACWY-TT conjugated vaccine) Research Triangle Park, NC A,C,W,Y (prevention) www.gsk.com

GSK692342 Aeras tuberculosis Phase II (tuberculosis recombinant vaccine) Rockville, MD www.aeras.org GlaxoSmithKline www.gsk.com Research Triangle Park, NC

GSK1322322 GlaxoSmithKline bacterial infections Phase II (polypeptide deformylase Research Triangle Park, NC www.gsk.com inhibitor)

GSK2140944 GlaxoSmithKline bacterial infections Phase I (type 2 topoisomerase inhibitor) Research Triangle Park, NC www.gsk.com

IC43 Novartis Vaccines nosocomial infection caused by Phase II (Pseudomonas aeruginosa vaccine) Cambridge, MA Pseudomonas aeruginosa (prevention) www.novartisvaccines.com Valneva Vienna, Austria

IC84 Novartis Vaccines Clostridium di cile infection Phase I (recombinant fusion protein Cambridge, MA (prevention) www.novartisvaccines.com vaccine) Valneva Vienna, Austria

Medicines in Development Infectious Diseases 2013 13 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

ID-93/GLA-SE Aeras tuberculosis (prevention) Phase I (recombinant fusion protein Rockville, MD www.aeras.org vaccine) Infectious Disease Research Institute www.idri.org Seattle, WA

LACTIN-V Osel bacterial vaginosis, recurrent urinary Phase II Mountain View, CA tract infections www.oselinc.com

LFF571 Novartis Pharmaceuticals Clostridium di cile infection Phase II (peptide elongation factor Tu East Hanover, NJ www.novartis.com inhibitor)

Lyme disease vaccine Baxter HealthCare Lyme disease (prevention) Phase I/II Deer eld, IL www.baxter.com

ME1100 Meiji Seika Pharma hospital-acquired bacterial Phase I (arbekacin inhalation) Tokyo, Japan pneumonia, ventilator-associated www.meiji-seika-pharma.co.jp bacterial pneumonia

MEDI4893 MedImmune hospital-acquired pneumonia, serious Phase I (anti-alpha toxin YTE mAb) Gaithersburg, MD Staphylococcus aureus infection www.medimmune.com

MenABCWY Novartis Vaccines meningitis B (prevention) Phase II multivalent conjugate vaccine Cambridge, MA www.novartisvaccines.com

Meninge ACWY Sano Pasteur meningococcal infection (prevention) Phase II (second-generation meningococcal Swiftwater, PA www.sano .com conjugate infant vaccine)

MK-7655 Merck intra-abdominal infections, urinary Phase II (beta lactamase inhibitor) Whitehouse Station, NJ tract infections www.merck.com

MnB rLP2086 P zer meningitis B (adolescents and young Phase III (PF-05212366) New York, NY adults) (prevention) www.p zer.com

MRX-1 MicuRx Pharmaceuticals MRSA, vancomycin-resistant Phase I (protein synthesis inhibitor) Hayward, CA enterococcal infections (VRSA) www.micurx.com

nemonoxacin TaiGen Biotechnology community-acquired pneumonia Phase III (oral) Taipei, Taiwan www.taigenbiotech.com.tw ------diabetic foot infections Phase II www.taigenbiotech.com.tw

14 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

nitric oxide topical NB Therapeutics skin and soft tissue infections, Phase II Bristol, PA tinea pedis www.nitricbio.com

NmVac4 JN-International Medical meningococcal infection groups Phase I (meningococcal groups ACWY Omaha, NE A,C,W,Y (prevention) www.jn-vaccines.org conjugate vaccine)

NuThrax™ Emergent BioSolutions anthrax (post-exposure prevention) Phase II anthrax vaccine adsorbed with Rockville, MD (Fast Track) www.emergentbiosolutions.com CPG7909 adjuvant

omadacycline Paratek Pharmaceuticals acute bacterial skin and soft tissue Phase II Boston, MA infections, community-acquired www.paratekpharm.com bacterial infections, urinary tract infections

oritavancin The Medicines Company gram-positive infections, skin and soft Phase III Parsippany, NJ tissue infections www.themedicinescompany.com ------bacteremia Phase II www.themedicinescompany.com

OTO-201 Otonomy otitis media (pediatric) Phase I (cipro oxacin intratympanic) San Diego, CA www.otonomy.com

ozenoxacin Ferrer Internacional impetigo Phase III Barcelona, Spain www.ferrergrupo.com

P128 Gangagen staphylococcal infection Phase I/II (recombinant protein) Newark, CA www.gangagen.com

PF-06290510 P zer staphylococcal infection Phase II (4-antigen Staphylococcus aureus New York, NY www.p zer.com vaccine, SA4g)

PF-06425090 P zer Clostridium di cile colitis Phase I (Clostridium di cile vaccine) New York, NY www.p zer.com

plague vaccine injectable DynPort Vaccine Yersinia infection Phase II completed Frederick, MD www.csc.com/dvc

plazomicin Achaogen multi-drug resistant bacterial Phase II (ACHN-490) South San Francisco, CA infections www.achaogen.com

Medicines in Development Infectious Diseases 2013 15 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

PreviThrax® Emergent BioSolutions anthrax (Fast Track) Phase II recombinant protective antigen Rockville, MD www.emergentbiosolutions.com (rPA) anthrax vaccine, puri ed

Prevnar 13® P zer pneumococcal infection (prevention) application submitted pneumococcal vaccine conjugate New York, NY in HIV-infected adults, preterm www.p zer.com 13-valent neonates and children and adolescents with sickle cell disease

Pseudomonas aeruginosa KaloBios Pharmaceuticals cystic  brosis-associated respiratory Phase II anti-PcrV pegylated antibody South San Francisco, CA tract Pseudomonas aeruginosa www.kalobios.com fragment infection (KB001A) ------KaloBios Pharmaceuticals ventilator-associated pneumonia Phase I South San Francisco, CA (prevention) (Fast Track) www.kalobios.com Sano Pasteur www.sano .com Swiftwater, PA

PXVX-0200 PaxVax cholera Phase III (oral, live attenuated vaccine) San Diego, CA www.paxvax.com

Quadracel® Sano Pasteur diphtheria, tetanus, pertussis and Phase III diphtheria and tetanus toxoids Swiftwater, PA polio vaccine (in children 4 – 6 years www.sano .com and acellular pertussis vaccine of age) adsorbed combined with (see also viral) inactivated poliomyelitis vaccine

radezolid Melinta Therapeutics community-acquired pneumonia, Phase II (enhanced oxazolidinone) Lincolnshire, IL uncomplicated skin and skin structure www.melinta.com infections

ramoplanin oral Nanotherapeutics Clostridium di cile infection Phase II Alachua, FL (Fast Track) www.nanotherapeutics.com

RBX2660 Rebiotix recurrent Clostridium di cile Phase II (microbiota suspension) Roseville, MN infection (Fast Track) www.rebiotix.com

RHB-105 RedHill BioPharma H. pylori infection Phase III (amoxicillin/omeprazole/rifabutin Tel Aviv, Israel ( rst-line therapy) www.redhillbio.com  xed-dose combination)

rifalazil ActivBiotics Pharma chlamydial infection Phase II Atlanta, GA

Rifamycin SV MMX® Santarus traveler’s diarrhea Phase III San Diego, CA www.santarus.com

RUT58-60 Ruthigen post-abdominal surgery bacterial in clinical trials Santa Rosa, CA infections (prevention) www.ruthigen.com

16 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

S-649266/GSK2696266 GlaxoSmithKline bacterial infections Phase I (cephalosporin) Research Triangle Park, NC www.gsk.com Shionogi www.shionogi.com Florham Park, NJ

SAR279356 Sano serious infections Phase II (anti-PANG mAb) Bridgewater, NJ www.sano .com

solithromycin Cempra Pharmaceuticals community-acquired pneumonia Phase III (CEM-101) Chapel Hill, NC www.cempra.com ------urethritis Phase II completed www.cempra.com

SparVax™ PharmAthene anthrax Phase II recombinant protective antigen Annapolis, MD (pre- and post-exposure prevention) www.pharmathene.com (rPA) anthrax vaccine

SQ109 Sequella tuberculosis (Fast Track) Phase II (cell wall inhibitor) Rockville, MD www.sequella.com ORPHAN DRUG ------Helicobacter pylori infection Phase II www.sequella.com

Staphylococcus aureus recombinant GlaxoSmithKline Staphylococcus aureus infection Phase I conjugated vaccine Research Triangle Park, NC (prevention) www.gsk.com

Staphylococcus aureus vaccine Novartis Vaccines staphylococcal infection Phase I Cambridge, MA www.novartisvaccines.com

STP-206 live biotherapeutic Sigma-Tau Pharmaceuticals acute enterocolitis (prevention) Phase II Gaithersburg, MD www.sigmatau.com

streptococcal B vaccine conjugate Novartis Vaccines streptococcal group B infection Phase II Cambridge, MA (prevention) www.novartisvaccines.com

Streptococcus pneumoniae pediatric GlaxoSmithKline pneumococcal infection (prevention) Phase II next-generation recombinant Research Triangle Park, NC www.gsk.com conjugated vaccine

Streptococcus penumoniae vaccine Sano Pasteur meningitis, pneumonia Phase I Swiftwater, PA www.sano .com

surotomycin Cubist Pharmaceuticals Clostridium di cile-associated Phase III (CB-315) Lexington, MA diarrhea (Fast Track) www.cubist.com

Medicines in Development Infectious Diseases 2013 17 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

sutezolid Sequella tuberculosis Phase II ORPHAN DRUG Rockville, MD www.sequella.com

Taksta™ Cempra Pharmaceuticals chronic prosthetic joint infections, Phase II fusidic acid Chapel Hill, NC acute bacterial skin and soft tissue www.cempra.com ORPHAN DRUG infections

TD-1607 Theravance serious gram-positive infections Phase I (cell wall inhibitor) South San Francisco, CA www.theravance.com

TD-1792 Theravance serious gram-positive infections Phase II (cell wall inhibitor) South San Francisco, CA www.theravance.com

tedizolid phosphate Bayer HealthCare Pharmaceuticals acute bacterial skin and skin structure application submitted (TR-701) Whippany, NJ infections www.bayerpharma.com Cubist Pharmaceuticals www.cubist.com Lexington, MA ------hospital-acquired bacterial Phase II pneumonia, ventilator-associated www.bayerpharma.com bacterial pneumonia www.cubist.com

Thravixa™ Emergent BioSolutions anthrax Phase I fully human anthrax mAb Rockville, MD (Fast Track) www.emergentbiosolutions.com ORPHAN DRUG

tuberculosis recombinant subunit Sano Pasteur tuberculosis (prevention) Phase I vaccine Swiftwater, PA www.sano .com

tuberculosis vaccine Aeras tuberculosis (prevention) Phase II Rockville, MD www.aeras.org Crucell www.crucell.com Leiden, Netherlands

typhoid vaccine Novartis Vaccines typhoid (prevention) Phase II Cambridge, MA www.novartisvaccines.com

V114 Merck pneumococcal infection (prevention) Phase II (pneumococcal 15-valent Whitehouse Station, NJ www.merck.com conjugate vaccine)

Valortim® PharmAthene anthrax post-exposure (prevention Phase I anti-toxin mAb Annapolis, MD and treatment) (Fast Track) www.pharmathene.com ORPHAN DRUG

vancomycin inhalation powder Savara Pharmaceuticals MRSA Phase II ORPHAN DRUG Austin, TX www.savarapharma.com

18 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Bacterial Infections

Product Name Sponsor Indication Development Phase

VivaGel® Starpharma bacterial vaginosis (treatment) Phase III astodrimer Melbourne, Australia www.starpharma.com (SPL 7013) ------bacterial vaginosis (prevention) Phase II www.starpharma.com

VP 20621 ViroPharma Clostridium infection (prevention) Phase II (non-toxigenic strain of Exton, PA www.viropharma.com Clostridium di cile bacteria replacement)

WCK 771 Wockhardt MRSA Phase I Parsippany, NJ www.wockhardtusa.com

WCK 2349 Wockhardt MRSA Phase I Parsippany, NJ www.wockhardtusa.com

XF-73 Destiny Pharma post-surgical staphylococcal Phase II (cell membrane modulator) Brighton, United Kingdom infection (prevention) www.destinypharma.com National Institute of Allergy and www.niaid.nih.gov Infectious Diseases (NIAID) Bethesda, MD

XOMA 3AB XOMA botulism Phase I (botulism toxin inhibitor mAb) Berkeley, CA www.xoma.com National Institute of Allergy and www.niaid.nih.gov Infectious Diseases (NIAID) Bethesda, MD Fungal Infections

Product Name Sponsor Indication Development Phase

albaconazole Actavis fungal infections Phase II Parsippany, NJ www.actavis.com

amphotericin B liposomal oral Jina Pharmaceuticals mycoses in clinical trials Libertyville, IL www.jinapharma.com

AN2718 Anacor Pharmaceuticals mycoses, onychomycosis Phase I (leucyl-tRNA synthetase inhibitor) Palo Alto, CA www.anacor.com

antifungal vaccine Immunitor USA mycoses Phase I/II College Park, MD www.immunitor.com

Medicines in Development Infectious Diseases 2013 19 Medicines in Development for Infectious Diseases

Fungal Infections

Product Name Sponsor Indication Development Phase

econazole nitrate foam Quinnova Pharmaceuticals tinea pedis Phase III completed Jamison, PA www.quinnova.com

e naconazole topical Valeant Pharmaceuticals onychomycosis application submitted (IDP 108) Bridgewater, NJ www.valeant.com

isavuconazole Astellas Pharma US candidemia, invasive candidiasis, Phase III (azole antifungal) Northbrook, IL invasive aspergillosis (Fast Track) www.astellas.com ORPHAN DRUG Basilea Pharmaceutica Basel, Switzerland

luliconazole 1.3% Valeant Pharmaceuticals tinea corporis, tinea curis, tinea pedis application submitted Bridgewater, NJ www.valeant.com

luliconazole 10% Topica Pharmaceuticals onychomycosis Phase II/III Los Altos, CA www.topicapharma.com

ME1111 Meiji Seika Pharma onychomycosis Phase I (topical anti-fungal) Tokyo, Japan www.meiji-seika-pharma.co.jp

MGCD290 Mirati Therapeutics vulvovaginal candidiasis Phase II completed (HDAC fungal Hos2 inhibitor) San Diego, CA www.mirati.com

Mycamine® Astellas Pharma US candidiasis (neonates up to 120 days) Phase III micafungin Northbrook, IL www.astellas.com

MycoVa™ Apricus Biosciences onychomycosis Phase III terbina ne lacquer San Diego, CA www.apricusbio.com

NDV-3 NovaDigm Therapeutics recurrent vulvovaginal candidiasis Phase I/II (recombinant protein vaccine) Grand Forks, ND (prevention) www.novadigm.com

Noxa l® Merck mycoses (prevention) application submitted posaconazole Whitehouse Station, NJ www.merck.com (solid oral tablet)

PAC-113 Pacgen Life Science oral candidiasis Phase II Irvine, CA www.pacgen.com

SCY-078 Scynexis invasive fungal infections Phase II (glucan synthase inhibitor) Research Triangle Park, NC www.scynexis.com

SUBA™-itraconazole Mayne Pharma mycoses in clinical trials Salisbury, South Australia www.maynepharma.com

20 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Fungal Infections

Product Name Sponsor Indication Development Phase

T-2307 Fuji lm Pharmaceuticals U.S.A. mycoses Phase I Boston, MA www.toyama-chemical.co.jp Toyama Chemical Tokyo, Japan

tavaborole Anacor Pharmaceuticals onychomycosis application submitted Palo Alto, CA www.anacor.com

TDT 067 Celtic Pharma onychomycosis Phase III (terbina ne topical) Hamilton, Bermuda www.celticpharma.com

terbina ne iontophoretic NB Therapeutics onychomycosis Phase II Bristol, PA www.nitricbio.com

terbina ne transdermal Hisamitsu Pharmaceutical onychomycosis Phase II Tokyo, Japan www.hisamitsu.co.jp

VT-1161 Viamet Pharmaceuticals onychomycosis, vulvovaginal Phase II (14-alpha demethylase inhibitor) Durham, NC candidiasis www.viamet.com

Parasitic Infections

Product Name Sponsor Indication Development Phase

DeOvo™ Hatchtech pediculosis Phase II Ha44 topical Melbourne, Australia www.hatchtech.com.au

ferroquine Sano malaria (prevention) Phase II Bridgewater, NJ www.sano .com

KAE609 Novartis Pharmaceuticals malaria (treatment) Phase II East Hanover, NJ www.novartis.com

KAF156 Novartis Pharmaceuticals Plasmodium falciparum malaria, Phase I East Hanover, NJ Plasmodium vivax malaria www.novartis.com (treatment)

malaria vaccine GenVec Plasmodium falciparum malaria Phase I/II Gaithersburg, MD (prevention) www.genvec.com Naval Medical Research Center Silver Spring, MD

malaria vaccine Sanaria Plasmodium falciparum malaria Phase I/II (PfSPZ) Rockville, MD (prevention) www.sanaria.com

Medicines in Development Infectious Diseases 2013 21 Medicines in Development for Infectious Diseases

Parasitic Infections

Product Name Sponsor Indication Development Phase

malaria vaccine Crucell malaria (prevention) Phase I/II (recombinant, Ad35-CS) Leiden, Switzerland www.crucell.com

miltefosine Paladin Labs leishmaniasis application submitted ORPHAN DRUG Montreal, Canada www.paladin-labs.com

Mosquirix™ GlaxoSmithKline Plasmodium falciparum malaria Phase III malaria vaccine Research Triangle Park, NC (prevention) www.gsk.com (RTS,S)

nifurtimox Bayer HealthCare Pharmaceuticals Chagas disease Phase I ORPHAN DRUG Whippany, NJ www.bayerpharma.com

Nuartez™ Sigma-Tau Pharmaceuticals immediate treatment of severe and Phase III completed artesunate intravenous Gaithersburg, MD complicated P. falciparum malaria www.sigma-tau.com ORPHAN DRUG

Resultz® Piedmont Pharmaceuticals pediculosis Phase III isopropyl myristate Greensboro, NC www.piedmontpharma.com

tafenoquine GlaxoSmithKline Plasmodium vivax malaria Phase II ORPHAN DRUG Research Triangle Park, NC www.gsk.com Walter Reed Army Institute of Research Silver Spring, MD

visceral leishmaniasis vaccine Infectious Disease Research Institute visceral leishmaniasis Phase I Seattle, WA www.idri.org

zithromycin/chloroquine P zer malaria Phase III  xed-dose combination New York, NY www.p zer.com

Viral Infections

Product Name Sponsor Indication Development Phase

572-Trii ViiV Healthcare human immunode ciency virus (HIV) application submitted (dolutegravir+abacavir/ Research Triangle Park, NC infection www.viivhealthcare.com lamivudine)

ABT-450/r+ABT-267 AbbVie hepatitis C (genotype 1) Phase II (protease inhibitor/NS5A inhibitor) North Chicago, IL www.abbvie.com Enanta Pharmaceuticals www.enanta.com Watertown, MA

22 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

ABT-450/r+ABT-267+ribavirin AbbVie hepatitis C (genotype 1) Phase II (protease inhibitor/NS5A inhibitor/ North Chicago, IL www.abbvie.com ribavirin) Enanta Pharmaceuticals www.enanta.com Watertown, MA

ABT-450/r+ABT-267+ABT-333 AbbVie hepatitis C (genotype 1) Phase III (protease inhibitor/ NS5A inhibitor/ North Chicago, IL www.abbvie.com non-nucleoside inhibitor) Enanta Pharmaceuticals www.enanta.com Watertown, MA

ABT-450/r+ABT-267+ABT-333 AbbVie hepatitis C (genotype 1) Phase III +ribavirin North Chicago, IL (Breakthrough Therapy) www.abbvie.com (protease inhibitor/NS5A inhibitor/ Enanta Pharmaceuticals www.enanta.com non-nucleoside inhibitor/ribavirin) Watertown, MA

ABT-493+ABT-530 AbbVie hepatitis C Phase I (protease inhibitor/NS5A inhibitor) North Chicago, IL www.abbvie.com Enanta Pharmaceuticals www.enanta.com Watertown, MA

ACH-3102 Achillion Pharmaceuticals hepatitis C Phase II (NS5A inhibitor) New Haven, CT (Fast Track) www.achillion.com

AE-AI vaccine Antigen Express avian  u (prevention) Phase I Worcester, MA www.antigenexpress.com

AE-H vaccine Antigen Express HIV infection Phase I Worcester, MA (prevention and treatment) www.antigenexpress.com

A unov™ Novartis Vaccines in uenza A virus H5N1 subtype Phase II in uenza A virus H5N1 vaccine Cambridge, MA (prevention) www.novartisvaccines.com ( u cell culture)

AGS-004 Argos Therapeutics HIV-1 infection (treatment) Phase II (personalized dendritic cell-based Durham, NC www.argostherapeutics.com vaccine)

Alferon LDO® Hemispherx Biopharma viral infections Phase I/II interferon-alpha-n3 Philadelphia, PA www.hemispherx.net

ALNRSV01 Alnylam Pharmaceuticals respiratory syncytial virus (RSV) Phase II Cambridge, MA infection www.alnylam.com

ALS-8176 Alios BioPharma RSV infection Phase I South San Francisco, CA www.aliosbiopharma.com

Medicines in Development Infectious Diseases 2013 23 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

amdoxovir (DAPD) RFS Pharma HIV-1 infection Phase II Tucker, GA www.rfspharma.com

anti-PD-L1 Bristol-Myers Squibb viral infections Phase I Princeton, NJ www.bms.com

apricitabine Avexa HIV-1 infection (Fast Track) Phase III (ATC) Melbourne, Australia www.avexa.com.au Link Healthcare Warriewood, Australia

AR-101 Aridis Pharmaceuticals pneumonia Phase II (anti-Pa mAb) San Jose, CA www.aridispharma.com

ARC-520 Arrowhead Research hepatitis B Phase I (RNA interference) Pasadena, CA www.arrowheadresearch.com

Arestvyr™ SIGA Technologies orthopoxvirus infection Phase II tecovirimat New York, NY www.siga.com ORPHAN DRUG ------smallpox (Fast Track) Phase II www.siga.com

ASP0113 Astellas Pharma US cytomegalovirus (CMV) infection Phase III (cytomegalovirus DNA vaccine) Northbrook, IL (prevention) www.astellas.com ORPHAN DRUG

asunaprevir Bristol-Myers Squibb hepatitis C Phase III Princeton, NJ www.bms.com

atazanavir/cobicistat  xed-dose Bristol-Myers Squibb HIV-1 infection Phase I combination Princeton, NJ www.bms.com Gilead Sciences www.gilead.com Foster City, CA

AV4025 AllaChem hepatitis C Phase I (NS5A inhibitor) Hallandale Beach, FL www.allachem.com

AVI-7288 Sarepta Therapeutics Marburg virus disease Phase I (antisense oligonucleotide) Cambridge, MA (Fast Track) www.sareptatherapeutics.com ORPHAN DRUG

AVX101 AlphaVax HIV-1 infection (prevention) Phase I completed (monovalent HIV vaccine) Research Triangle Park, NC www.alphavax.com

24 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

AVX601 AlphaVax CMV infection (prevention) Phase I (cytomegalovirus vaccine) Research Triangle Park, NC www.alphavax.com Novartis Vaccines www.novartisvaccines.com Cambridge, MA

BAY 41-6551 Bayer HealthCare Pharmaceuticals gram-negative pneumonia Phase III (amikacin inhalation) Whippany, NJ (Fast Track) www.bayerpharma.com Nektar www.nektar.com San Francisco, CA ------nosocomial pneumonia Phase III (Fast Track) www.bayerpharma.com www.nektar.com

BMS-791325 Bristol-Myers Squibb hepatitis C Phase II (NS5B non-nucleoside inhibitor) Princeton, NJ www.bms.com

BMS-955176 Bristol-Myers Squibb HIV-1 infection Phase II Princeton, NJ www.bms.com

BMS-986001 Bristol-Myers Squibb HIV-1 infection Phase II (nucleoside reverse transcriptase Princeton, NJ www.bms.com inhibitor)

BTL-TML-HSV Beech Tree Labs recurrent oral herpes Phase II North Chester eld, VA www.beechtreelabs.com

BZF961 Novartis Pharmaceuticals hepatitis C Phase I/II East Hanover, NJ www.novartis.com

Cal-1-transduced hematopoietic Calimmune HIV-1 infection Phase I/II stem cell therapy Los Angeles, CA www.calimmune.com

CB5300 Canopus BioPharma hepatitis C Phase II Studio City, CA www.canopusbiopharma.com

cenicriviroc Tobira Therapeutics HIV-1 infection Phase II (CCR2/CCR5 receptor antagonist) South San Francisco, CA www.tobiratherapeutics.com

Medicines in Development Infectious Diseases 2013 25 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

Civacir® Biotest Pharmaceuticals hepatitis C in liver transplant patients Phase III hepatitis C immune globulin Boca Raton, FL (prevention) www.biotestpharma.com (human) ORPHAN DRUG

CMX001 Chimerix CMV infection (prevention) in Phase III (DNA-directed DNA polymerase Durham, NC transplant patients (Fast Track) www.chimerix.com inhibitor) ------adenovirus infection (prevention) Phase II (Fast Track) www.chimerix.com ------smallpox Phase I (Fast Track) www.chimerix.com

CMX157 Chimerix HIV infection Phase I (DNA-directed DNA polymerase Durham, NC www.chimerix.com inhibitor)

cobicistat Gilead Sciences HIV infection application submitted (Pk enhancer) Foster City, CA www.gilead.com

cobicistat/darunavir/emtricitabine/ Gilead Sciences HIV-1 infection Phase II tenofovir alafenamide  xed-dose Foster City, CA www.gilead.com combination Janssen Therapeutics www.janssentherapeutics.com Titusville, NJ

cobicistat/darunavir  xed-dose Gilead Sciences HIV-1 infection Phase III combination Foster City, CA www.gilead.com Janssen Therapeutics www.janssentherapeutics.com Titusville, NJ

cobicistat/elvitegravir/ Gilead Sciences HIV-1 infection Phase III emtricitabine/tenofovir Foster City, CA www.gilead.com alafenamide  xed-dose combination

CR6261 mAb CruCell in uenza A virus infection Phase I (in uenza vaccine) Leiden, Netherlands (treatment) www.crucell.com

CR8020 mAb CruCell in uenza A virus infection Phase I (in uenza virus hemagglutinin Leiden, Netherlands (prevention) www.crucell.com glycoprotein inhibitor)

Cytolin® CytoDyn HIV infection Phase I anti-CD8 mAb Lake Oswego, OR www.cytodyn.com

26 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

daclatasvir Bristol-Myers Squibb hepatitis C Phase III (NS5A protein inhibitor) Princeton, NJ www.bms.com

danoprevir Roche hepatitis C Phase II (RG7227) Nutley, NJ www.roche.com

dapivirine International Partnership for Microbicides HIV infection (prevention) Phase I/II (NNRTI) Silver Spring, MD www.ipmglobal.org

DCVax-001/CD-2401 Celldex Therapeutics HIV infection Phase I (recombinant protein vaccine) Needham, MA (prevention and treatment) www.celldextherapeutics.com Rockefeller University New York, NY

DEB025 Novartis Pharmaceuticals hepatitis C Phase III (alisporivir) East Hanover, NJ www.novartis.com

deleobuvir Boehringer Ingelheim Pharmaceuticals hepatitis C (combination therapy) Phase III (NS5 protein inhibitor) Ridge eld, CT www.boehringer-ingelheim.com

dengue DNA vaccine Naval Medical Research Center dengue (prevention) Phase I Silver Spring, MD www.vical.com Vical San Diego, CA

dengue fever vaccine Sano Pasteur mild to moderate dengue Phase III Swiftwater, PA (prevention) (Fast Track) www.sano .com

dengue vaccine GlaxoSmithKline dengue fever (prevention) Phase I (TDENV-PIV) Research Triangle Park, NC www.gsk.com Walter Reed Army Institute of Research Silver Spring, MD

DENVax™ Inviragen dengue (prevention) Phase II tetravalent hybrid dengue virus Fort Collins, CO www.inviragen.com vaccine

DermaVir™ Patch Genetic Immunity HIV-1 infection (treatment) Phase II DNA topical patch vaccine McLean, VA www.geneticimmunity.com

doravirine Merck HIV-1 infection (treatment) Phase II (MK-1439) Whitehouse Station, NJ www.merck.com

Medicines in Development Infectious Diseases 2013 27 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

DTP-HepB-Polio-Hib hexavalent Merck diphtheria, tetanus, pertussis, Phase III vaccine Whitehouse Station, NJ hepatitis B, poliomyelitis, www.merck.com (PRI51/V419) Sano Pasteur Haemophilus in uenzae type b www.sano .com Swiftwater, NJ (pediatric) (see also bacterial)

E-101 Exoxemis postoperative viral infections Phase III (antimicrobial topical liquid) Little Rock, AR (prevention) www.exoxemis.com (see also bacterial)

EBP921 Eiger BioPharmaceuticals hepatitis D Phase I (prenylation inhibitor) San Carlos, CA www.eigerbio.com

EBP994 Eiger BioPharmaceuticals hepatitis D Phase I San Carlos, CA www.eigerbio.com

EDP-239 Enanta Pharmaceuticals hepatitis C Phase I (NS5A inhibitor) Watertown, MA www.enanta.com Novartis Pharmaceuticals www.novartis.com East Hanover, NJ

Edurant® Janssen Therapeutics HIV-1 infection (adolescents) Phase II rilpivirine Titusville, NJ www.janssentherapeutics.com

efavirenz/lamivudine/tenofovir Mylan Laboratories HIV-1 infection (treatment) application submitted fumarate  xed-dose combination Canonsburg, PA www.mylan.com

EISO ointment ViroXis viral infections Phase II (sandalwood oil therapeutic) San Antonio, TX www.viroxis.com

elvitegravir Gilead Sciences HIV-1 infection (treatment) application submitted (integrase inhibitor) Foster City, CA www.gilead.com

faldaprevir Boehringer Ingelheim Pharmaceuticals hepatitis C (combination therapy) Phase III (NS3 protein inhibitor) Ridge eld, CT (Fast Track) www.boehringer-ingelheim.com

favipiravir BioDefense Therapeutics in uenza virus infection (treatment) Phase II (Department of Defense) www.medivector.com Fort Belvoir, VA MediVector Boston, MA

FGI-101-1A6 Functional Genetics viral infections Phase I (mAb targeting tumor Gaithersburg, MD www.functional-genetics.com susceptibility gene 101)

28 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

Fluad® Novartis Vaccines in uenza virus infection (prevention) Phase III in uenza virus vaccine Cambridge, MA (children and elderly) www.novartisvaccines.com (H1N1/H3N2/type B strains)

Flucelvax® Novartis Vaccines in uenza virus infection Phase III in uenza virus vaccine Cambridge, MA (pediatric prevention) www.novartisvaccines.com

 u rvitide-3 nasal spray Autoimmune Technologies in uenza virus infection Phase I vaccine New Orleans, LA www.autoimmune.com

Fluzone® QIV ID Sano Pasteur in uenza virus infection (prevention) Phase III quadrivalent inactivated in uenza Swiftwater, PA www.sano .com vaccine intradermal

FST-100 Foresight Biotherapeutics adenoviral conjunctivitis Phase II (povidone iodine/dexamethasone) New York, NY www.foresightbiotherapeutics.com

GelVac™ Nanotherapeutics in uenza virus infection Phase I H5N1 in uenza virus vaccine-nasal Alachua, FL www.nanotherapeutics.com dry powder

GEN-003 Genocea Biosciences HSV type 2 infection (treatment) Phase I/II (HSV type-2 therapeutic vaccine) Cambridge, MA www.genocea.com

GI-5005 GlobeImmune hepatitis C Phase II (tarmogen T-cell immunity Louisville, CO www.globeimmune.com stimulator)

GS-4774 Gilead Sciences hepatitis B Phase II (tarmogen T-cell immunity Foster City, CA www.gilead.com stimulator) GlobeImmune www.globeimmune.com Louisville, CO

GS-5806 Gilead Sciences RSV infection Phase II Foster City, CA www.gilead.com

GS-5816 Gilead Sciences hepatitis C Phase II (pan-genotypic NS5A inhibitor) Foster City, CA www.gilead.com

GS-9620 Gilead Sciences hepatitis B Phase I (TLR-7 agonist) Foster City, CA www.gilead.com

GS-9669 Gilead Sciences hepatitis C Phase II (non-nucleoside NS5B inhibitor) Foster City, CA www.gilead.com

GSK2336805 Janssen Research & Development hepatitis C Phase II (NS5A inhibitor) Raritan, NJ www.janssenrnd.com

Medicines in Development Infectious Diseases 2013 29 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

GSK2654909A GlaxoSmithKline H9N2 in uenza A virus infection Phase I (immunostimulant vaccine) Research Triangle Park, NC (prevention) www.gsk.com

GSK2654911A GlaxoSmithKline H9N2 in uenza A virus infection Phase I (immunostimulant vaccine) Research Triangle Park, NC (prevention) www.gsk.com

GSK2838497A GlaxoSmithKline non-typeable Haemophilus in uenzae Phase I (NTHi vaccine) Research Triangle Park, NC (prevention) www.gsk.com

GSK3003891A GlaxoSmithKline RSV infection (prevention) Phase I (immunostimulant vaccine) Research Triangle Park, NC www.gsk.com

Hanferon™ HanAll Biopharma hepatitis C Phase II interferon alpha-2b Seoul, South Korea www.hanallbiopharma.com

HBV-002 Hawaii Biotech West Nile virus infection (prevention) Phase I completed (recombinant subunit vaccine) Aiea, HI www.hibiotech.com

hepatitis C vaccine therapy GlaxoSmithKline hepatitis C (prevention) Phase I/II (Ad6NSmut) Research Triangle Park, NC www.gsk.com

Heplisav™ Dynavax hepatitis B (prevention) application submitted hepatitis B vaccine 1018-ISS Berkeley, CA www.dynavax.com conjugate

HerpV Agenus HSV type 2 infection (treatment) Phase II herpes simplex vaccine Lexington, MA www.agenusbio.com

HIV attachment inhibitor Bristol-Myers Squibb HIV-1 infection treatment Phase II Princeton, NJ www.bms.com

HIVAX™ GeneCure Biotechnologies HIV-1 infection Phase I replication-defective HIV-1 vaccine Norcross, GA www.genecure.com

HIV gene therapy Adaptimmune HIV infection (treatment) Phase I Philadelphia, PA www.adaptimmune.com University of Pennsylvania Philadelphia, PA

HIV gene therapy Calimmune HIV infection Phase I/II Los Angeles, CA www.calimmune.com

HIV MAG pDNA vaccine Profectus BioSciences HIV-1 infection (prevention) Phase I Baltimore, MD www.profectusbiosciences.com ------HIV-1 infection (treatment) Phase I www.profectusbiosciences.com

30 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

HIV recombinant vaccine GlaxoSmithKline HIV disease immunotherapy Phase II Research Triangle Park, NC www.gsk.com

HIV recombinant vaccine GlaxoSmithKline HIV infection (prevention) Phase I Research Triangle Park, NC www.gsk.com

HIV vaccine Crucell HIV infection (prevention) Phase I Leiden, Netherlands www.crucell.com Beth Israel Deaconess Medical Center Boston, MA International AIDS Vaccine Initiative New York, NY

HIV vaccine GeoVax Labs HIV infection (prevention) Phase II Atlanta, GA www.geovax.com

HIV vaccine GeoVax Labs HIV infection (treatment) Phase I/II Atlanta, GA www.geovax.com

HIV vaccine Novartis Vaccines HIV infection Phase I Cambridge, MA www.novartisvaccines.com

HIV vaccine PaxVax HIV infection (prevention) Phase I San Diego, CA www.paxvax.com

HIV vaccine Profectus Biosciences HIV infection (prevention) Phase I (rVSV) Baltimore, MD www.profectusbiosciences.com

HIV-1 gene therapy Takara Bio HIV-1 infection Phase I Tokyo, Japan www.takara-bio.com

HSV-2 vaccine National Institute of Allergy and herpes simplex virus (HSV) infection Phase I Infectious Diseases (NIAID) www.sano .com Bethesda, MD Sano Pasteur Swiftwater, PA

ibalizumab TaiMed Biologics USA HIV-1 infection (treatment) Phase II (TMB-355) Irvine, CA (Fast Track) www.taimedbiologics.com

IC31/trivaleant in uenza vaccine Novartis Vaccines in uenza virus infection Phase I Cambridge, MA www.novartisvaccines.com Valneva Vienna, Austria

Medicines in Development Infectious Diseases 2013 31 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

IDX719 Idenix Pharmaceuticals hepatitis C Phase II (NS5A protein inhibitor) Cambridge, MA (Fast Track) www.idenix.com

Imvamune® Bavarian Nordic smallpox (prevention) Phase III smallpox vaccine Mountain View, CA (liquid formulation) www.bavarian-nordic.com ------smallpox (prevention) Phase II (freeze-dried formulation) www.bavarian-nordic.com

Incivek® Vertex Pharmaceuticals hepatitis C (pediatric) Phase I/II telaprevir Cambridge, MA www.vrtx.com

in uenza A virus H1N1 seasonal Vaxart in uenza A virus H1N1 subtype Phase I vaccine San Francisco, CA (prevention) www.vaxart.com

in uenza A virus H1N1 vaccine iBio in uenza A virus H1N1 subtype Phase I Newark, DE (prevention) www.ibioinc.com

in uenza A virus H1N1 vaccine Medicago USA in uenza A virus H1N1 subtype Phase I Durham, NC (prevention) www.medicago.com

in uenza A virus H1N1 vaccine CEL-SCI in uenza A virus H1N1 subtype Phase I (L.E.A.P.S.™) Vienna, VA (prevention and treatment) www.cel-sci.com

in uenza A virus H3N2 vaccine Novartis Vaccines in uenza A virus H3N2 subtype Phase I Cambridge, MA (prevention) www.novartisvaccines.com

in uenza A virus H5N1 cell GlaxoSmithKline in uenza A virus H5N1 subtype Phase I culture-based Research Triangle Park, NC (prevention for pandemic use) www.gsk.com

in uenza A virus H5N1 vaccine Baxter Healthcare in uenza A virus H5N1 subtype Phase I Deer eld, IL (prevention) www.baxter.com

in uenza A virus H5N1 vaccine iBio in uenza A virus H5N1 subtype Phase I Newark, DE (prevention) www.ibioinc.com

in uenza A virus H5N1 vaccine Medicago USA in uenza A virus H5N1 subtype Phase I Durham, NC (prevention) www.medicago.com

in uenza A virus H5N1 vaccine Vaxart in uenza A virus H5N1 subtype Phase I San Francisco, CA (prevention) www.vaxart.com

in uenza A virus H5N1 vaccine Novavax in uenza A virus H5N1 subtype Phase II (recombinant VLP vaccine) Rockville, MD (prevention) www.novavax.com (seasonal use) ------in uenza A virus H5N1 subtype Phase I (prevention) www.novavax.com (pandemic use)

32 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

in uenza A virus H7N1 vaccine GlaxoSmithKline in uenza A virus H7N1 subtype Phase I Research Triangle Park, NC (prevention) www.gsk.com

in uenza A virus H7N9 vaccine Novavax in uenza A virus H7N9 subtype Phase I Rockville, MD (prevention) www.novavax.com

in uenza A virus H9N2 vaccine Baxter Healthcare in uenza A virus H9N2 subtype Phase I/II completed Deer eld, IL (prevention) www.baxter.com

in uenza vaccine (seasonal) Inovio Pharmaceuticals in uenza (prevention) Phase I Blue Bell, PA (ages 18 – 55 years) www.inovio.com

in uenza vaccine (seasonal) Inovio Pharmaceuticals in uenza (prevention) Phase I Blue Bell, PA (ages 65 and older) www.inovio.com

in uenza virus H5N1 GlaxoSmithKline in uenza A virus H5N1 subtype application submitted (pre-) pandemic vaccine Research Triangle Park, NC (prevention) www.gsk.com (pandemic use in adults) ------in uenza A virus H5N1 subtype Phase III (prevention) www.gsk.com (pediatric pandemic use)

INO-8000 Inovio Pharmaceuticals hepatitis C (genotype 1) Phase I (synthetic multi-antigen DNA Blue Bell, PA www.inovio.com vaccine)

INV21 Inviragen hand, foot and mouth disease Phase I (enterovirus A vaccine) Fort Collins, CO (prevention) www.inviragen.com

IRT-103 TNI BioTech HIV infection Phase II (low dose naltrexone) Bethesda, MD www.tnibiotech.com

ITV-1 Immunotech Laboratories HIV infection (salvage therapy) Phase I (immune therapeutic vaccine) Monrovia, CA www.immunotechlab.com

ITX 5061 iTherx hepatitis C in liver transplant patients Phase II (virus internalization inhibitor) San Diego, CA www.itherx.com

JNJ-47910382 Janssen Research & Development hepatitis C Phase I Raritan, NJ www.janssenrnd.com

KamRAB® Kamada rabies (prevention) Phase III rabies immune globulin Ness Ziona, Israel www.kamada.com Kedrion Biopharma www.kedrionusa.com Fort Lee, NJ

KP-1461 Koronis Pharmaceuticals HIV infection (treatment) Phase II (replication inhibitor) Seattle, WA www.koronispharma.com

Medicines in Development Infectious Diseases 2013 33 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

lamivudine/nevirapine/zidovudine Elim Pediatric Pharmaceuticals HIV infection (treatment) Phase I  xed-dose combination Rolling Meadows, IL (pediatric) www.elimpedpharma.com

laninamivir octanoate Biota Pharmaceuticals in uenza virus infection (treatment) Phase II (CS-8958) Alpharetta, GA www.biotapharma.com Daiichi Sankyo Tokyo, Japan

LIQ-001 Liquidia Technologies in uenza virus infection (prevention) Phase I completed (adjuvant in uenza virus vaccine) Research Triangle Park, NC www.liquidia.com

lomibuvir Vertex Pharmaceuticals hepatitis C Phase II (VX-222) Cambridge, MA www.vrtx.com

low-dose oral interferon Amarillo Biosciences hepatitis C Phase II Amarillo, TX www.amarbio.com

maribavir ViroPharma resistant/refractory CMV infection in Phase II ORPHAN DRUG Exton, PA transplant patients (prevention) www.viropharma.com (Fast Track)

MBL-HCV1 MassBiologics hepatitis C Phase II Boston, MA www.umassmed.edu/massbiologics

MBX-400/cyclopropavir Microbiotix CMV infection (treatment) Phase I (nucleoside reverse transcriptase Worcester, MA www.microbiotix.com inhibitor/virus replication inhibitor) ORPHAN DRUG

MBX-700 Microbiotix hepatitis C Phase I (NS5B inhibitor) Worcester, MA www.microbiotix.com

MDT-637 MicroDose Therapeutx RSV infection Phase I (viral fusion protein inhibitor) Monmouth Junction, NJ www.mdtx.com

MEDI-550 MedImmune pandemic in uenza (prevention) Phase I (H5N1 avian in uenza vaccine Gaithersburg, MD www.medimmune.com intranasal)

miravirsen Santaris Pharma A/S USA hepatitis C (treatment) Phase II (MIRN122 microRNA inhibitor) San Diego, CA www.santaris.com

MK-5172 Merck hepatitis C Phase II (HCV NS3/NS4 protein inhibitor) Whitehouse Station, NJ www.merck.com

MK-6325 Merck hepatitis C Phase I completed Whitehouse Station, NJ www.merck.com

34 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

MK-8228 AiCuris CMV infection (prevention) Phase II (letermovir) Wuppertal, Germany (Fast Track) www.merck.com ORPHAN DRUG Merck Whitehouse Station, NJ

MK-8742 Merck hepatitis C Phase II (NS5 protein inhibitor) Whitehouse Station, NJ www.merck.com

MMR vaccine GlaxoSmithKline measles, mumps, rubella Phase III (live attenuated trivalent vaccine) Research Triangle Park, NC www.gsk.com (GSK209762)

Nabi-HB® Biotest Pharmaceuticals hepatitis B virus reinfection in liver application submitted hepatitis B immune globulin Boca Raton, FL transplant patients (prevention) www.biotestpharma.com (human) ORPHAN DRUG

NB-001 NanoBio recurrent herpes labialis Phase III (nanoemulsion) Ann Arbor, MI www.nanobio.com

NB-1008 NanoBio seasonal in uenza virus (prevention) Phase I (intranasal vaccine) Ann Arbor, MI www.nanobio.com

neceprevir/ACH-2684 Achillion Pharmaceuticals hepatitis C Phase I (protease inhibitor) New Haven, CT www.achillion.com

nitazoxanide Romark Laboratories acute uncomplicated in uenza Phase II/III Tampa, FL (NT-300) www.romark.com ------hepatitis C Phase II/III (NT-675) www.romark.com

norovirus bivalent vaccine LigoCyte Pharmaceuticals (Takeda) norovirus infection (prevention) Phase I/II Bozeman, MT www.takeda.com

NU300 Nuron Biotech Haemophilus in uenzae type b Phase II (Hib CRM 197 conjugate vaccine) Exton, PA infection (prevention) (pediatric) www.nuronbiotech.com

oseltamivir intravenous Roche in uenza virus infection Phase III completed Nutley, NJ www.roche.com

PanBlok® Protein Sciences in uenza A virus H5N1 subtype Phase I/II in uenza A virus H5N1 vaccine Meridian, CT (prevention) www.proteinsciences.com

Medicines in Development Infectious Diseases 2013 35 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

PEGinterferon lambda-1a Bristol-Myers Squibb hepatitis C Phase III Princeton, NJ www.bms.com

PEG-Intron A® Merck hepatitis B Phase III peginterferon alfa-2b Whitehouse Station, NJ www.merck.com

PENNVAX™-B Inovio Pharmaceuticals HIV infection Phase I DNA vaccine (clade B) Blue Bell, PA (prevention and treatment) www.inovio.com

PENNVAX™-G Inovio Pharmaceuticals HIV infection Phase I DNA vaccine (clade A, C, D) Blue Bell, PA (prevention and treatment) www.inovio.com

peramivir BioCryst Pharmaceuticals seasonal in uenza Phase III Durham, NC (Fast Track) www.biocryst.com

PER.C- u vaccine Crucell in uenza virus infection (prevention) Phase II Leiden, Netherlands www.crucell.com

PPI-383 Presidio Pharmaceuticals hepatitis C Phase I (NS5B protein inhibitor) San Francisco, CA www.presidiopharma.com

PPI-668 Presidio Pharmaceuticals hepatitis C Phase II (NS5A protein inhibitor) San Francisco, CA www.presidiopharma.com

Pre ucel™ Baxter Healthcare in uenza virus infection (prevention) Phase III seasonal in uenza virus vaccine Deer eld, IL www.baxter.com

PRVV MedImmune RSV infection (infants) (prevention) Phase I (MEDI-559) Gaithersburg, MD www.medimmune.com

PXVX-0103 PaxVax in uenza A virus H5N1 subtype Phase I (in uenza A virus H5N1 vaccine) San Diego, CA (prevention) www.paxvax.com

Quadracel® Sano Pasteur diphtheria, tetanus, pertussis and Phase III diphtheria and tetanus toxoids Swiftwater, PA polio vaccine (in children 4 – 6 years www.sano .com and acellular pertussis vaccine of age) adsorbed combined with (see also bacterial) inactivated poliomyelitis vaccine

rabies VRVg Sano Pasteur rabies (prevention) Phase II (puri ed vero rabies vaccine) Swiftwater, PA www.sano .com

radavirsen Sarepta Therapeutics in uenza A virus infection Phase I (AVI-7000) Cambridge, MA www.sareptatherapeutics.com

36 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

RAP101 RAPID Pharmaceuticals HIV infection Phase II (CCR5 receptor antagonist) Huenenberg, Switzerland www.rapidpharma.com

Relenza® IV GlaxoSmithKline in uenza Phase III zanamivir i.v. Research Triangle Park, NC www.gsk.com

respiratory syncytial virus Novavax RSV infection (prevention) Phase II recombinant nanoparticle vaccine Rockville, MD www.novavax.com

RG7128 Roche hepatitis C Phase II (mericitabine) Nutley, NJ www.roche.com

RG7667 Genentech CMV infection (prevention) in kidney Phase II (intravenous) South San Francisco, CA transplant patients www.gene.com

RI-002 ADMA Biologics respiratory tract infections Phase III (immune globulin intravenous) Ramsey, NJ (prevention) in patients with primary www.admabiologics.com immune de ciency disease (PIDD)

rotavirus oral vaccine Sano Pasteur rotavirus infection (prevention) Phase II (live attenuated tetravalent) Swiftwater, PA www.sano .com

SAV001 Sumagen HIV-1 infection Phase I (genetically attenuated, irradiated Seoul, South Korea www.sumagen.co.kr and chemically inactivated HIV vaccine)

SB-728-T Sangamo BioSciences HIV infection Phase II (CCR5 receptor modulator) Richmond, CA www.sangamo.com

SB9200 Spring Bank Pharmaceuticals hepatitis B, hepatitis C Phase I (small molecule nucleic acid Milford, MA www.springbankpharm.com hybrid)

SCY-635 Scynexis hepatitis C Phase II (cyclophilin inhibitor) Research Triangle Park, NC www.scynexis.com

setrobuvir Roche hepatitis C (Fast Track) Phase II (RG7790) Nutley, NJ www.roche.com

S/GSK1265744 ViiV Healthcare HIV infection Phase II (integrase inhibitor) Research Triangle Park, NC www.viivhealthcare.com

sofosbuvir Gilead Sciences hepatitis C (Fast Track) application submitted Foster City, CA (treatment naïve, treatment www.gilead.com experienced)

Medicines in Development Infectious Diseases 2013 37 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

sofosbuvir/ledipasvir  xed-dose Gilead Sciences hepatitis C (treatment) Phase III combination (nucleotide NS5B Foster City, CA www.gilead.com inhibitor/NS5A inhibitor)

sovaprevir Achillion Pharmaceuticals hepatitis C (Fast Track) Phase II (HCV protease inhibitor) New Haven, CT www.achillion.com

TBR-220 Tobira Therapeutics HIV-1 infection Phase I (CCR5 receptor antagonist) South San Francisco, CA www.tobiratherapeutics.com

TCN-032 Theraclone Sciences in uenza A virus infection Phase II (M2e protein inhibitor) Seattle, WA www.theraclone-sciences.com

TCN-202 Theraclone Sciences CMV infection (prevention) Phase I (simplex virus glycoprotein Seattle, WA www.theraclone-sciences.com B inhibitor) ORPHAN DRUG

tenofovir alafenamide Gilead Sciences hepatitis B, HIV infection Phase III (nucleotide reverse transcriptase Foster City, CA www.gilead.com inhibitor)

tenofovir gel CONRAD HIV infection (prevention) Phase I (vaginal) Arlington, VA www.conrad.org

TG-2349 TaiGen Biotechnology hepatitis C Phase II (HCV NS3/4A protease inhibitor) Taipei, Taiwan www.taigenbiotech.com.tw

TG-4040 Transgene hepatitis C Phase II (vector-based therapeutic vaccine) Rockville, MD www.transgene.fr

TKM-Ebola Tekmira Pharmaceuticals Ebola virus infection (therapeutic) Phase I Burnaby, Canada www.tekmira.com Department of Defense Washington, DC

TMC-310911 Janssen Research & Development HIV-1 infection Phase II (HIV protease inhibitor) Raritan, NJ www.janssenrnd.com

TMC-647055 Janssen Research & Development hepatitis C Phase II (NS5 protein inhibitor) Raritan, NJ www.janssenrnd.com

UB-421 United Biomedical HIV-1 infection Phase II (HIV fusion inhibitor) Hauppauge, NY www.unitedbiomedical.com

38 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

V180 Merck dengue (prevention) Phase I (dengue subunit vaccine) Whitehouse Station, NJ www.merck.com

V212 Merck herpes zoster (prevention) Phase III (heat-treated varicella zoster virus Whitehouse Station, NJ www.merck.com [VZV] vaccine)

V503 Merck human papillomavirus (HPV) Phase III (virus-like particle [VLP] vaccine) Whitehouse Station, NJ infection (prevention and www.merck.com treatment)

Vacc-4x Bionor Pharma HIV-1 infection Phase II (intradermal vaccine) Oslo, Norway www.bionorpharma.com

vaniprevir Merck hepatitis C Phase III (MK-7009) Whitehouse Station, NJ www.merck.com

vapendavir Biota Pharmaceuticals rhinovirus infection Phase II Alpharetta, GA www.biotapharma.com

varicella zoster recombinant GlaxoSmithKline herpes zoster (prevention) Phase III vaccine Research Triangle Park, NC www.gsk.com

varicella zoster virus vaccine live Merck herpes zoster Phase I completed (intradermal) Whitehouse Station, NJ www.merck.com

VAX-102 VaxInnate seasonal in uenza A virus infection Phase I/II (Flagellin.HuM2e) Cranbury, NJ www.vaxinnate.com

VAX-125 VaxInnate pandemic in uenza A virus infection Phase II complete (Flagellin.HuHA) Cranbury, NJ www.vaxinnate.com

VAX-128 VaxInnate pandemic in uenza A virus H1N1 Phase I (recombinant vaccine) Cranbury, NJ subtype (prevention) www.vaxinnate.com

VAX-161 VaxInnate pandemic in uenza A virus H5N1 Phase I (recombinant vaccine) Cranbury, NJ subtype (prevention) www.vaxinnate.com

vedroprevir Gilead Sciences hepatitis C Phase II (GS-9451) Foster City, CA www.gilead.com

VGX-3100 Inovio Pharmaceuticals HPV infection Phase II (HPV type 16/18 DNA vaccine) Blue Bell, PA www.inovio.com

Medicines in Development Infectious Diseases 2013 39 Medicines in Development for Infectious Diseases

Viral Infections

Product Name Sponsor Indication Development Phase

VGX-3400 Inovio Pharmaceuticals in uenza A virus H5N1 subtype Phase I (DNA vaccine) Blue Bell, PA (prevention) www.inovio.com

VRC-HIVADV014-00-VP GenVec HIV infection (prevention) Phase II completed (HIV-1 recombinant adenovirus Gaithersburg, MD www.genvec.com vaccine) Vaccine Research Center (NIAID) www.vrc.nih.gov Bethesda, MD

VRC-HIVADV027-00-VP GenVec HIV-1 infection (prevention) Phase I (HIV adenovector Ad35 vaccine) Gaithersburg, MD www.genvec.com Vaccine Research Center (NIAID) www.vrc.nih.gov Bethesda, MD

VRC-HIVDNA016-00-VP Vaccine Research Center (NIAID) HIV infection (prevention) Phase I (HIV DNA vaccine) Bethesda, MD www.vrc.nih.gov

VX-135 Vertex Pharmaceuticals hepatitis C Phase II (NS5B protein inhibitor) Cambridge, MA www.vrtx.com

VX-787 Vertex Pharmaceuticals in uenza A virus infection Phase II (viral protein inhibitor) Cambridge, MA www.vrtx.com

Xerese® Meda Pharmaceuticals herpes labialis (6 – 11 years of age) Phase III completed aciclovir and hydrocortisone cream Somerset, NJ www.meda.us Valeant Pharmaceuticals www.valeant.com Bridgewater, NJ

Other

Product Name Sponsor Indication Development Phase

ALT 005 Altacor ophthalmic infections secondary to Phase III Cambridge, United Kingdom ocular surgery (prevention) www.altacor-pharma.com

Cytorex-EBV Cell Medica malignancies associated with Phase I/II (cell therapy) London, United Kingdom oncogenic Epstein-Barr virus www.cellmedica.co.uk Center for Gene and Cell Therapy at (treatment) Baylor College of Medicine Houston, TX

40 Medicines in Development Infectious Diseases 2013 Medicines in Development for Infectious Diseases

Other

Product Name Sponsor Indication Development Phase

Duac Low Dose Stiefel Laboratories (GSK) acne vulgaris application submitted clindamycin/benzoyl peroxide gel Research Triangle Park, NC www.gsk.com

FST-201 Foresight Biotherapeutics otitis externa Phase III (povidone iodine/dexamethasone New York, NY www.foresightbiotherapeutics.com otic suspension)

GC5101B Green Cross infections Phase III (immune globulin intravenous) Yongin, South Korea www.greencross.com

INTERCEPT Blood System Cerus inactivation of pathogens in blood Phase II for red blood cells combined with Concord, CA intended for transfusions www.cerus.com amustaline

RG7745 Genentech infections Phase I South San Francisco, CA www.gene.com

sarecycline Warner Chilcott (Actavis) acne vulgaris Phase II (narrow-spectrum tetracycline) Parsippany, NJ www.actavis.com

The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” database based on the latest information. Report current as of November 22, 2013. 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 © 2013 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 Infectious Diseases 2013 41 Glossary

acne vulgaris—The common form of Chagas disease—A tropical parasitic and Drug Administration. The purpose acne seen most often in teenagers or disease caused by Trypanosoma cruzi, is to get important new drugs to the young adults, which is the result of over- commonly transmitted to humans and patient earlier. Fast Track addresses a active oil glands that become plugged, other mammals by infected insects. The broad range of serious diseases. Gener- red, and infl amed. Most outbreaks of disease may also be spread through ally, determining factors include whether acne can be treated by keeping the skin blood transfusion and organ transplan- the drug will have an impact on such clear and avoiding irritating soaps, foods, tation, ingestion of food contaminated factors as survival, day-to-day function- drinks, and cosmetics. Severe acne and with parasites, and from a mother to ing, or the likelihood that the disease, if acne in those who are prone to scarring her fetus. left untreated, will progress from a less can be treated with topical creams and severe condition to a more serious one. anti-infl ammatory medications. Clostridium diffi cile—A bacterium that Filling an unmet medical need is defi ned produces an irritating toxin that causes a as providing a therapy where none exists Anthrax—An infectious disease caused form of colitis characterized by profuse, or providing a therapy which may be by a type of bacteria called Bacillus watery diarrhea with cramps and low- potentially superior to existing therapy. anthracis. Infection in humans most grade fever. Once a drug receives Fast Track designa- often involves the skin, gastrointestinal tion, early and frequent communication cytomegalovirus (CMV)—An opportu- tract, or lungs. between the FDA and a drug company is nistic infection that affl icts people whose encouraged throughout the entire drug application submitted—An application immune systems are weak, such as AIDS development and review process. The for marketing that has been submitted patients, and can be fatal. frequency of communication assures that to the Food and Drug Administration questions and issues are resolved quickly, (FDA). The application can either be an diphtheria—A bacterial infection charac- often leading to earlier drug approval NDA (new drug application) or a BLA terized by mucus coating the membranes and access by patients. (biologic license application). of the nose and throat, causing breath- ing problems, a fever, sore throat, vomit- gram-positive/negative bacteria— aspergillosis—Infection caused by ing, stomach pains, and chills. Gram’s stain is a method of staining Aspergillus fumigatus, a fungus found in bacteria in order to identify them. old buildings or decaying plant matter. Ebola virus—The cause of Ebola hemor- rhagic (bloody) fever, a severe, often Gram-positive bacteria stain violet; bacteremia—Presence of bacteria in the fatal disease in humans and nonhuman gram-negative bacteria stain red. bloodstream. primates (monkeys, gorillas, and chim- —A type of panzees). Researchers believe that the Haemophilus infl uenzae bacteria found in the respiratory tract that botulism—A severe, sometimes fatal virus is animal-borne (zoonotic) and is causes acute respiratory infections and food poisoning caused by ingestion of normally maintained in an animal host meningitis in children, but rarely in adults. food containing botulin and characterized that is native to the African continent. by nausea, vomiting, disturbed vision, helicobacter infections—Caused by muscular weakness, and fatigue. enterococcal infections—Caused by a Helicobacter pylori, a bacterium that is Streptococcus bacterium normally pres- commonly found in the stomach. It is bronchiectasis—An irreversible widening ent in the human intestine. It can cause present in approximately one-half of the (dilation) of portions of the bronchi result- infections during or after surgery. ing from damage to the bronchial wall. world’s population. The vast majority of Escherichia coli (E. coli)—A common people infected with H. pylori have no Campylobacter infections—Infections bacteria that is a cause of traveler’s symptoms and will never develop prob- caused by the Campylobacter organism, diarrhea. Certain strains of E. coli infect lems; however, H. pylori is capable of which is actually a group of spiral-shaped the large intestine and produce serious causing a number of digestive problems, bacteria that can cause disease in hu- complications. including ulcers, and much less common- mans and animals. Campylobacter is one ly, stomach cancer. It is not clear why of the most common bacterial causes of Fast Track—A process designed to some people with H. pylori get these diarrheal illness in the United States. facilitate the development and expedite conditions and others do not. the review of drugs to treat serious candidiasis—A fungal infection, caused diseases and fi ll an unmet medical need. hepatitis—Infl ammation of the liver by Candida albicans, usually of the The status is assigned by the U.S. Food with accompanying liver cell damage or moist cutaneous areas of the body.

42 Medicines in Development Infectious Diseases 2013 Glossary

death, caused most often by viral infec- arise constantly throughout the world. infection that can destroy the muscles, tion, e.g., hepatitis A, B and C. skin, and underlying tissue. The word leishmaniasis—Diseases affecting skin “necrotizing” refers to something that herpes simplex—Herpes simplex virus 1 (cutaneous), mucous membranes and causes body tissue to die. causes cold sores or fever blisters on the internal organs (visceral) caused by a mouth or around the eyes and can be parasite called Leishmania, which is Neisseria meningitidis—The gram- transmitted to the genital area. Herpes transmitted from infected animals or negative bacterium that causes menin- simplex 2 causes painful sores of the people to new hosts by sand fl ies. gococcal meningitis in humans, the only anus or genitals. natural hosts in which it causes disease. malaria—A serious parasitic disease, Meningococci enter the nasal passage herpes varicella zoster virus (HVZ)— spread by the bite of the Anopheles and may cause no symptoms (up to 30 Also called shingles, consists of very mosquito. Malaria is characterized by percent of the population may harbor painful blisters on the skin and affects severe fever and chills and complications them between epidemics), or they may areas innervated by specifi c nerves. It affecting the kidneys, liver, brain and enter the bloodstream and produce the may appear in adulthood as a result of blood. symptoms of meningitis. having had chicken pox (caused by the varicella virus) as a child. Marburg virus disease—Also called noroviruses—A group of viruses that Marburg hemorrhagic fever, a rare, cause the “stomach fl u,” or gastro- HIV infection—The presence of severe type of hemorrhagic fever that enteritis. Symptoms usually include antibodies in the blood to the human affects both humans and nonhuman nausea, vomiting, diarrhea, and some immunodefi ciency virus (the virus that primates. It is caused by a genetically stomach cramping. Sometimes people causes AIDS). HIV-1 refers to the most unique animal-borne (zoonotic) RNA vi- also have a low-grade fever, chills, common strain of the virus found in rus of the fi lovirus family. Marburg virus headache, muscle aches, and fatigue. U.S. AIDS patients. is indigenous to Africa, including parts The illness often begins suddenly and of Uganda, Western Kenya, and perhaps lasts for one or two days. human papillomavirus (HPV)—Viral Zimbabwe. agent of warts, believed to be conta- nosocomial—Refers to infections that gious and mostly harmless, affecting meningococcal infections—Caused by have been caught in a hospital. only the skin’s topmost layer. the bacterium Neisseria meningitidis (also termed meningococcus). It carries onychomycosis—Disease, deformity or Impetigo—A highly contagious bacterial a high mortality rate if untreated. While wasting of the nails caused by fungal skin infection caused by streptococcus or it is best known as a cause of meningitis, infection. staphylococcus. It mostly affects infants it also causes widespread blood infection and children and usually appears as red (sepsis), which is more damaging and Orphan Drug—A drug to treat a sores on the face, especially around the dangerous. Meningitis and meningococ- disease that has a patient population nose and mouth. cal sepsis are major causes of illness, of 200,000 or less, or a disease that death, and disability in both developed has a patient population of more than infl uenza—A viral infection of the respi- and underdeveloped countries worldwide. 200,000 and a development cost that ratory tract that causes fever, headache, will not be recovered from sales in the muscle ache and weakness.There are methicillin-resistant Staphylococcus United States. Orphan Drug status is three main types of infl uenza virus—A, B aureus (MRSA)—A type of bacteria that assigned by the U.S. Food and Drug and C. A person who has had an attack is resistant to certain antibiotics, includ- Administration. with the type C virus acquires antibod- ing methicillin and other more common ies that provide immunity against that antibiotics such as oxacillin, penicillin otitis externa—Also called “swimmer’s type for life. Anyone who has been and amoxicillin. Staph infections, including ear,” which is an infection of the skin infected with a certain strain of the type MRSA, occur most frequently among pa- covering the outer ear canal that leads in A or B viruses acquires immunity to that tients in hospitals and healthcare settings. to the ear drum, usually due to bacteria. strain. Both the A- and B-type viruses occasionally alter to produce new strains mycoses—Diseases caused by fungi. otitis media—Infl ammation of the that may be able to overcome immu- middle ear, often caused by a pneumo- nity. Type B is fairly stable, but type A Necrotizing soft tissue infections—A coccal infection. is highly unstable, and new strains of it rare but very severe type of bacterial

Medicines in Development Infectious Diseases 2013 43 Glossary

pediculosis—Infestation with lice, pneumococcal infections—Caused by rhinovirus—A genus of viruses that which are ectoparasites that live on the Streptococcus pneumoniae, or pneu- infect the upper respiratory tract and body. The three types of lice that infest mococcus, a gram-positive human cause the common cold. humans are: Pediculus humanus capitis pathogenic bacterium. The organism (head louse), Pediculus humanus corpo- causes many types of pneumococcal rotavirus—A group of viruses that are ris (body louse), and Pthirus pubis (pubic infections, including pneumonia, otitis wheel-like in appearance and are a major louse). The lice are spread from person media, meningitis, sepsis, endocarditis, source of infant diarrhea throughout the to person by close physical contact or and brain abscess. S. pneumoniae is world. through objects such as combs and the most common cause of bacterial sepsis—The presence of bacteria and/or clothes. The body louse is the vector of meningitis in adults and children and their toxins in the blood or tissues. typhus, trench fever, and relapsing fever. one of the top two isolates found in ear infection (otitis media). Pneumococcal Staphylococcus aureus—A common pertussis—Also called “whooping pneumonia is more common in the very bacterium that is a frequent cause of cough,” a communicable, potentially young and the very old. hospital infections, including pneumonia, deadly bacterial illness characterized by surgical wounds, and systemic blood fi ts of coughing followed by a noisy, pseudomonal infections—Infections infections. “whooping” indrawn breath. The illness due to Pseudomonas aeruginosa, a is most likely to affect young children, Gram-negative bacterium common in streptococcal infections—There are two but sometimes appears in teenagers soil and water. Pseudomonas aeruginosa types of “strep” infections—group A and and adults, even those who have been is an opportunistic pathogen, mean- group B—both of which are treated by previously immunized. Immunization with ing that it exploits some break in the antibiotics. Group A strep causes strep DPT (diphtheria-pertussis-tetanus) vac- host’s defenses to initiate an infection. throat, scarlet fever, impetigo, toxic cine provides protection, although that It causes urinary tract infections, respira- shock syndrome, cellulites, and necrotiz- immunity may wear off with age. When tory system infections, dermatitis, soft ing fasciitis (fl esh-eating disease). Group teenagers and adults get pertussis, it tissue infections, bacteremia, bone and B can cause blood infections, pneumo- appears fi rst as coughing spasms, and joint infections, gastrointestinal infec- nia, and meningitis in newborns. Adults then a stubborn dry cough lasting up to tions and a variety of systemic infections, can also get group B strep infections, eight weeks. particularly in patients with severe burns especially if they are elderly or already and in cancer and AIDS patients who are have health problems. Strep B can cause Phase 0—First-in-human trials conduct- immunosuppressed. urinary tract infections, blood infections, ed in accordance with FDA’s 2006 guid- skin infections, and pneumonia in adults. ance on exploratory Investigational New Rabies—A viral disease most often Drug (IND) studies designed to speed transmitted through the bite of a rabid tetanus—Also known as lockjaw, tetanus up development of promising drugs by animal. The vast majority of rabies cases is a serious but preventable disease that establishing very early on whether the reported to the Centers for Disease Con- affects the body’s muscles and nerves. agent behaves in human subjects as was trol and Prevention (CDC) each year oc- It typically arises from a skin wound that anticipated from preclinical studies. cur in wild animals like raccoons, skunks, becomes contaminated by a bacterium, bats, and foxes. The rabies virus infects which is often found in soil. Once the Phase I—Safety testing and pharmaco- the central nervous system leading to bacteria are in the body, they produce logical profi ling in humans. disease in the brain and death. a neurotoxin (a protein that acts as a poison to the body’s nervous system) Phase II—Effectiveness testing and iden- respiratory syncytial virus (RSV)—One tifi cation of side effects in humans. that causes muscle spasms. The toxin of the most important causes of lower can travel throughout the body via the respiratory tract disease in children. In Phase III—Extensive clinical trials in hu- bloodstream and lymph system. As it severe cases, cyanosis (bluish discolor- mans to verify effectiveness and monitor circulates more widely, the toxin inter- ation of skin and mucous membranes adverse reactions. feres with the normal activity of nerves due to defi cient oxygenation of the throughout the body, leading to general- blood) can result.

44 Medicines in Development Infectious Diseases 2013 Glossary

ized muscle spasms. Without treatment, tuberculosis—An infectious disease vaginosis, bacterial—An overgrowth tetanus can be fatal. Tetanus is rare in caused by the organism Mycobacterium of the bacteria Gardnerella and others, the United States and other nations with tuberculosis, which is passed from per- often associated with increased malodor- tetanus vaccination programs; however, son to person by breathing in airborne ous discharge without obvious vulvitis or the disease is much more common in droplets (from coughing or sneezing). vaginitis (infl ammation and infection of many developing countries. The bacteria multiply in the lungs and the vulva and vagina). in some cases can spread to the lymph tinea corporis—Also called “ringworm”, nodes. A person’s immune system most Yersinia—Three Gram-negative ba- a skin infection caused by a fungus. frequently will attack and heal the infec- cilli Yersinia species cause infection in tion, causing a scar on the lung. humans: Y. enterocolitica causes gastro- tinea curis—A fungal infection in the enteritis; Y. pseudotuberculosis causes groin area. Typhoid fever—A bacterial disease mesenteric lymphadenitis; and Y. pestis commonly transmitted by the ingestion causes plague. tinea pedis—Also called “athlete’s foot,” of food or water contaminated with the a skin infection caused by a fungus. feces from a person infected with the bacterium Salmonella typhi.

Medicines in Development Infectious Diseases 2013 45 The Drug Discovery, Development and Approval Process

Developing a new medicine takes an average of 10-15 years; For every 5,000-10,000 compounds in the pipeline, only 1 is approved. Drug Discovery and Development: A LONG, RISKY ROAD

DRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG Y

5,000–10,000 250 5 VEILLANCE ONE FDA-

VER COMPOUNDS APPROVED O DRUG

PHASE PHASE PHASE ARKETING SUR 1 2 3 -M ST NUMBER OF VOLUNTEERS PRE-DISC 20–80 100–300 1,000–3,000 A SUBMITTED 0.5–2 IND SUBMITTE D 3–6 YEARS6–7 YEARS ND

YEARS PHASE 4: PO The Drug Development and Approval Process The U.S. system of new drug approvals is in people. The IND shows results of previous ate statistically signifi cant evidence to confi rm perhaps the most rigorous in the world. experiments; how, where and by whom the new its safety and effectiveness. They are the lon- studies will be conducted; the chemical structure gest studies, and usually take place in multiple It takes 10-15 years, on average, for an experi- of the compound; how it is thought to work in sites around the world. mental drug to travel from lab to U.S. patients, the body; any toxic effects found in the animal according to the Tufts Center for the Study of New Drug Application (NDA)/Biologic License studies; and how the compound is manufac- Drug Development. Only fi ve in 5,000 com- Application (BLA). Following the completion tured. All clinical trials must be reviewed and ap- pounds that enter preclinical testing make it to of all three phases of clinical trials, a company proved by the Institutional Review Board (IRB) human testing. And only one of those fi ve is analyzes all of the data and fi les an NDA or BLA where the trials will be conducted. Progress approved for sale. with FDA if the data successfully demonstrate reports on clinical trials must be submitted at both safety and effectiveness. The applications On average, it costs a company $1.2 billion, least annually to FDA and the IRB. contain all of the scientifi c information that the including the cost of failures, to get one new Clinical Trials, Phase I—Researchers test the company has gathered. Applications typically medicine from the laboratory to U.S. patients, drug in a small group of people, usually between run 100,000 pages or more. according to a recent study by the Tufts Center 20 and 80 healthy adult volunteers, to evaluate for the Study of Drug Development. Approval. Once FDA approves an NDA or BLA, its initial safety and tolerability profi le, deter- the new medicine becomes available for physi- Once a new compound has been identifi ed in mine a safe dosage range, and identify potential cians to prescribe. A company must continue the laboratory, medicines are usually developed side effects. to submit periodic reports to FDA, including as follows: Clinical Trials, Phase II—The drug is given any cases of adverse reactions and appropriate Preclinical Testing. A pharmaceutical company to volunteer patients, usually between 100 and quality-control records. For some medicines, conducts laboratory and animal studies to show 300, to see if it is effective, identify an optimal FDA requires additional trials (Phase IV) to biological activity of the compound against the dose, and to further evaluate its short-term evaluate long-term effects. targeted disease, and the compound is evalu- safety. Discovering and developing safe and effective ated for safety. Clinical Trials, Phase III—The drug is given to a new medicines is a long, diffi cult, and expensive Investigational New Drug Application (IND). larger, more diverse patient population, often process. PhRMA member companies invested an After completing preclinical testing, a com- involving between 1,000 and 3,000 patients estimated $48.5 billion in research and develop- pany fi les an IND with the U.S. Food and Drug (but sometime many more thousands), to gener- ment in 2012. Administration (FDA) to begin to test the drug