2012 Repo r t

Medicines in Development presented by america’s biopharmaceutical research companies

Nearly 300 Vaccines Are in Development; Research Focuses on Prevention and Treatment

Vaccines in Development*

170

For many years, vaccines have been used Today, biopharmaceutical research companies to successfully prevent diseases such as are developing 295 vaccines. Potential vac- smallpox, measles, polio and other infectious cines in development include: diseases. A 2007 study by the U.S. Centers for • A recombinant against malaria. 102 Disease Control and Prevention (CDC) found that cases of vaccine-preventable diseases • A vaccine that protects infants against had reached an all-time low in the United meningococcal disease, a leading cause of meningitis. States. The study found that hospitalizations and deaths from nine infectious diseases had • A genetically-modified vaccine designed declined by more than 90 percent and nearly for the treatment of pancreatic cancer. 90 percent for another four diseases. Although many new promising vaccines are being researched today, the vaccine devel- These findings illustrate the major contribution opment process is not an easy one. As with that vaccines have made in saving countless the development of all drugs, vaccines must lives around the world. In the past several survive many years of thorough testing before years, many successful new vaccines have they can be approved for use by the general been developed, including one against human 12 public. Advances in other scientific fields, 8 papillomavirus (HPV) that can lead 7 such as genomics, are becoming increasingly to cervical cancer, one to guard against pre- useful in the development of new vaccines. y r s exposure to the virus, and a vaccine to With the continued efforts of researchers, it is Other Allerg prevent pneumococcal infections in high-risk Cance likely that we may have many more vaccines populations. to protect against life-threatening diseases in

Infectious Diseases Neurologic Disorder But vaccines are not only for preventing infec- the near future. tious diseases. In 2010, a new * Some vaccines are listed in for the treatment of prostate cancer was more than one category. approved in the United States, and many more are in development. Medicines in Development for Vaccines

Allergy

Product Name Sponsor Indication Development Status*

cat allergy vaccine Greer Laboratories perennnial allergic rhinitis due to Phase I sublingual Lenoir, NC cat hair (800) 419-7302

food allergy epicutaneous DBV Technologies peanut hypersensitivity Phase I immunotherapy Bagneux, France (Fast Track) www.dbv-technologies.com

grass pollen allergy ALK Abello seasonal allergic rhinitis Phase III vaccine tablet Horsholm, Denmark (800) 672-6372 (immunotherapy) Merck Whitehouse Station, NJ

grass pollen extract Stallergenes seasonal allergic rhinitis Phase III sublingual vaccine Norwell, MA (781) 878-0018

house dust mite allergy Greer Laboratories allergic rhinitis Phase I sublingual vaccine Lenoir, NC (800) 419-7302

house dust mite allergy ALK Abello allergic asthma Phase II vaccine tablet Horsholm, Denmark (800) 672-6372 Merck Whitehouse Station, NJ

peanut allergy vaccine Allertein Therapeutics peanut hypersensitivity Phase I Fairfield, CT

Pollinex® Quattro Allergy Therapeutics prevention of grass pollen Phase III injectable MPL allergy vaccine West Sussex, United Kingdom hypersensitivity, prevention of www.allergytherapeutics.com ragweed hypersensitivity ------prevention of tree pollen Phase II hypersensitivity www.allergytherapeutics.com

QGE031 Novartis Pharmaceuticals allergic diseases Phase I (anti-IgE ) East Hanover, NJ (888) 669-6682

ragweed allergy immunotherapy Stallergenes seasonal allergic rhinitis Phase I vaccine Norwell, MA (781) 878-0018

ragweed allergy vaccine Greer Laboratories seasonal allergic rhinitis Phase III sublingual Lenoir, NC (800) 419-7302

ragweed allergy vaccine ALK Abello seasonal allergic rhinitis Phase III sublingual tablet Horsholm, Denmark (800) 672-6372 Merck Whitehouse Station, NJ

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

2 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

abagovomab Menarini ovarian cancer Phase III (anti-idiotype mAb vaccine) Florence, Italy www.menarini.com

ADXS-HPV Advaxis recurrent cervical cancer, cervical Phase II (live, attenuated Listeria Princeton, NJ intraepithelial neoplasia (609) 452-9813 monocytogenes [Lm]-based vaccine)

AE37 Express breast cancer Phase II () Worcester, MA (508) 852-8783 ------ovarian cancer (combination Phase I therapy), prostate cancer (508) 852-8783

AGS-003 Argos Therapeutics kidney cancer (combination therapy), Phase II (personalized dendritic Durham, NC metastatic kidney cancer (919) 287-6300 cell-based immunotherapy) (monotherapy)

AlloStim™ Novo Energies hematological malignancies, Phase I/II immunotherapeutic vaccine Montreal, Canada solid tumors (514) 840-3697

anti-GnRH vaccine Novartis Vaccines & Diagnostics prostate cancer Phase I/II Cambridge, MA (617) 871-7000 Pepscan Therapeutics Lelystad, Netherlands

astuprotimut-R GlaxoSmithKline malignant melanoma, non-small-cell Phase III (MAGE-A3 recombinant Rsch. Triangle Park, NC lung cancer (NSCLC) (888) 825-5249 antigen-specific cancer ------immunotherapy) bladder cancer Phase II (888) 825-5249

AVX-701 AlphaVax prevention of advanced or metastatic Phase I/II Rsch. Triangle Park, NC CEA-expressing colorectal cancer (919) 595-0400

B7-2/GM-CSF NuVax Therapeutics cancer Phase I cancer gene therapy vaccine Tustin, CA (714) 505-4461

BiovaxID® International indolent follicular lymphoma Phase III B-cell lymphoma vaccine Tampa, FL (Fast Track) (813) 864-2558 (personalized lymphoma ------vaccine) mantle-cell lymphoma Phase II (813) 864-2558

BPX-101 Bellicum Pharmaceuticals prostate cancer Phase I/II (dendritic cell vaccine) Houston, TX www.bellicum.com

breast cancer vaccine Quantum Immunologics breast cancer Phase I/II (dendritic cell vaccine) Tampa, FL (813) 849-7885

Medicines in Development Vaccines 2012 3 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

cancer vaccine Immunovaccine ovarian cancer Phase I Halifax, Canada (902) 492-1819

cancer vaccine Activartis Biotech glioblastoma (first-line therapy) Phase II (autologous dendritic cell Vienna, Austria www.activartis.com vaccine) ------metastatic renal cancer in clinical trials www.activartis.com

cancer vaccine Bayer HealthCare Pharmaceuticals follicular lymphoma (prevention of Phase I (autologous idiotype vaccine) Wayne, NJ relapse) (888) 842-2937

cancer vaccine Cytokine PharmaSciences cancer Phase I (fibrocyte vaccine) King of Prussia, PA (610) 687-1776

cancer vaccine MabVax Therapeutics sarcoma Phase II (mAb vaccine) San Diego, CA (858) 259-9405 ------breast cancer Phase I (858) 259-9405

CB-10-01 Cosmo Pharmaceuticals malignant melanoma Phase II Lainate, Italy www.cosmopharmaceuticals. com

CDX-1401 Celldex Therapeutics solid tumors expressing the Phase I/II Needham, MA NY-ESO-1 protein (781) 433-0771

CG201 CG Therapeutics solid tumors Phase II Seattle, WA (206) 336-5604

CLL MaxCyte chronic lymphocytic leukemia (CLL) Phase I/II immunotherapeutic Gaithersburg, MD (301) 944-1700

CRS-207 Aduro BioTech metastatic pancreatic cancer Phase II Berkeley, CA (combination therapy) (510) 848-4400

CV-301 BN ImmunoTherapeutics metastatic breast cancer Phase II (immunotherapeutic vaccine) () (650) 681-4660 Mountain View, CA

CVac™ Prima Biomed ovarian cancer Phase II/III cancer vaccine Sydney, Australia www.primabiomed.com.au MUC-1

4 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

DCVax®-Brain Northwest Biotherapeutics glioblastoma Phase II dendritic cell-based vaccine Bethesda, MD (240) 497-9024 (Orphan Drug)

DCVax®-Ovarian Northwest Biotherapeutics ovarian cancer, peritoneal cancer Phase I dendritic cell-based vaccine Bethesda, MD (240) 497-9024

DCVax®-Prostate Northwest BioTherapeutics prostate cancer Phase III dendritic cell-based vaccine Bethesda, MD (240) 497-9024

dendritic cell cancer vaccine EMD Serono malignant melanoma Phase I Rockland, MA (800) 283-8088

DN24-02 Dendreon HER2-positive urogenital cancer Phase II (lapuleucel-T) Seattle, WA (adjuvant therapy) (877) 256-4545 (dendritic cell vaccine) ------breast cancer, colorectal cancer, Phase I completed ovarian cancer (877) 256-445

DPX-0907 Immunovaccine breast cancer, ovarian cancer, Phase I Halifax, Canada prostate cancer (902) 492-1819

EC17 Endocyte kidney cancer Phase I West Lafayette, IN (combination therapy) www.endocyte.com

ETBX-011 Etubics solid tumors Phase I (adenovirus vector vaccine) Seattle, WA (206) 838-5110

FANG™ vaccine Gradalis malignant melanoma, ovarian cancer Phase II (autologous tumor cell vaccine) Carrollton, TX (214) 442-8100

FBP vaccine endometrial cancer, ovarian cancer Phase I/II (folate-binding protein Lake Oswego, OR (855) 855-4253 E39 vaccine) ------breast cancer Phase I (855) 855-4253

G-100 prophage cancer vaccine Agenus newly-diagnosed glioma Phase II (Orphan Drug) Lexington, MA (781) 674-4400

G-200 prophage cancer vaccine Agenus recurrent glioma Phase II (Orphan Drug) Lexington, MA (781) 674-4400

Medicines in Development Vaccines 2012 5 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

GI-4000 GlobeImmune colorectal cancer, pancreatic cancer Phase II (therapeutic vaccine) Louisville, CO (303) 625-2700 ------colorectal cancer (first-line therapy), Phase I colorectal cancer (second-line (303) 625-2700 therapy), NSCLC

GI-6207 GlobeImmune metastatic cancer Phase I (therapeutic vaccine) Louisville, CO (303) 625-2700

GI-6301 GlobeImmune solid tumors Phase I (brachyury peptide vaccine) Louisville, CO (303) 625-2700

GRNVAC1 Geron acute myeloid leukemia (AML) Phase II (telomerase-based cancer Menlo Park, CA (650) 473-7700 vaccine) ------prostate cancer Phase I/II (650) 473-7700

GSK2241658A GlaxoSmithKline metastatic melanoma Phase I (NY-ESO-1 antigen-specific Rsch. Triangle Park, NC (888) 825-5249 cancer immunotherapeutic)

GV1001 KAEL-GemVax pancreatic cancer Phase I (hTERT RNA vaccine) Seoul, www.kaelgemvax.com (Orphan Drug)

GVAX® Breast BioSante Pharmaceuticals breast cancer Phase I immunotherapeutic vaccine Lincolnshire, IL (847) 478-0500

GVAX® Colorectal BioSante Pharmaceuticals colorectal cancer Phase I immunotherapeutic vaccine Lincolnshire, IL (847) 478-0500

GVAX® Leukemia BioSante Pharmaceuticals AML, chronic myeloid leukemia Phase II immunotherapeutic vaccine Lincolnshire, IL (CML) (847) 478-0500 (Orphan Drug)

GVAX® Myeloma BioSante Pharmaceuticals multiple myeloma Phase II immunotherapeutic vaccine Lincolnshire, IL (847) 478-0500

GVAX® Pancreatic BioSante Pharmaceuticals pancreatic cancer Phase II immunotherapeutic vaccine Lincolnshire, IL (847) 478-0500 (Orphan Drug)

GVAX® Prostate BioSante Pharmaceuticals prostate cancer Phase III immunotherapeutic vaccine Lincolnshire, IL (Fast Track) (847) 478-0500

6 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

HS-110 Heat Biologics NSCLC (combination therapy) Phase II Chapel Hill, NC (919) 240-7133

hTERT vaccine Merck cancer Phase I (human telomerase reverse Whitehouse Station, NJ (800) 672-6372 transcriptase cancer vaccine) Vical (858) 646-1100 San Diego, CA

HyperAcute® Lung NewLink Genetics NSCLC Phase II lung Ames, IA (515) 296-5555

HyperAcute® Melanoma NewLink Genetics malignant melanoma Phase II lung cancer immunotherapy Ames, IA (515) 296-5555

HyperAcute® Pancreas NewLink Genetics pancreatic cancer Phase III algenpantucel-L Ames, IA (Fast Track) (515) 296-5555 (Orphan Drug)

ICT-107 ImmunoCellular Therapeutics glioblastoma Phase II (autologous dendritic-cell Woodland Hills, CA (818) 992-2907 vaccine) (Orphan Drug)

IDM-2101 Biotech Synergy NSCLC Phase II (multi-epitope cancer vaccine) San Diego, CA (858) 459-6689

IMA901 immatics biotechnologies kidney cancer Phase III (multiple tumor-associated Tuebingen, Germany www.immatics.com peptides cancer vaccine)

IMCgp100 Immunocore malignant melanoma Phase 0 Oxon, United Kingdom www.immunocore.com

IMF-001 ImmunoFrontier solid tumors Phase I (protein vaccine) Tokyo, Japan www.immunofrontier.com

IMT-1012 Immunotope breast cancer, ovarian cancer Phase I (multi-peptide antigen Doylestown, PA (215) 253-4180 immunotherapeutics vaccine)

ISF35 Memgen CLL (monotherapy), Phase II (recombinant immunotherapy) San Diego, CA non-Hodgkin’s lymphoma (858) 524-5400 ------CLL (combination therapy) Phase I (858) 524-5400

Medicines in Development Vaccines 2012 7 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

JVRS-100 Colby Pharmaceutical leukemia Phase I (lipid-DNA complex vaccine) San Jose, CA (650) 333-3152

Lucanix® NovaRx NSCLC Phase III belagenpumatucel-L San Diego, CA (Fast Track) (858) 552-8600 (cell-based therapeutic vaccine) ------glioma Phase I (858) 552-8600

LungVax® NSCLC Phase I/II autologous cell vaccine Philadelphia, PA (215) 241-9760

M-200 prophage cancer vaccine Agenus metastatic melanoma Phase III (Orphan Drug) Lexington, MA (Fast Track) (781) 674-4400

melanoma DNA vaccine Ichor Medical Systems malignant melanoma Phase I San Diego, CA (858) 550-2022 Memorial Sloan-Kettering Cancer Center New York, NY

MVA-BN® Breast BN ImmunoTherapeutics breast cancer Phase I HER-2/neu-based modified (Bavarian Nordic) (650) 681-4660 ankara (MVA) vaccine Mountain View, CA

MVA-BN®-PRO BN ImmunoTherapeutics prostate cancer Phase I/II (Bavarian Nordic) (650) 681-4660 Mountain View, CA

MVax® AVAX Technologies malignant melanoma Phase III autologous cell vaccine Philadelphia, PA (215) 241-9760

NeuVax™ Galena Biopharma early-stage breast cancer Phase III E75 cancer vaccine Lake Oswego, OR (prevention of relapse) (855) 855-4253 ------prostate cancer Phase I/II (855) 855-4253

Oncophage® Agenus renal cell carcinoma Phase II vitespen Lexington, MA (Fast Track) (781) 674-4400 (Orphan Drug)

OncoVAX® Vaccinogen stage III colorectal cancer Phase II colorectal cancer vaccine Frederick, MD (combination therapy) (301) 668-8400 ------colorectal cancer Phase I/II (Fast Track) (301) 668-8400

ONT-10 Oncothyreon solid tumors Phase I Seattle, WA (206) 801-2100

8 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

OPT-822 Optimer Pharmaceuticals breast cancer Phase II San Diego, CA (858) 909-0736

oral peptide cancer vaccine Immunitor cancer Phase I/II Vancouver, Canada

oregovomab Quest PharmaTech ovarian cancer Phase I/II (Orphan Drug) Edmonton, Canada (780) 448-1400

OVax® AVAX Technologies ovarian cancer Phase I/II autologous tumor cell vaccine Philadelphia, PA (215) 241-9760 (Orphan Drug)

POL-103A Polynoma malignant melanoma Phase II (polyvalent shed-antigen San Diego, CA (858) 205-2501 vaccine) (Orphan Drug)

polyclonal antibody stimulator Cancer Advances gastric cancer, pancreatic cancer Phase III (Orphan Drug) Durham. NC (see also other) (919) 361-2162 ------colorectal cancer Phase II (919) 361-2162

PRAME GlaxoSmithKline metastatic melanoma, NSCLC Phase I antigen-specific cancer Rsch. Triangle Park, NC (888) 825-5249 immunotherapeutic

Prostvac™ BN ImmunoTherapeutics metastatic prostate cancer Phase III prostate cancer vaccine (Bavarian Nordic) (Fast Track) (650) 681-4660 Mountain View, CA

Provenge® Dendreon recurrent early-stage prostate cancer Phase III sipuleucel-T Seattle, WA (877) 256-4545 ------early-stage prostate cancer Phase II (neoadjuvant therapy) (877) 256-4545

PSMA VRP therapeutic vaccine Progenics Pharmaceuticals prostate cancer Phase I Tarrytown, NY (914) 789-2800

PT107 Pique Therapeutics NSCLC Phase II (allogeneic tumor cell vaccine) Durham, NC (919) 806-4395

recombinant soluble PSMA Progenics Pharmaceuticals prostate cancer Phase I protein vaccine Tarrytown, NY (914) 789-2800

Medicines in Development Vaccines 2012 9 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

REIC gene therapy Momotaro-Gene prostate cancer Phase I Okayama, Japan www.mt-gene.com

Reximmune-C® Epeius Biotechnologies breast cancer Phase I/II personalized cancer vaccine San Marino, CA (626) 441-6695

rindopepimut Celldex Therapeutics glioblastoma (first-line therapy) Phase III (Orphan Drug) Needham, MA (Fast Track) (781) 433-0771 ------glioblastoma (combination therapy, Phase II second-line therapy) (781) 433-0771 (Fast Track)

SL-701 Stemline Therapeutics glioma Phase I/II (dendritic cell vaccine) New York, NY (212) 831-1111

Stimuvax® EMD Serono NSCLC (Fast Track) Phase III emepepimut-S Rockland, MA (800) 283-8088 Oncothyreon ------(206) 769-9219 Seattle, WA prostate cancer ------Phase II (800) 283-8088 (206) 769-9219

TAG vaccine Gradalis solid tumors Phase I Carrollton, TX (214) 442-8100

TeloB-Vax Adamis Pharmaceuticals prostate cancer Phase I telomerase cancer vaccine San Diego, CA www.adamispharma.com

tipapkinogene sovacivec Transgene cervical intraepithelial neoplasia Phase II Rockville, MD (301) 816-5421

TroVax® Oxford BioMedica hormone refractory prostate cancer Phase II tumor-associated antigen Oxford, United Kingdom www.oxfordbiomedica.co.uk vaccine

TVI-Brain-1 TVAX Biomedical glioma Phase II (cellular immunotherapy Lenexa, KS (913) 492-2221 vaccine)

TVI-Kidney-1 TVAX Biomedical renal cell carcinoma in clinical trials (cellular immunotherapy Lenexa, KS (913) 492-2221 vaccine)

V503 Merck prevention of cervical cancer, Phase III (virus-like particle [VLP] Whitehouse Station, NJ prevention of vulvovaginal cancer (800) 672-6372 vaccine) (see also infectious diseases)

10 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Cancer

Product Name Sponsor Indication Development Status

V505 Merck prevention of cervical cancer Phase II completed Whitehouse Station, NJ (see also infectious diseases) (800) 672-6372

V930/V932 Merck cancer Phase I (plasmid DNA cancer vaccine) Whitehouse Station, NJ (800) 672-6372 Vical (858) 646-1100 San Diego, CA

V935 Geron solid tumors Phase I (telomerase inhibitor vaccine) Menlo Park, CA (650) 473-7700 Merck (800) 672-6372 Whitehouse Station, NJ

verpasep caltespen Akela Pharma cervical intraepithelial neoplasia Phase I completed Austin, TX (512) 834-0449

VGX-3100 Inovio Pharmaceuticals cervical intraepithelial neoplasia Phase II Blue Bell, PA (see also infectious diseases) (877) 446-6846

WT1 antigen specific cancer GlaxoSmithKline AML Phase II immunotherapeutic Rsch. Triangle Park, NC (888) 825-5249 ------breast cancer Phase I (888) 825-5249

Infectious Diseases

Product Name Sponsor Indication Development Status

ACAM-Cdiff sanofi pasteur Clostridium difficile infections Phase II ( vaccine) Swiftwater, PA (800) 822-2463

ACE527 ACE Biosciences prevention of traveler’s diarrhea Phase II (oral ) Odense, Denmark caused by Escherichia coli infections www.acebiosciences.com TD Vaccines www.tdvaccines.com Skorping, Denmark

Ad26.ENVA.01 Crucell prevention of HIV Phase I HIV-1 recombinant vaccine Leiden, Netherlands www.crucell.com

ADVAX Aaron Diamond AIDS Research HIV infection prevention Phase I completed (DNA vaccine) Center (212) 448-5000 New York, NY (212) 847-1111 International AIDS Vaccine Initiative ------New York, NY HIV infection prevention Phase I completed Ichor Medical Systems (new delivery system) (212) 448-5000 San Diego, CA (212) 847-1111

Medicines in Development Vaccines 2012 11 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

Aflunov™ Novartis Vaccines & Diagnostics prevention of influenza A virus H5N1 Phase II influenza A virus Cambridge, MA subtype (pre-pandemic) (617) 871-7000

AG-707 Agenus treatment of herpes simplex virus Phase I completed (herpes simplex vaccine) Lexington, MA infections (781) 674-4400

AGS-004 Argos Therapeutics HIV-1 infection Phase II (personalized dendritic Durham, NC (919) 287-6300 cell-based immunotherapy)

anthrax transdermal vaccine Intercell USA anthrax Phase I Gaithersburg, MD (301) 556-4500

ANZ-521 Aduro BioTech treatment of hepatitis C Phase I (recombinant vaccine) Berkeley, CA (510) 848-4400

AV-7909 Emergent BioSolutions anthrax Phase I ( with Rockville, MD (301) 795-1800 adjuvant)

AVX-101 AlphaVax prevention of HIV-1 infection Phase I completed (monovalent HIV vaccine) Rsch. Triangle Park, NC (919) 595-0400

AVX-502 AlphaVax prevention of influenza virus Phase I/II Rsch. Triangle Park, NC infections in the elderly (919) 595-0400

BioThrax® Emergent BioSolutions anthrax (post-exposure prevention) Phase III anthrax vaccine adsorbed Rockville, MD (Fast Track) (301) 795-1800

botulinum toxin recombinant DynPort Vaccine Company botulism Phase II vaccine Frederick, MD (301) 607-5000

virus vaccine Inviragen chikungunya virus infections Phase II Fort Collins, CO (970) 672-4918

CholeraGarde® Vaccine Technologies cholera Phase II live attenuated Boston, MA (617) 358-5011

ChronVac-C® Inovio Pharmaceuticals treatment of hepatitis C Phase II hepatitis C DNA vaccine Blue Bell, PA (877) 446-6846 ChronTech Pharma Huddinge, Sweden

AlphaVax prevention of cytomegalovirus Phase I (AVX-601) Rsch. Triangle Park, NC infections (617) 871-7000 Novartis Vaccines & Diagnostics Cambridge, MA

12 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

DCVax-001 Celldex Therapeutics prevention and treatment of HIV Phase I (recombinant protein vaccine) Needham, MA infection (781) 433-0771

dengue DNA vaccine U.S. Naval Medical Research Center prevention of dengue fever Phase I Silver Spring, MD (858) 646-1100 Vical San Diego, CA

dengue fever vaccine GlaxoSmithKline prevention of dengue fever Phase II completed Rsch. Triangle Park, NC (888) 825-5249

dengue fever vaccine sanofi pasteur prevention of mild to severe dengue Phase III Swiftwater, PA fever (800) 822-2463 (Fast Track)

DENVax™ Inviragen dengue Phase I tetravalent hybrid dengue virus Fort Collins, CO (970) 672-4918 vaccine

DermaVir™ Patch Genetic treatment of HIV-1 infection Phase II DNA topical patch vaccine McLean, VA (703) 879-6803

DTP-HepB-Polio-Hib Merck diphtheria, tetanus, pertussis, Phase III Whitehouse Station, NJ hepatitis B, poliomyelitis, (800) 672-6372 sanofi pasteur Haemophilus influenzae type b (800) 822-2463 Swiftwater, PA (infants)

DV-601 Dynavax treatment of hepatitis B Phase I (therapeutic vaccine) Berkeley, CA (510) 848-5100

Ebola vaccine Crucell prevention of Ebola virus infections Phase I Leiden, Netherlands www.crucell.com Vaccine Research Center (NIAID) Bethesda, MD

Ebola virus vaccine GenPhar Ebola virus infections in clinical trials Mt. Pleasant, SC (843) 884-0120

EP1043 VaxOnco prevention of HIV-1 infections Phase I (recombinant protein vaccine) Seoul, South Korea www.vaxonco.com National Institute of Allergy and Infectious Diseases Bethesda, MD

EP1090 VaxOnco prevention and treatment of HIV-1 Phase I/II (DNA vaccine) Seoul, South Korea infections www.vaxonco.com National Institute of Allergy and Infectious Diseases Bethesda, MD

Medicines in Development Vaccines 2012 13 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

EP1300 VaxOnco prevention of malaria Phase I (DNA vaccine) Seoul, South Korea www.vaxonco.com National Institutes of Health Bethesda, MD

ETEC vaccine Vaccine Technologies prevention of cholera, Escherichia Phase I Boston, MA coli infections (617) 358-5011

FluBlok® Protein Sciences prevention of influenza virus application submitted influenza virus vaccine Meridian, CT infections (adults and children) (800) 488-7099 (Fast Track)

FluLaval™ GlaxoSmithKline prevention of influenza virus Phase III completed influenza virus vaccine Rsch. Triangle Park, NC infections (888) 825-5249 (pediatric)

Fluvirin® Novartis Vaccines & Diagnostics prevention of influenza A virus H1N1 Phase II/III completed influenza A virus H1N1 vaccine Cambridge, MA subtype (pediatric) (617) 871-7000

Fluzone® QIV IM sanofi pasteur influenza virus infections Phase III quadrivalent inactivated influ- Swiftwater, PA (800) 822-2463 enza vaccine

GelVac™ Nanotherapeutics influenza virus infections Phase I H5N1 influenza virus vaccine Alachua, FL (386) 462-9663 intranasal

GI-5005 GlobeImmune hepatitis C (combination therapy) Phase II (therapeutic vaccine) Louisville, CO (303) 625-2700

GSK1437173A GlaxoSmithKline prevention of varicella zoster virus Phase III (varicella ) Rsch. Triangle Park, NC infections (888) 825-5249

GSK1492903A GlaxoSmithKline prevention of cytomegalovirus Phase I (recombinant glycoprotein Rsch. Triangle Park, NC infections (888) 825-5249 vaccine)

GSK2189242A GlaxoSmithKline prevention of pneumococcal Phase II (Streptococcus pneumoniae Rsch. Triangle Park, NC infections (888) 825-5249 recombinant conjugated vaccine)

GSK2254232A GlaxoSmithKline prevention of Haemophilus Phase I completed (Haemophilus influenzae, Rsch. Triangle Park, NC infections, prevention of (888) 825-5249 pneumococcal recombinant pneumococcal infections vaccine)

14 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

GSK2254233A GlaxoSmithKline prevention of Haemophilus Phase I completed (Haemophilus influenzae, Rsch. Triangle Park, NC infections, prevention of (888) 825-5249 pneumococcal recombinant pneumococcal infections vaccine)

GSK2282512A GlaxoSmithKline prevention of influenza virus application submitted (influenza virus vaccine) Rsch. Triangle Park, NC infections (adults, adolescents and (888) 825-5249 children)

GSK2321138A GlaxoSmithKline prevention of influenza virus application submitted (influenza virus vaccine) Rsch. Triangle Park, NC infections (adults, adolescents and (888) 825-5249 children)

GSK2340273A GlaxoSmithKline prevention of influenza A virus Phase II (influenza A virus Rsch. Triangle Park, NC H1N1 subtype (children and infants) (888) 825-5249 H1N1 vaccine)

GSK2340274A GlaxoSmithKline prevention of influenza A virus H1N1 Phase II (influenza A virus vaccine) Rsch. Triangle Park, NC subtype (children and infants) (888) 825-5249 ------influenza A virus H5N1 subtype Phase I (888) 825-5249

GSK2392102A GlaxoSmithKline staphylococcal infections Phase I (Staphylococcus aureus Rsch. Triangle Park, NC (888) 825-5249 vaccine)

GSK2830930A GlaxoSmithKline pneumococcal infections Phase I () Rsch. Triangle Park, NC (888) 825-5249

H5N1 influenza virus vaccine Novavax prevention of influenza A virus H5N1 Phase II (recombinant) Rockville, MD subtype (240) 268-2000

H5N1 influenza virus vaccine Vaxart prevention of influenza A virus H5N1 Phase I San Francisco, CA subtype (415) 437-0132

H5N1 pandemic influenza virus GlaxoSmithKline prevention of influenza A virus H5N1 application submitted vaccine Rsch. Triangle Park, NC subtype (888) 825-5249 ------prevention of influenza A virus H5N1 Phase III subtype (children and adolescents) (888) 825-5249

HBV-002 Biotech prevention of West Nile virus Phase I completed (recombinant ) Aiea, HI infection (808) 486-5333

Helicobacter pylori vaccine Novartis Vaccines & Diagnostics helicobacter infections Phase I Cambridge, MA (617) 871-7000

Medicines in Development Vaccines 2012 15 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

hepatitis B DNA vaccine hepatitis B Phase I New York, NY (860) 732-5156

Emergent BioSolutions hepatitis B Phase II Rockville, MD (301) 795-1800

Okairos prevention of hepatitis C Phase I/II Rome, Italy www.okairos.il

hepatitis C vaccine Novartis Vaccines & Diagnostics treatment of hepatitis C Phase I/II (HCV/MF59) Cambridge, MA (617) 871-7000

Heplisav™ Dynavax prevention of hepatitis B Phase III hepatitis B vaccine 1018-ISS Berkeley, CA (510) 848-5100 conjugate

herpes simplex DNA vaccine Pfizer treatment of herpes simplex virus Phase I New York, NY infections (860) 732-5156

herpes simplex vaccine AuRx prevention and treatment of herpes Phase I/II Elkridge, MD (410) 796-759

Hexaxim® sanofi pasteur diptheria, tetanus, pertussis, application submitted DTP-HepB-Polio- Swiftwater, PA hepatitis B, poliomyelitis, (800) 822-2463 Haemophilus influenzae type b (infants)

HIVAX™ GeneCure Biotechnologies HIV-1 infection Phase I replication-defective HIV-1 Norcross, GA (770) 263-7508 vaccine

HIV recombinant vaccine GlaxoSmithKline treatment of HIV infection Phase II (gag/pol/nef) Rsch. Triangle Park, NC (888) 825-5249

HIV recombinant vaccine GlaxoSmithKline prevention of HIV-1 infection Phase I completed (gp120/NefTat/AS02A) Rsch. Triangle Park, NC (888) 825-5249

HIV vaccine GeoVax Labs prevention of HIV infection Phase II Smyrna, GA (678) 384-7220

HIV vaccine GeoVax Labs treatment of HIV infection Phase I/II Smyrna, GA (678) 384-7220

HIV vaccine Novartis Vaccines & Diagnostics HIV infection Phase I Cambridge, MA (617) 871-7000

16 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

HIV vaccine Opal Therapeutics HIV infection Phase I Palo Alto, CA (617) 726-2000 Massachusetts General Hospital Boston, MA

HIV vaccine Profectus Biosciences prevention of HIV infection Phase I (MAG pDNA) Baltimore, MD (866) 938-8559

HIV vaccine Profectus Biosciences prevention of HIV infection Phase I (rVSV) Baltimore, MD (866) 938-8559

Imvamune® BM ImmunoTherapeutics smallpox Phase II (Bavarian Nordic) (650) 681-4660 Mountain View, CA

influenza A virus H1N1 vaccine CEL-SCI prevention and treatment of influenza Phase I Vienna, VA A virus H1N1 subtype (703) 506-9460

influenza A virus H1N1 vaccine iBio prevention of influenza A virus H1N1 Phase I Newark, DE subtype www.ibioinc.com Fraunhofer USA Center for Molecular Biotechnology Newark, DE

influenza A virus H5N1 GlaxoSmithKline prevention of influenza A virus H5N1 Phase I cell culture-based vaccine Rsch. Triangle Park, NC subtype (pandemic use) (888) 825-5249

influenza A virus H5N1 vaccine Baxter Healthcare prevention of influenza A virus H5N1 Phase I Deerfield, IL subtype (800) 422-9837

influenza A virus vaccine H1N1 Medicago USA prevention of influenza A virus H1N1 Phase I Durham, NC subtype (919) 313-9670

influenza A virus vaccine H5N1 iBio prevention of influenza A virus H5N1 Phase I Newark, DE subtype www.ibioinc.com

influenza A virus vaccine H9N2 Baxter Healthcare prevention of influenza A virus H9N2 Phase I/II Deerfield, IL subtype (800) 422-9837

influenza virus DNA vaccine Vical prevention of influenza A virus H1N1 Phase I completed San Diego, CA subtype (858) 646-1100

influenza virus vaccine Dynavax prevention of influenza virus Phase I Berkeley, CA infections (510) 848-5100

influenza virus vaccine Novartis Vaccines & Diagnostics influenza virus infections Phase III (Fluad) Cambridge, MA (children and elderly) (617) 871-7000

Medicines in Development Vaccines 2012 17 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

influenza virus vaccine Vaxin influenza virus infections Phase I intranasal Birmingham, AL (205) 413-8238

Influvac® TC prevention of influenza virus Phase I cell culture-derived influenza Abbott Park, IL infections (847) 937-6100 vaccine

INO-3510 Inovio Pharmaceuticals influenza A virus H1N1 subtype, Phase I (DNA vaccine) Blue Bell, PA influenza A virus H5N1 subtype (877) 466-6846

Ixiaro® Intercell prevention of Japanese encephalitis Phase III Japanese encephalitis vaccine Vienna, Austria (pediatric) (617) 871-7000 Novartis Vaccines & Diagnostics Cambridge, MA

Ii-Key hybrid peptide vaccine Antigen Express influenza A virus H1N1 subtype Phase I Worcester, MA (508) 852-8783

LIQ-001 Liquidia Technologies influenza virus infections Phase I Rsch. Triangle Park, NC (919) 328-4400

Lyme disease vaccine Bayer HealthCare Pharmaceuticals prevention of Phase I/II Wayne, NJ (888) 842-2937

malaria DNA vaccine U.S. Naval Medical Research Center malaria Phase I/II Silver Spring, MD (858) 646-1100 Vical San Diego, CA

GenVec malaria Phase I/II Gaithersburg, MD (877) 943-6832 U.S. Naval Medical Research Center Silver Spring, MD

malaria vaccine Sanaria malaria Phase I/II Rockville, MD (301) 770-3222

malaria vaccine Crucell malaria Phase I (recombinant) Leiden, Netherlands www.crucell.com

malaria vaccine Crucell prevention of malaria Phase I/II (recombinant combination Leiden, Netherlands www.crucell.com vaccine) GlaxoSmithKline (888) 825-5249 Rsch. Triangle Park, NC

Marburg virus DNA vaccine GenPhar Marburg virus disease in clinical trials Mt. Pleasant, SC (843) 884-0120

MEDI-534 MedImmune prevention of parainfluenza and Phase I (RSV/PIV-3 vaccine) Gaithersburg, MD respiratory syncytial virus infections (301) 398-0000

18 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

MEDI-550 MedImmune prevention of pandemic influenza Phase I (pandemic influenza virus Gaithersburg, MD (H5N1 subtype) (301) 398-0000 vaccine)

MEDI-559 MedImmune prevention of respiratory syncytial Phase I (RSV vaccine) Gaithersburg, MD virus infections (pediatric) (301) 398-0000

MenABCWY Novartis Vaccine & Diagnostics prevention of meningococcal groups Phase II (multivalent ) Cambridge, MA A, B, C, Y and W-135 infections (617) 871-7000 (adolescents)

MenHibrix® GlaxoSmithKline prevention of Neisseria meningitidis application submitted Hib-MenCY-TT conjugated Rsch. Triangle Park, NC groups C and Y infections and (888) 825-5249 vaccine Haemophilus influenzae type B

Meninge ACYW sanofi pasteur meningococcal infections Phase II (second-generation Swiftwater, PA (800) 822-2463 meningococcal conjugate infant vaccine)

group B Novartis Vaccines & Diagnostics meningococcal group B infections Phase II quadrivalent recombinant Cambridge, MA (617) 871-7000 vaccine (4CMenB)

Menveo® Infants Novartis Vaccines & Diagnostics prevention of meningococcal A, C, Y application submitted meningococcal vaccine groups Cambridge, MA and W-135 infections (infants) (617) 871-7000 ACYW-135 conjugate vaccine

MMR vaccine GlaxoSmithKline prevention of measles, mumps and Phase II (live attenuated trivalent Rsch. Triangle Park, NC rubella (888) 825-5249 vaccine)

Mosquirix™ GlaxoSmithKline malaria Phase III malaria recombinant vaccine Rsch. Triangle Park, NC (888) 825-5249

MVA-BN® HIV BN ImmunoTherapeutics prevention and treatment of HIV-1 Phase I/II completed HIV multiantigen vaccine (Bavarian Nordic) infection (650) 681-4660 Mountain View, CA

MVA-BN® Polytope BN ImmunoTherapeutics prevention of HIV infection Phase I HIV vaccine (Bavarin Nordic) (650) 681-4660 Mountain View, CA

NB-1008 NanoBio prevention of influenza virus Phase I (intranasal vaccine) Ann Arbor, MI infections (734) 302-4000

Medicines in Development Vaccines 2012 19 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

NDV-3 NovaDigm Therapeutics prevention of candidiasis, prevention Phase I (recombinant protein vaccine) Grand Forks, ND of staphylococcal (MRSA) infections (701) 757-5161

Nimenrix™ GlaxoSmithKline prevention of meningococcal groups Phase III MenACWY-TT conjugated Rsch. Triangle Park, NC A, C, Y and W-135 infections (888) 825-5249 vaccine (children) ------prevention of meningococcal groups Phase II A, C, Y and W-135 infections (888) 825-5249 (adults, adolescents, infants)

NmVac JN-International Medical prevention of meningococcal groups Phase I (meningococcal vaccine groups Omaha, NE A, C, Y, and W-135 infections (402) 884-3477 ACWY conjugate vaccine)

norovirus bivalent vaccine LigoCyte Pharmaceuticals norovirus infections Phase I Bozeman, MT (406) 585-2733

norovirus monovalent vaccine LigoCyte Pharmaceuticals norovirus infections Phase I/II Bozeman, MT (406) 585-2733

Optaflu® Novartis Vaccines & Diagnostics prevention of influenza virus application submitted influenza virus vaccine Cambridge, MA infections (617) 871-7000

PanBlok™ Protein Sciences prevention of influenza A virus H5N1 Phase I/II influenza A virus H5N1 vaccine Meriden, CT subtype (pandemic) (800) 488-7099

parvovirus B19 vaccine Meridian Biosciences parvovirus infections Phase I/II Cincinnati, OH (513) 271-3700

PENNVAX™-B Inovio Pharmaceuticals prevention and treatment of HIV Phase I DNA vaccine (clade B) Blue Bell, PA infection (267) 440-4200

PENNVAX™-G Inovio Pharmaceuticals prevention of HIV infection Phase I DNA vaccine (clade A, C, D) Blue Bell, PA (267) 440-4200

PER.C-flu vaccine Crucell prevention of influenza virus Phase II Leiden, Netherlands infections www.crucell.com

PF-05212366 Pfizer adolescent meningitis Phase II (MnB rLP2086) New York, NY (860) 732-5156 ------infant meningitis Phase I (860) 732-5156

PF-06290510 Pfizer staphylococcal infections Phase II (4-antigen Staphylococcus New York, NY (860) 732-5156 aureus vaccine)

vaccine injectable DynPort Vaccine Yersinia infections Phase II Frederick, MD (301) 607-5000 20 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

Preflucel™ Baxter Healthcare prevention of influenza virus Phase III seasonal influenza virus vaccine Deerfield, IL infections (800) 422-9837

Pseudomonas aeruginosa sanofi pasteur prevention of ventilator-associated Phase I antibody fragment product Swiftwater, PA pneumonia (800) 822-2463

PXVX-0103 PaxVax prevention of influenza A virus Phase I (H5N1 ) Menlo Park, CA H5N1 infections www.paxvax.com

Q-LAIV Flu MedImmune seasonal influenza application submitted (MEDI-3250 vaccine) Gaithersburg, MD (301) 398-0000

Quadracel® sanofi pasteur diphtheria, tetanus, pertussis and Phase III diphtheria and tetanus Swiftwater, PA (in children 4-6 years (800) 822-2463 and acellular of age) adsorbed combined with inactivated poliomyelitis vaccine

rabies VRVg sanofi pasteur prevention of rabies infection Phase II (purified vero ) Swiftwater, PA (800) 822-2463

respiratory syncytial virus VLP Novavax prevention of respiratory syncytial Phase I vaccine Rockville, MD virus (RSV) infections (240) 268-2000

RiVax™ Soligenix prevention of ricin poisoning Phase I ricin vaccine Princeton, NJ (609) 538-8200 (Orphan Drug)

sanofi pasteur prevention of rotavirus infections Phase I (live attenuated tetravalent oral Swiftwater, PA (800) 822-2463 vaccine)

rotavirus vaccine I321 Bharat Biotech prevention of rotavirus infections Phase I , India www.bharatbiotech.com

rPA-102 Emergent BioSolutions anthrax Phase II (recombinant protective antigen Rockville, MD (Fast Track) (301) 795-1800 anthrax vaccine)

Shigella vaccine Emergent BioSolutions Shigella infections Phase I Rockville, MD (301) 795-1800

SparVax™ PharmAthene anthrax Phase II completed recombinant protective antigen Annapolis, MD (pre- and post-exposure prevention) (410) 269-2600 (rPA) anthrax vaccine

Staphylococcus aureus vaccine Novartis Vaccines & Diagnostics staphylococcal infections Phase I Cambridge, MA (617) 871-7000

Medicines in Development Vaccines 2012 21 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

Staphylococcus aureus vaccine GlaxoSmithKline Gram-positive infections, Phase I/II conjugate pentavalent Rsch. Triangle Park, NC staphylococcal infections (888) 825-5249

streptococcal B vaccine Emergent BioSolutions streptococcal infections Phase I Rockville, MD (301) 795-1800

streptococcal B vaccine Novartis Vaccines & Diagnostics prevention of streptococcal infections Phase II conjugate Cambridge, MA (617) 871-7000

Streptococcus pneumoniae sanofi pasteur meningitis and penumonia Phase I vaccine Swiftwater, PA (800) 822-2463

TCN-032 Theraclone Sciences influenza A virus infections Phase I (mAb vaccine) Seattle, WA (206) 805-1600

TG-4040 Transgene hepatitis C Phase II (vector-based therapeutic Rockville, MD (301) 816-5421 vaccine)

TransVax™ Astellas Pharma US prevention of cytomegalovirus Phase II cytomegalovirus DNA vaccine Deerfield, IL infections (800) 695-4321 (Orphan Drug) Vical (858) 646-1100 San Diego, CA

tuberculosis recombinant sanofi pasteur prevention of tuberculosis Phase I subunit vaccine Swiftwater, PA (800) 822-2463

tuberculosis vaccine Aerus Global TB Vaccine Foundation prevention of tuberculosis Phase I Rockville, MD www.crucell.com Crucell Leiden, Netherlands

tularemia vaccine DynPort Vaccine prevention of tularemia Phase I Frederick, MD (301) 607-5000

TUTI-16 Thymon HIV-1 infection Phase I/II (synthetic lipopeptide vaccine) Short Hills, NJ (973) 467-9558

Typhella™ Emergent BioSolutions prevention of typhoid Phase II completed oral Rockville, MD (301) 795-1800

typhoid vaccine Novartis Vaccines Institute for prevention of typhoid Phase II Global Health (888) 669-6682 Siena, Italy

V114 Merck prevention of pneumococcal Phase II (pneumococcal 15 valent Whitehouse Station, NJ infections (infants) (800) 672-6372 conjugate vaccine)

22 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

V212 Merck prevention of herpes varicella zoster Phase III (heat-treated varicella-zoster Whitehouse Station, NJ (800) 672-6372 virus [VZV] vaccine)

V502 Merck human papillomavirus infections Phase II completed (virus-like particle [VLP] Whitehouse Station, NJ (800) 672-6372 vaccine)

V503 Merck prevention and treatment of human Phase III (virus-like particle [VLP] Whitehouse Station, NJ papillomavirus infections (800) 672-6372 vaccine) (see also cancer)

V505 Merck prevention of human papillomavirus Phase II completed Whitehouse Station, NJ infections (800) 672-6372 (see also cancer)

V520/V526 Merck HIV infection Phase I combination vaccine Whitehouse Station, NJ (800 672-6372

Vacc-4x Bionor Pharma HIV-1 infections Phase II Oslo, Norway www.bionorpharma.com

VAX-102 VaxInnate prevention of influenza A virus Phase I/II (recombinant fusion protein) Cranbury, NJ infections (609) 860-2260

VAX-125 VaxInnate prevention of influenza A virus Phase II completed (recombinant fusion protein) Cranbury, NJ infections (609) 860-2260

VAX-128 VaxInnate prevention of influenza A virus H1N1 Phase I (recombinant fusion protein) Cranbury, NJ subtype (609) 860-2260

VGX-3100 Inovio Pharmaceuticals human papillomavirus infections Phase II Blue Bell, PA (see also cancer) (877) 446-6846

VGX-3400 Inovio Pharmaceuticals prevention of influenza A virus H5N1 Phase I Blue Bell, PA subtype (877) 446-6846

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

VLP-based influenza vaccine Novavax prevention of influenza virus Phase II (quadrivalent) Rockville, MD infections (240) 268-2000

VLP-based influenza vaccine Novavax prevention of influenza virus Phase II (trivalent) Rockville, MD infections (240) 268-2000

Medicines in Development Vaccines 2012 23 Medicines in Development for Vaccines

Infectious Diseases

Product Name Sponsor Indication Development Status

VRC-EBOADV018-00-VP Vical prevention of Ebola virus infections Phase I completed (Ebola virus DNA vaccine) San Diego, CA (858) 646-1100 Vaccine Research Center Bethesda, MD

VRC-HIVADV014-00-VP GenVec prevention of HIV infection Phase II (HIV-1 recombinant adenovirus Gaithersburg, MD (877) 943-6832 vaccine) Vaccine Research Center (NIAID) www.vrc.nih.gov Bethesda, MD

VRC-HIVADV027-00-VP GenVec prevention of HIV infection Phase I (HIV adenovector Ad35 vaccine) Gaithersburg, MD (877) 943-6832 Vaccine Research Center (NIAID) www.vrc.nih.gov Bethesda, MD

VRC-HIVDNA016-00-VP Vaccine Research Center (NIAID) prevention of HIV infection Phase II (HIV adenovector Ad35 vaccine) Bethesda, MD www.vrc.nih.gov Vical (858) 646-1100 San Diego, CA

XRX-001 Xcellerex prevention of yellow fever Phase I () Marlborough, MA (508) 480-9235

Zostavax® Merck prevention of herpes varicella zoster Phase I zoster vaccine live Whitehouse Station, NJ (800) 672-6372 (intradermal)

Neurological Disorders

Product Name Sponsor Indication Development Status

ACC-002 Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase 0 (immunotherapeutic vaccine) South San Francisco, CA (888) 381-4595 Pfizer (860) 732-5156 New York, NY

AD02 vaccine Affiris Alzheimer’s disease Phase II (amyloid-beta targeting subunit Vienna, Austria www.affiis.com vaccine) GlaxoSmithKline (888) 825-5249 Rsch. Triangle Park, NC

AD03 vaccine Affiris Alzheimer’s disease Phase I completed (amyloid-beta targeting vaccine) Vienna, Austria www.affiris.com GlaxoSmithKline (888) 825-5249 Rsch. Triangle Park, NC

BHT-3009 Bayhill Therapeutics multiple sclerosis Phase II (DNA vaccine) Palo Alto, CA (650) 320-2800

24 Medicines in Development Vaccines 2012 Medicines in Development for Vaccines

Neurological Disorders

Product Name Sponsor Indication Development Status

CAD106 Cytos Biotechnology Alzheimer’s disease Phase II (immunotherapeutic vaccine) Zurich, Switzerland (888) 669-6682 Novartis Pharmaceuticals East Hanover, NJ

UB-311 United Biomedical Alzheimer’s disease Phase I (immunotherapeutic vaccine) Hauppauge, NY (631) 273-2828

V950 Merck Alzheimer’s disease Phase I Whitehouse Station, NJ (800) 672-6372

vanutide cridificar Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase II (amyloid-beta [Aβ] peptide South San Francisco, CA (800) 817-5286 conjugate immunotherapeutic Pfizer (860) 732-5156 vaccine) (ACC-001) New York, NY

Other

Product Name Sponsor Indication Development Status

BHT-3021 Bayhill Therapeutics type 1 diabetes Phase I (DNA vaccine) Palo Alto, CA (650) 320-2800

insulin B-chain vaccine Orban Biotech type 1 diabetes Phase I Brookline, MA (774) 571-2616

NIC002 Cytos Biotechnology Phase II Zurich, Switzerland (888) 669-6682 Novartis Pharmaceuticals East Hanover, NJ

NicVax® Nabi Biopharmaceuticals smoking cessation Phase III conjugate vaccine Rockville, MD (Fast Track) (800) 685-5579

polyclonal antibody stimulator Cancer Advances gastroesophageal reflux disease Phase II Durham, NC (GERD) (919) 361-2162 (see also cancer)

SEL-068 Selecta Biosciences smoking cessation Phase I (nicotine vaccine) Watertown, MA (617) 923-1400

TA-CD Celtic Pharma cocaine abuse Phase II cocaine abuse vaccine Hamilton, Bermuda (212) 616-4000

Medicines in Development Vaccines 2012 25 Glossary

Alzheimer’s disease—Progressive and arthritis. Human infections are acquired by the Haemophilus influenzae—A type of bacteria chronic deterioration of all mental functions. bite of infected Aedes aegypti mosquitoes, and found in the respiratory tract that causes acute Early manifestations include a decrease in at- epidemics are sustained by human-mosquito- respiratory infections and meningitis in children tention span, impaired powers of concentration, human transmission. Chikungunya fever is but rarely in adults. some personality change and forgetfulness. characterized by sudden onset, chills and As the disease progresses, there is a loss of fever, headache, nausea, vomiting, arthralgia, Helicobacter infections—Caused by Heli- computational ability, in addition to word-finding and rash. In contrast to dengue, chikungunya cobacter pylori, a bacterium that is commonly problems and difficulty with ordinary activi- is characterized by the fortunate absence of found in the stomach. It is present in approxi- ties. Ultimately, there is severe memory loss, fatalities. mately one-half of the world’s population. The complete disorientation, social withdrawal, loss vast majority of people infected with H. pylori of independence, and is fatal. It is the seventh Clostridium difficile—A bacterium that pro- have no symptoms and will never develop prob- leading cause of death in the United States. duces an irritating toxin that causes a form of lems; however, H. pylori is capable of causing a colitis characterized by profuse, watery diarrhea number of digestive problems, including ulcers, application submitted—An application for with cramps and low-grade fever. and much less commonly, stomach cancer. It marketing has been submitted to the U.S. Food is not clear why some people with H. pylori get and Drug Administration (FDA). The application cytomegalovirus (CMV)—A DNA virus related these conditions and others do not. can either be an NDA (new drug application) or to the herpes virus, affecting mostly neonatal a BLA (biologic license application). infants and immunocompromised individuals. hematological malignancies—Cancers of CMV can occur without symptoms or result in the blood or bloodforming tissues, such as botulism—A severe, sometimes fatal food mild flu-like symptoms. leukemia, Hodgkin’s and non-Hodgkin’s lym- poisoning caused by ingestion of food con- phomas, AIDS-related malignancies, multiple taining botulin and characterized by nausea, diabetes—A chronic disease due to a distur- myeloma, myelodysplasia and myeloprolifera- vomiting, disturbed vision, muscular weakness, bance of the normal insulin mechanism causing tive disorders. and fatigue. problems in metabolizing sugar. Symptoms may include excessive thirst, hunger, urination and hepatitis—Inflammation of the liver with accom- breast cancer—A malignant tumor that has weight loss. Type 1 is the more severe form, re- panying liver cell damage or death, caused most developed from cells in the breast. It is the quiring insulin treatment. Type 2, in most cases, often by viral infection, e.g., hepatitis B, and C. most common form of cancer in women and is can be controlled by a combination of dietary the second-leading cause of cancer death in measures, weight loss, and oral medication. herpes simplex virus—A strain of herpes virus women, exceeded only by lung cancer. that may lie dormant in nerve tissue and can be Ebola virus—The cause of Ebola hemorrhagic reactivated to produce painful sores of the anus cervical dysplasia—The abnormal growth of (bloody) fever, a severe, often fatal disease in or genitals. cells on the surface of the cervix. Although it humans and nonhuman primates (monkeys, is not cancer, it is considered a precancerous gorillas, and chimpanzees). Researchers herpes varicella zoster virus (HVZ)—Also condition. Most cases of cervical dysplasia believe that the virus is animal-borne (zoonotic) called shingles, consists of very painful blisters occur in women ages 25 to 35, although it can and is normally maintained in an animal host on the skin and affects areas innervated by develop at any age. While all causes of cervical that is native to the African continent. specific nerves. It may appear in adulthood as a dysplasia are not known, most cases of cervical result of having had chicken pox (caused by the cancer and severe dysplasia are caused by glioblastoma—The most common primary varicella virus) as a child. infection of the cervix with a persistent, high-risk brain tumor and one of the most aggressive HIV infection—Presence of in the strain of human papillomavirus (HPV). Cervical forms of brain cancer, primarily affecting adults blood to the human immunodeficiency virus dysplasia is also called cervical intraepithelial over the age of 50. (the virus that causes AIDS). HIV-1 refers to the neoplasia, or CIN. glioma—A type of brain tumor arising from the most common strain of the virus found in U.S. cervical intraepithelial neoplasia—Also called supporting glial cells within the brain. Gliomas AIDS patients. cervical dysplasia, or CIN. make up about 60 percent of all primary brain tumors and are frequently malignant. influenza—A viral infection of the respiratory chikungunya—A disease resembling dengue tract that causes fever, headache, muscle ache fever, seen mainly in Africa, the Indian sub- Gram-positive bacteria—Gram’s stain is a and weakness. There are three main types of continent, and Southeast Asia, caused by an method of staining bacteria in order to identify influenza virus: A, B and C. A person who has arbovirus transmitted by Aedes mosquitoes. them. Gram-positive bacteria stain violet. had an attack with the type C virus acquires an- The most prominent frequent feature is severe tibodies that provide immunity against that type

26 Medicines in Development Vaccines 2012 Glossary

for life. Anyone who has been infected with a lin, penicillin and amoxicillin. Staph infections, patients with compromised immune systems. certain strain of the type A or B viruses acquires including MRSA, occur most frequently among There are four serotypes of HPIV (1 through 4). immunity to that strain. Both the A- and B-type patients in hospitals and healthcare settings. Each of the four HPIVs has different clinical and viruses occasionally alter to produce new epidemiologic features. strains that may be able to overcome immu- multiple myeloma—A malignant condition char- nity. Type B is fairly stable, but type A is highly acterized by uncontrolled proliferation of plasma parvovirus infection—Also called “fifth dis- unstable, and new strains of it arise constantly cells (a class of white blood cells) in bone mar- ease,” which is caused by infection with human throughout the world. row. Symptoms include pain and destruction of parvovirus B19. The virus infects only humans, bone tissue, numbness and paralysis, kidney resulting in a mild rash illness that occurs most Japanese encephalitis (JE)—Caused by a damage, anemia, and frequent infections. commonly in children. The ill child typically has virus that is closely related to the West Nile and a “slapped cheek” rash on the face and a lacy Saint Louis encephalitis viruses and is transmit- multiple sclerosis—Progressive disease of red rash on the trunk and limbs. Occasionally, ted to humans through the bite of an infected the central nervous system in which scattered the rash may itch, but it usually resolves in 7 to mosquito. It is the most common vaccine- patches of the covering of nerve fibers (myelin) 10 days. preventable cause of encephalitis in Asia, in the brain and spinal cord are destroyed. occurring throughout most of Asia and parts of Symptoms range from numbness and tingling to Phase 0—First-in-human trials conducted the western Pacific. In endemic countries, JE is paralysis and incontinence. in accordance with FDA’s 2006 guidance on exploratory Investigational New Drug (IND) primarily a disease of children; however, travel- Neisseria meningitidis—The Gram-negative associated JE can occur among people of any studies designed to speed up development of bacterium that causes meningococcal menin- promising drugs by establishing very early on age. The risk for JE for most travelers to Asia is gitis in humans, the only natural hosts in which extremely low but varies based on destination, whether the agent behaves in human subjects it causes disease. Meningococci enter the as was anticipated from preclinical studies. duration, season, and activities. nasal passage and may cause no symptoms malaria—A serious parasitic disease, spread (up to 30 percent of the population may harbor Phase I—Safety testing and pharmacological by the bite of the Anopheles mosquito. Malaria them between epidemics), or they may enter profiling in humans. is characterized by severe fever and chills and the bloodstream and produce the symptoms of meningitis. Phase II—Effectiveness and safety testing in complications affecting the kidneys, liver, brain humans. and blood. noroviruses—A group of viruses that cause the “stomach flu,” or gastroenteritis. Symptoms Phase III—Extensive clinical trials to demon- Marburg virus disease—Also called Marburg strate safety and efficacy in humans. hemorrhagic fever, a rare, severe type of usually include nausea, vomiting, diarrhea, and hemorrhagic fever that affects both humans and some stomach cramping. Sometimes people pneumococcal infections—Caused by nonhuman primates. It is caused by a genetical- also have a low-grade fever, chills, headache, Streptococcus pneumoniae, or pneumococcus, ly unique animal-borne (zoonotic) RNA virus of muscle aches, and tiredness. The illness often a Gram-positive human pathogenic bacterium. the filovirus family. Marburg virus is indigenous begins suddenly and lasts for one or two days. The organism causes many types of pneumo- to Africa, including parts of Uganda, Western papillomavirus—The papillomavirus is the coccal infections, including pneumonia, otitis Kenya, and Zimbabwe. viral agent of warts, believed to be contagious media, meningitis, sepsis, endocarditis, and brain abscess. S. pneumoniae is the most com- meningococcal disease—Describes infections and mostly harmless, affecting only the skin’s topmost layer. mon cause of bacterial meningitis in adults and caused by the bacterium Neisseria menin- children and one of the top two isolates found gitides. It carries a high mortality rate if left parainfluenza viruses—Human parainfluenza in ear infection (otitis media). Pneumococcal untreated. While it is best known as a cause viruses (HPIVs) rank second only to respira- pneumonia is more common in the very young of meningitis, it also causes widespread blood tory syncytial virus (RSV) as a common cause and the very old. infection (sepsis), which is more damaging and of lower respiratory tract disease in young dangerous. Both meningitis and meningococcal children. HPIVs can cause repeated infections prostate cancer—An uncontrolled (malignant) sepsis are major causes of illness, death, and throughout life, which are usually manifested growth of cells in the prostate gland that is disability worldwide. by an upper respiratory tract illness (such as a located at the base of the urinary bladder and is cold or sore throat). HPIVs can also cause seri- responsible for helping control urination as well MRSA (methicillin-resistant Staphylococcus as forming part of the semen. Prostate cancer aureus)—A type of bacteria that is resistant ous lower respiratory tract disease with repeat infection (including pneumonia, bronchitis, and is the second leading cause of death of males to certain antibiotics, including methicillin and in the United States. other more common antibiotics such as oxacil- bronchiolitis), especially among the elderly and

Medicines in Development Vaccines 2012 27 Glossary

rotavirus—A group of viruses that are wheel- hands and forearms, and later on the trunk. The blood infections, skin infections, and pneumonia like in appearance and are a major source of distribution of lesions is a hallmark of smallpox in adults. infant diarrhea throughout the world. and a primary way of diagnosing the disease. tuberculosis—An infectious disease caused sarcoma—A malignant tumor that arises from staphylococcal infections—Caused by Staph- by the organism Mycobacterium tuberculosis, deep body tissues, such as muscle, bone or ylococcus bacteria, which are germs commonly which is passed from person to person by fibrous tissue. found on the skin or in the nose of healthy breathing in airborne droplets (from cough- individuals. Most of the time, these bacteria ing or sneezing). The bacteria multiply in the Shigella—A family of bacteria that can cause cause no problems or result in relatively minor lungs and in some cases can spread to the diarrhea in humans. There are several different skin infections, but staph infections don’t always lymph nodes. A person’s most kinds of Shigella bacteria. One type found in remain skin-deep. In some circumstances, frequently will attack and heal the infection, the developing world, Shigella dysenteriae type they may invade the bloodstream, urinary tract, causing a scar on the lung. 1, causes deadly epidemics there. Shigella lungs or heart. Skin infections caused by staph causes , an infectious disease char- bacteria include: boils, impetigo, cellulitis, and tularemia—Also called “rabbit fever” or “deerfly acterized by (often bloody) diarrhea, fever, and scalded skin syndrome. fever,” caused by the bacterium Francisella stomach cramps. tularensis found in animals (especially rodents, Staphylococcus aureus—A common bacte- rabbits, and hares). It is a potentially serious smallpox—A contagious, disfiguring and often rium that is a frequent cause of hospital infec- illness that can be fatal if not treated with the deadly disease caused by the variola virus. The tions, including pneumonia, surgical wounds, right antibiotics. first symptoms of smallpox usually appear 12 and systemic blood infections. to 14 days after infection. During the incubation varicella zoster—Chicken pox and herpes period of seven to 17 days, an infected person streptococcal infections—There are two zoster are caused by the varicella zoster virus, looks and feels healthy and can’t infect others. types of “strep” infections—group A and group chicken pox being the acute invasive phase Following the incubation period, a sudden onset B—both of which are treated by antibiotics. of the virus and zoster (shingles) being the of flu-like signs and symptoms occurs, including Group A strep causes strep throat, scarlet fever, reactivation of the latent stage. fever, headache, severe fatigue, and some- impetigo, toxic shock syndrome, cellulitis, and times vomiting, diarrhea or both. A few days necrotizing fasciitis (flesh-eating disease). Yersinia—Three Gram-negative bacilli Yersinia later, the characteristic smallpox rash appears Group B can cause blood infections, pneumo- species cause infection in humans: Y. enteroco- as flat, red spots (lesions). Within a day or two, nia, and meningitis in newborns. Adults can litica causes gastroenteritis; Y. pseudotubercu- many of these lesions turn into small blisters also get group B strep infections, especially if losis causes mesenteric lymphadenitis; and Y. filled with clear fluid (vesicles) and later with pus they are elderly or already have health prob- pestis causes plague. (pustules). The rash appears first on the face, lems. Strep B can cause urinary tract infections,

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28 Medicines in Development Vaccines 2012 Facts About Recommended Vaccines in the United States

Overview

• The current U.S. schedule for children between birth and age 6 recommends for 14 different diseases. Each disease for which are recommended can cause serious illness or death in unvaccinated populations, and those diseases might quickly begin to appear again if vaccination rates drop. The United States has seen mumps outbreaks in recent years since vaccination rates have dropped, with severe complications and hospitalizations required for some patients. And before the introduction of the Hib (Haemophilus infuenzae type b) vaccine, Hib meningitis affected more than 12,000 American children annually, killing 600 and leaving many others with seizures, deafness, and developmental disabilities. After introduction of the vaccine, the number of deaths from Hib dropped to fewer than 10 per year. Each vaccine on the schedule continues to be recommended because of the risks posed by wild infection (virus from a naturally infected animal, as opposed to a laboratory-adapted strain of the virus).

• The effectiveness of most vaccines is high. After receiving the second dose of the MMR vaccine (measles, mumps and rubella) or the stand-alone , 99.7 percent of vaccinated individuals are immune to measles. The inactivated polio vaccine offers 99 percent effectiveness after three doses. The varicella (chickenpox) vaccine is between 85 percent and 90 percent effective in preventing all varicella infections, but 100 percent effective in preventing moderate and severe chicken pox.

• While in some cases natural immunity is longer-lasting than the immunity gained from vaccination, the risks of natural infection outweigh the risks of for every recommended vaccine. For example, wild measles infection causes encephalitis (inflammation of the brain) for one in 1,000 infected individuals. Overall, measles infection kills two of every 1,000 infected individuals. In contrast, the combination MMR (measles, mumps and rubella) vaccine results in a severe allergic reaction only once in every million vaccinated individuals, while preventing measles infection. The benefits of vaccine-acquired immunity extraordinarily outweigh the serious risks of natural infection.

• Before the became available, chickenpox infections resulted in 10,000 hospitalizations and caused more than 100 deaths each year in the United States. Even uncomplicated cases of chickenpox cause children to miss a week or more of school, with a caregiver missing work to care for the sick child.

Diseases Covered by Vaccines in the United States

• Diphtheria once was a major cause of illness and death among children. The United States recorded 206,000 cases of diphtheria in 1921, re- sulting in 15,520 deaths (a case-fatality ratio of 7.5 percent). Diphtheria death rates range from about 20 percent for those under age 5 and over age 40 to 5 percent – 10 percent for those ages 5 – 40. Since the introduction of effective immunization, starting in the 1920s, diphtheria rates have dropped dramatically in the United States and other countries that vaccinate widely. Between 2004 and 2008, no cases of diphtheria were recorded in the United States. While the reach of diphtheria immunization expanded when the World Health Organization included diphtheria toxoid in its list of recommended immunizations for its Expanded Programme on Immunization for developing countries in 1974, the disease con- tinues to play a role globally. In 2007, 4,190 cases of diphtheria were reported worldwide, which is likely an underestimate of the actual number of cases.

• Haemophilus infuenzae type b, commonly known as Hib, is a bacterium that can cause severe infections, particularly in young children. Hib bacteria can cause many types of invasive disease, including meningitis, pneumonia, cellulitis (skin infection), septic arthritis (joint infection) and epiglottitis (infection of the epiglottis, causing obstruction or closing of the windpipe). The vaccine protects against the diseases caused by Hib, which are numerous and can be severe. Collectively, these Hib-caused infections are referred to generally as “Hib disease.” Before the Hib vac- cine was introduced in 1985, about 20,000 children younger than age 5 developed severe Hib disease in the United States each year, and about 1,000 died. By 2006, the number of reported Hib cases was down to only 29 for the year. Today, the majority of fatalities from Hib disease are reported in developing countries where the Hib vaccine is not widely used, but fatalities still occur in developed nations when vaccination rates drop. For example, seven cases of invasive Hib disease were reported in Pennsylvania during a six month period starting in October 2008. Only one of the children had received a Hib vaccination (and had only received one of the recommended doses). Three of the children died.

Medicines in Development Vaccines 2012 29 Facts About Recommended Vaccines in the United States

Diseases Covered by Vaccines in the United States (continued)

• Hepatitis , a general term for inflammation of the liver, may result from infectious or non-infectious causes. Viruses responsible for many cases of infectious hepatitis include hepatitis A, hepatitis B, hepatitis C, hepatitis D, and . Hepatitis A and B are the only hepatitis viruses for which vaccines are currently available (although immunity for hepatitis B also confers immunity for hepatitis D). No specific treatments exist for acute hepatitis A and B infections. Both hepatitis A (HAV) and hepatitis B (HBV) infection can have immediate, deadly consequences. Approximately 1 percent of people with acute HBV infections will suffer acute liver failure. HAV infection may also, though less commonly than HBV infection, lead to liver failure. Up to 90 percent of patients with acute liver failure will die. Up to 95 percent of adults infected with acute HBV infection recover and do not become chronically (permanently) infected, although they can infect other people during the acute phase via trans- mission of body secretions. The others become chronically infected—and able to infect others for a much longer time (in some cases for many years)—and are at risk for serious liver disease. Infants and children who become infected with hepatitis B are much more likely than adults to become chronically infected and hence to develop serious, late complications. Chronic infection with HBV may lead to cirrhosis, liver failure, and liver cancer. The FDA has licensed several hepatitis B and hepatitis A vaccines for use in the United States, including several combination vac- cines. They have been part of the routine childhood immunization schedule since 1994.

• Human papillomaviruses (HPV) belong to a large family of viruses, only some of which are sexually transmitted. Certain types of HPV cause genital warts. Other HPV types are the main cause of cervical cancer, and some are associated with anal, penile, mouth, and throat cancers. HPV is very common: one recent study showed that nearly 27 percent of women ages 14-59 tested positive for one or more strains of HPV. Rates for men are likely to be similar. Other models have shown that more than 80 percent of women will have been infected with genital HPV by the time they reach age 50. The U.S. Food and Drug Administration approved (HPV4), a vaccine for four types of HPV, in 2006. FDA approved another vaccine, (HPV2) that protects against two types of HPV, in 2009. The recommended age for HPV vaccination of females is 11-12 years. The vaccine can be administered as young as age 9. Catch-up vaccination is recommended for females ages 13-26 who have not been previously vaccinated. The 3-dose series of HPV4 may be given to males ages 9 through 26 to reduce their likelihood of acquiring genital warts. HPV4 would be most effective when given before exposure to HPV through sexual contact.

• Influenza is a respiratory illness caused by influenza viruses. There are two main types of influenza viruses (A and B) but many different strains of each type. New strains of influenza viruses appear frequently, and previous infection with a different strain does not guarantee immunity against future infection. That is one reason why new versions of the seasonal flu vaccine are created each year—to try to protect against which- ever flu strains are currently circulating. Pneumonia is the most commonly seen complication of influenza infection.The flu can also lead to sinus and ear infections, worsen existing medical conditions such as chronic pulmonary diseases, or cause inflammation of the heart.Although any flu patient can experience complications from the disease, certain groups are at a higher risk for flu complications than others, including older indi- viduals, young children, people with asthma, and pregnant women. In a typical flu season, people 65 or older account for 90 percent of deaths from the flu. Some pandemic influenzas behave quite differently than expected in this regard; in the 2009 H1N1 pandemic, almost 90 percent of deaths from H1N1 influenza were among people younger than 65.

• Measles is an extremely contagious disease caused by a virus and spread through the air. Its symptoms include fever (which may rise to 104o F or higher) and coughing as well as its infamous rash. Measles can lead to complications ranging in severity from diarrhea to encephalitis (swelling of the brain), with adult patients typically being subject to more severe complications. Although the disease is rarely fatal in developed countries, the death rate can be quite high in underdeveloped nations. Case-fatality rates have been recorded as high as 28 percent and tend to rise during wars or widespread food shortages. As recently as 2000, measles caused 1.1 million deaths globally among young children in a year’s time. A vaccine to protect against measles was developed in the 1960s and was quickly adopted. Widespread vaccination programs, including the Measles Initiative launched in 2001 by the American Red Cross, the United Nations Foundation, the U.S. Centers for Disease Control and Prevention, UNICEF and the World Health Organization, contributed to global decreases in measles cases until the case count among children fell as low as 118,000 by 2008. Since 2008, however, vaccination campaigns have suffered from funding cutbacks, allowing the highly contagious disease to roar back. Despite the cost of vaccinating a child against measles being less than $1, according to the World Health Organization, outbreaks have been reported in 30 African countries as well as Thailand, Bulgaria, Indonesia and Vietnam.

30 Medicines in Development Vaccines 2012 Facts About Recommended Vaccines in the United States

Diseases Covered by Vaccines in the United States (continued)

• Neisseria meningitidis bacteria, also called meningococcus [meningococci (plural)], is an important cause of bacterial meningitis and sepsis (bloodstream infection) in the United States. Meningococci can also cause pneumonia, otitis media (ear infection), arthritis, and other infections, although they are less common. Collectively, the different illnesses caused by N. meningitidis are referred to as meningococcal disease. Although meningococcal epidemics do not occur on a national level in developed countries, there is a risk to travelers who visit parts of the world where epidemics occur regularly. The highest risk region for epidemic meningococcal disease is sub-Saharan Africa. In the United States, between 1,400 and 2,800 cases of meningococcal disease occur each year. Invasive meningococcal disease can be fatal: even with antibiotic treatment, the mortality rate ranges from between 9 percent to 12 percent. Up to 20 percent of survivors of invasive meningococcal disease have permanent injury, including brain damage, hearing loss, or loss of a limb. The first conjugate meningococcal vaccine in the United States, MCV4 (Menactra), was licensed in 2005 (for ages 2 to 55), with a second, MenACWY-CRM (Menveo), licensed in 2010 (for ages 11 to 55).

• Mumps are caused by a virus, and its symptoms include low-grade fever, respiratory problems, and most notably swelling of the salivary (parot- id) glands below the ear, known as parotitis. While parotitis is the most easily recognized symptom of mumps, it occurs only in about 30 percent to 40 percent of cases. Up to 20 percent of infected individuals may experience no symptoms at all. In the United States, cases of mumps have dropped by 99 percent since the introduction of a vaccine in 1967. Unlike measles and rubella, however, mumps has not yet been eliminated in the United States. Recent large outbreaks have occurred among college students (in 2006, more than 6,500 cases) and in a tradition-observant Jewish community, sparked by a boy who returned from a trip to the United Kingdom and began showing symptoms of mumps while at a sum- mer camp (from 2009-2010, more than 3,400 cases).

• Pertussis, also known as whooping cough, is an extremely contagious disease caused by a bacterium that produces toxins which paralyze parts of respiratory cells, leading to inflammation in the respiratory tract.After symptoms first appear, the disease can take anywhere from weeks to months to fully run its course. Eventually the patient experiences bouts of rapid coughing followed by the “whooping” sound that gives the disease its common name as they try to inhale. Pertussis can be extremely dangerous for infants and young children, with the highest percent- age of complications occurring in children less than 6 months of age. The most common complication is bacterial pneumonia, which is also the most common cause of deaths from pertussis. Although cases of pertussis have dropped dramatically in the United States since the introduction of the pertussis vaccine, the disease has caused widespread outbreaks when vaccination rates have dropped. A recent outbreak in California led to the deaths of five infants in the first six months of 2010. Pertussis also remains a major problem in the developing world, with estimates from the World Health Organization attributing nearly 280,000 deaths to the disease worldwide in 2003.

• Streptococcus pneumoniae bacteria, also called pneumococcal bacteria, are one of the leading causes of illness in young children. At least 90 types of pneumococcal bacteria are known to exist. They can cause pneumonia as well as bloodstream infections (bacteremia), meningitis, sinusitis, and middle ear infection, among other illnesses. Collectively, the different illnesses caused by Streptococcus pneumoniae are referred to as pneumococcal disease. Invasive pneumococcal disease can be fatal; survivors of meningitis may have permanent injury, including brain damage, seizures, or hearing loss. Each year in the United States, pneumococcal bacteria cause more than 4,800 cases of invasive pneumo- coccal disease in children younger than age 5. Among this group, about 5 percent die from the infection. Of those who survive, some are left with permanent injury. Pneumococcal bacteremia (bloodstream infection) cases total more than 50,000 each year in the United States (bacteremia occurs in approximately 25 percent of all pneumococcal pneumonia cases). The mortality rate for those with pneumonia complicated by bactere- mia is approximately 20 percent, but may be as high as 60 percent for elderly patients. Pneumococcal meningitis cases total about 3,000 each year in the United States, and the mortality rate ranges from 10 percent to 30 percent. Pneumococcal pneumonia causes an estimated 175,000 hospitalizations each year in the United States, and has a case-fatality ratio of up to 7 percent (in the elderly, that figure is higher). Pneumo- coccus is the cause of up to 36 percent of community-acquired pneumonia cases, and 50 percent of community-acquired cases that require hospitalization. A pneumococcal vaccine that protected against 14 different strains was licensed in 1977 and was expanded to protect against 23 strains in 1983. However, it is most effective in adults. A separate vaccine for children was licensed in 2000 and was expanded to include protec- tion against 13 strains in 2010. Since the initial recommendation, invasive pneumococcal disease in children has dropped by nearly 80 percent in the United States.

Medicines in Development Vaccines 2012 31 Facts About Recommended Vaccines in the United States

Diseases Covered by Vaccines in the United States (continued)

• Few diseases frightened parents more in the early part of the 20th century than did polio (the common name for poliomyelitis). Polio struck in the warm summer months, sweeping through a few towns as an epidemic every few years. Though most people recovered quickly from polio, some suffered temporary or permanent paralysis and even death. Many polio survivors were disabled for life. Polio has no cure, so prevention is the most effective means to combat it. In about 95 percent of all polio cases, the person has no symptoms at all. The rest of polio cases can be divided into three types: abortive polio (mild illness), non-paralytic polio (mild illness with neurological symptoms), and paralytic polio (includes the first signs of paralysis). Fewer than 1 percent to 2 percent of people who contract polio become paralyzed. In most cases of paralytic polio, the patient recovers completely. However, for a certain number of people, paralysis or muscle weakness remains for life. In severe cases of paralytic polio, the throat and chest may be paralyzed. Death may result if the patient does not receive artificial breathing support. Between 2 percent to 5 percent of children affected with paralytic polio die; for adults,15 percent to 30 percent die. Because of widespread vaccination, polio was eliminated from the Western Hemisphere in 1994. Today, it continues to circulate in a handful of countries, with occasional spread to neighboring countries. (Endemic countries are , India, Nigeria, and Pakistan.) Vigorous vaccination programs are being conducted to eliminate these last pockets. Polio vaccination is still recommended worldwide because of the risk of imported cases.

• Rotavirus is the most common cause of severe diarrhea in children and infants worldwide. Before a vaccine was introduced in the United States, the disease caused more than 400,000 doctor visits and 200,000 emergency room visits each year, resulting in as many as 60 deaths annually in children younger than age 5. Globally, rotavirus kills more than 500,000 children under age 5 each year, with most deaths occurring in developing countries. In 2006, the newly licensed rotavirus vaccine RotaTeq was recommended as routine infant immunization and in 2008, the Food and Drug Administration licensed another rotavirus vaccine, Rotarix, for use in infants in the United States. The CDC has carefully monitored incidence of rotavirus disease in the United States since 2000. Their studies show that the number of positive test results for rotavirus was substantially lower than the median observed during 2000-2006. Additionally, it appears that hospitalization rates for acute gastroenteritis dropped by 16 percent in 2007 and by 45 percent in 2008 compared with the earlier period. Researchers have estimated that rotavirus vaccina- tion prevented about 55,000 hospitalizations in 2008.

• Rubella is caused by a virus, and although rubella is sometimes called “German measles,” the rubella virus is not related to the measles virus. Rubella symptoms include low-grade fever, respiratory problems, and most notably a rash of pink or light red spots. In children, illness from ru- bella infection is usually mild. Complications from rubella are more common in adults. A woman who contracts rubella infection during pregnancy can pass the infection to the developing fetus. Such pregnancies are at risk of spontaneous abortion or premature birth. If the fetus survives, the child may suffer from a wide range of birth defects, including deafness, eye defects, cardiac defects, mental retardation, bone lesions, and other abnormalities. Together, the defects are known as congenital rubella syndrome (CRS), which is the chief danger of rubella disease. Of children whose mothers are infected during their first trimester of pregnancy, studies suggest that between 50 percent and 90 percent will suffer from CRS. From 1964-1965, before the development of a vaccine against the disease, a rubella epidemic swept the United States. During that short period, 12.5 million cases of rubella developed, and 20,000 children were born with CRS: 11,000 were deaf, 3,500 blind, and 1,800 mentally retarded. There were 2,100 neonatal deaths and more than 11,000 abortions—some a spontaneous result of rubella infection in the mother and others performed surgically after women were informed of the serious risks of rubella exposure during their pregnancy. As of 2004, rubella was declared eliminated in the United States, and transmission of the rubella virus in the World Health Organization’s Region of the Americas was halted in 2009. Globally, about 75,000 rubella cases were reported for 2010 in the member states to the World Health Organization, though it is probable that the number of actual cases is higher.

• The history of smallpox, which is caused by a virus, holds a unique place in human health and medicine. One of the deadliest diseases known to humans, smallpox is also the only disease to have been eradicated by vaccination. Some estimates indicate that worldwide deaths from smallpox numbered more than 300 million during the 20th century. The last U.S. wild smallpox case occurred in 1949. After intensive vaccination campaigns in the 1960s and 1970s, the last case of wild smallpox in the world occurred in Somalia in 1977. (Today, certain U.S. military person- nel and some civilian workers receive the smallpox vaccine due to the threat of .)

32 Medicines in Development Vaccines 2012 Facts About Recommended Vaccines in the United States

Diseases Covered by Vaccines in the United States (continued)

• Tetanus is a disease of the nervous system caused by bacteria that produces two exotoxins, one of which is a neurotoxin that causes the symptoms of tetanus: lockjaw (the most recognizable of its physical effects), stiffness, and problems swallowing. Later symptoms include severe muscle spasms, seizure-like activity, and severe nervous system disorders. Generally, between 10 percent and 20 percent of tetanus cases re- sult in death, though fatalities are more likely among patients older than age 60 and among unimmunized individuals. In the most common type of reported tetanus (“generalized tetanus”), spasms continue for 3-4 weeks, and recovery may take months. The extreme rarity of tetanus cases among individuals immunized up to 10 years prior to infection suggests an efficacy rate of nearly 100 percent for the . Immunity levels do decrease with time, however, so that boosters against tetanus are recommended every 10 years in order to maintain protection against the disease. A tetanus booster is recommended for individuals who sustain any wound that is not clean and minor if more than 5 years have passed since their last dose of tetanus toxoid.

• Yellow fever is a viral disease spread between humans, as well as between certain other primates and humans, by the bite of infected mos- quitoes. Yellow fever is endemic in areas of Latin America and Africa, while imported cases have appeared throughout the world. Globally, the disease infects about 200,000 people per year, causing fever, chills, nausea, vomiting, muscle pain, and headache, and has no cure. While many yellow fever patients recover after 3-4 days of symptoms, approximately 15 percent enter a second phase of the illness after a remission. The second phase includes a return of high fever, as well as jaundice; abdominal pain and vomiting; bleeding from the mouth, nose, eyes, or stomach; and deteriorating kidney function. Up to half of the patients who experience the second phase may die. In all, yellow fever kills 30,000 people globally each year. The yellow fever vaccine provides protection for 30 years or more—possibly for life—and for 95 percent of those vaccinated, offers protective immunity against the disease within a week. Yellow fever vaccination is typically performed only in areas where the disease is endemic, but it is available (and sometimes required) for those traveling to regions where the virus is still widespread. The most recent statistics from the World Health Organization showed immunization coverage of approximately 51 percent in 2007 in countries considered at risk for outbreaks. That is a vast increase from 1988, when the disease was at its modern peak with more than 5 million cases reported globally and immunization coverage of less than 5 percent.

Source:

“The History of Vaccines,” A Project of the College of Physicians of Philadelphia (www.historyofvaccines.org)

Medicines in Development Vaccines 2012 33 The Drug Discovery, Development and Approval Process

It takes 10-15 years on average for an experimental drug to travel from the lab to U.S. patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved.

The Drug Development and Approval Process The U.S. system of new drug approvals is Administration (FDA) to begin to test the drug hospitals. Physicians monitor patients closely to perhaps the most rigorous in the world. in people. The IND shows results of previous confirm efficacy and identify adverse events. experiments; how, where and by whom the It takes 10-15 years, on average, for an New Drug Application (NDA)/Biologic new studies will be conducted; the chemical experimental drug to travel from lab to U.S. License Application (BLA). Following the structure of the compound; how it is thought patients, according to the Tufts Center for the completion of all three phases of clinical trials, to work in the body; any toxic effects found in Study of Drug Development. Only five in 5,000 a company analyzes all of the data and files an the animal studies; and how the compound compounds that enter preclinical testing make NDA or BLA with FDA if the data successfully is manufactured. All clinical trials must be it to human testing. And only one of those five demonstrate both safety and effectiveness. reviewed and approved by the Institutional is approved for sale. The applications contain all of the scientific Review Board (IRB) where the trials will be information that the company has gathered. On average, it costs a company $1.2 billion, conducted. Progress reports on clinical trials Applications typically run 100,000 pages or including the cost of failures, to get one new must be submitted at least annually to FDA and more. medicine from the laboratory to U.S. patients, the IRB. according to a 2007 study by the Tufts Center Approval. Once FDA approves an NDA or Clinical Trials, Phase I. These tests usually for the Study of Drug Development. BLA, the new medicine becomes available involve about 20 to 100 healthy volunteers. The for physicians to prescribe. A company must Once a new compound has been identified in tests study a drug’s safety profile, including the continue to submit periodic reports to FDA, the laboratory, medicines are usually devel- safe dosage range. The studies also determine including any cases of adverse reactions and oped as follows: how a drug is absorbed, distributed, metabo- appropriate quality-control records. For some lized, and excreted as well as the duration of Preclinical Testing. A pharmaceutical com- medicines, FDA requires additional trials its action. pany conducts laboratory and animal studies (Phase IV) to evaluate long-term effects. to show biological activity of the compound Clinical Trials, Phase II. In this phase, Discovering and developing safe and effective against the targeted disease, and the com- controlled trials of approximately 100 to 500 new medicines is a long, difficult, and expensive pound is evaluated for safety. volunteer patients (people with the disease) process. PhRMA member companies invested assess a drug’s effectiveness and determine Investigational New Drug Application (IND). an estimated $49.5 billion in research and the early side effect profile. After completing preclinical testing, a company development in 2011. files an IND with the U.S. Food and Drug Clinical Trials, Phase III. This phase usually involves 1,000 to 5,000 patients in clinics and