PhRMA Report 2012: Medicines in Development for HIV/AIDS

Biopharmaceutical research companies are developing 73 medicines and vaccines, focusing on improved treatment regimens, more effective therapies and promising new preventative vaccines.

Although HIV/AIDS is one of the most devastating diseases affecting people around the world, the number of new infections has been steadily declining. In the United States, the AIDS-related death rate has fallen by 79 percent due to antiretroviral therapy.

Over the past 30 years, nearly 40 medicines have been approved to treat HIV/AIDS. Testing for the disease also has advanced dramatically, enabling earlier treatment. While these medicines have helped to prolong the lives of HIV-infected patients, making HIV a manageable chronic disease, opportunities for even greater progress remain.

For example, biopharmaceutical companies are intensifying their efforts to develop vac-cines that would help prevent HIV. Current estimates show that a 50 percent effective

vaccine given to only a third of the population could reduce new HIV infections by 24 percent over 15 years.

The medicines in the development pipeline include:

• A gene therapy that uses genetic material to remove disease-causing aspects of the virus.

• A transdermal vaccine that helps suppress vi-rus replication and destroys HIV-infected cells.

• A first-in-class medicine intended to prevent the HIV virus from breaking through the cell membrane.

Despite the incredible progress to date, the HIV/AIDS epidemic remains a complex prob-lem. America’s biopharmaceutical research companies are continuing their efforts to de-velop novel and more effective therapies, vac-cines to prevent the disease, and potentially a cure, so the millions of patients suffering today have hope for a better tomorrow.

Biopharmaceutical Researchers Are Testing More Than 70 Medicines and Vaccines For HIV Infection

Medicines in Development

HIV/AIDSpresented by america’s biopharmaceutical research companies

2012 RepoRt

40

4 4

25

Vacc

ines

Cel

l/Gen

e Th

erap

y

Imm

unom

odul

ator

s

Antiv

irals

28

35

25

Uns

peci

fied

4

Appl

icat

ion

Subm

itted

Phas

e II

Phas

e III

Phas

e I

Medicines in Development for HIV/AIDS

Medicines in Development for HIV/AIDS by Phase of Development

* Some medicines are listed in more than one phase of development.

1.2 million Americans are living with HIV, 50,000 are newly diagnosed each year

Medicines in Development HIV/AIDS 20122


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

AntIVIrAlS

product Name Sponsor Indication Development Status*

abacavir/dolutegravir/lamivudinefixed-dose combination(integrase inhibitor/reverse transcriptase inhibitor)

ViiV HealthcareRsch. Triangle Park, NC

HIV infection therapy in treatment-naive patients

Phase III(877) 844-8872

amdoxovir (DAPD) RFS PharmaTucker, GA

HIV-1 infection treatment Phase II(404) 601-1430

BI-224436(integrase inhibitor)

Gilead SciencesFoster City, CA

HIV infection treatment Phase I completed(800) 445-3235

CB1922(synthetic steroidal lactone)

Canopus BioPharmaStudio City, CA

HIV infection treatment Phase IIwww.canopusbiopharma.com

cenicriviroc(CCR5 receptor antagonist)

Tobira TherapeuticsSouth San Francisco, CA


CMX157(tenofovir PIM conjugate)

MerckWhitehouse Station, NJ

HIV infection treatment Phase I completed(800) 672-6372

cobicistat(PK enhancer)


HIV infection treatment application submitted(800) 445-3235

cobicistat/darunavirfixed-dose combination(PK enhancer/protease inhibitor)

Gilead SciencesFoster City, CAJanssen TherapeuticsTitusville, NJ

HIV infection Phase I(800) 445-3235(800) 526-7736

cobicistat/darunavir/emtricitabine/GS-7340 fixed-dose combination

Gilead SciencesFoster City, CAJanssen TherapeuticsTitusville, NJ

HIV-1 infection Phase II(800) 445-3235(800) 526-7736

cobicistat/elvitegravir/emtricitabine/GS-7340 fixed-dose combination


HIV-1 infection Phase II(800) 445-3235

dapivirine(NNRTI)

International Partnership forMicrobicidesSilver Spring, MD

HIV infection prevention(vaginal ring)--------------------------------------------------HIV infection prevention(vaginal gel)

Phase I/II completed(301) 608-2221-------------------------------------------Phase I/II completed(301) 608-2221

dolutegravir(S/GSK1349572)(integrase inhibitor)

ShionogiFlorham Park, NJViiV HealthcareRsch. Triangle Park, NC

HIV-1 infection treatment Phase III(973) 966-6900(877) 844-8872

Medicines in Development HIV/AIDS 2012 3


AntIVIrAlS

product Name Sponsor Indication Development Status

efavirenz/lamivudine/tenofovir fumarate fixed-dose combination

Mylan LaboratoriesCanonsburg, PA

HIV-1 infection treatment application submitted(724) 514-1800

elvitegravir(integrase inhibitor)


HIV-1 infection treatment application submitted(800) 445-3235

elvucitabine(NRTI)

Achillion PharmaceuticalsNew Haven, CT

HIV infection treatment Phase II(203) 624-7000

GS-7340(NtRTI)



HIV attachment inhibitor Bristol-Myers SquibbPrinceton, NJ


HIV maturation inhibitor Bristol-Myers SquibbPrinceton, NJ

HIV infection treatment in clinical trials(800) 332-2056

ibalizumab(TMB-355)(fusion inhibitor)

TaiMed Biologics USAIrvine, CA

HIV-1 infection treatment(intravenous) (Fast Track)--------------------------------------------------HIV-1 infection treatment(subcutaneous)

Phase II(949) 769-6543-------------------------------------------Phase I(949) 769-6543

Intelence®

etravirine(NNRTI)

Janssen TherapeuticsTitusville, NJ

HIV infection combination therapy in treatment-naive patients(Fast Track)

Phase II(800) 526-7736

KD-247(monoclonal antibody)

KaketsukenKumamoto, Japan

HIV-1 infection treatment Phase Iwww.kaketsuken.or.jp

KP-1461(replication inhibitor)

Koronis PharmaceuticalsRedmond, WA


lamivudine (3TC)/lopinavir/ ritonavir fixed-dose combination

Abbott LaboratoriesAbbott Park, IL

HIV-1 infection treatment in clinical trials(847) 937-6100

lamivudine (3TC)/maraviroc/zidovudine fixed-dose combination

GlaxoSmithKlineRsch. Triangle Park, NC

HIV infection Phase I completed(888) 825-5249

lersivirine (UK-453061)(NNRTI)

ViiV HealthcareRsch. Triangle Park, NC


Lexiva®

fosamprenavir(PI)

Vertex PharmaceuticalsCambridge, MAViiV HealthcareRsch. Triangle Park, NC

HIV infection treatment in adolescents, children and infants

Phase II(617) 444-6100(877) 844-8872


AntIVIrAlS


MK-1439(NNRTI)

MerckWhitehouse Station, NJ

HIV-1 infection treatment Phase I(800) 672-6273

Norvir®

ritonavirpowdered formulation(PI)

Abbott LaboratoriesAbbott Park, IL


NRT inhibitor Bristol-Myers SquibbPrinceton, NJ


prezista®

darunavir(once-daily 800 mg)


HIV infection application submitted(800) 526-7736

PRO 140(CCR5 receptor antagonist)

CytoDynLake Oswego, OR

HIV-1 infection prevention and treatment

Phase II completed(971) 204-0382

RAP101(CCR5 receptor antagonist)

RAPID PharmaceuticalsHuenenberg, Switzerland

HIV infection treatment Phase IIwww.rapidpharma.com

RPI-MN ReceptoPharmPlantation, FL

HIV infection treatment Phase I(954) 321-8988

S/GSK1265744(integrase inhibitor)

ShionogiFlorham Park, NJViiV HealthcareRsch. Triangle Park, NC

HIV infection treatment Phase II(973) 966-6900(877) 844-8872

SPL-7013(vaginal gel)

StarpharmaMelbourne, Australia

HIV infection prevention (Fast Track)

Phase I completedwww.starpharma.com

TBR-220(CCR5 receptor antagonist)

Tobira TherapeuticsSouth San Francisco, CA


tenofovir vaginal gel(NtRTI)

CONRADArlington, VAInternational Partnership for MicrobicidesSilver Spring, MD

HIV infection prevention Phase I(703) 524-4744

TMC310911(PI)


HIV infection treatment Phase II completed(800) 526-7736




AntIVIrAlS


UB-421(FI)

United BiomedicalHauppauge, NY


VRX806(NNRTI)

Valeant PharmaceuticalsMississauga, Canada


Cell tHerApy/Gene tHerApy


HIV gene therapy AdaptimmunePhiladelphia, PACardiff UniversityCardiff, WalesUniversity of PennsylvaniaPhiladelphia, PA

HIV infection Phase I(267) 499-2066

lexgenleucel-T(replication inhibitor)

VIRxSYSGaithersburg, MD

HIV infection therapy in treatment-experienced patients

Phase II(301) 987-0480

SB-728-T Sangamo BioSciencesRichmond, CA


Stealth Vector® HGTV-43™antisense gene medicine

Enzo TherapeuticsNew York, NY

HIV-1 infection treatment Phase I/II(212) 583-0100

ImmunomoDulAtorS


AMZ0026 Amazon BiotechNew York, NY

HIV infection treatment Phase I/II(212) 444-1019

CYT107(recombinant human interleukin-7)

CytherisRockville, MD


Cytolin®

anti-CD8 mAbCytoDynLake Oswego, OR


IRT-103(low-dose naltrexone)

TNI BioTechNew York, NY

HIV infection treatment Phase IIwww.tnibiotech.com



VACCIneS


ADVAX(DNA vaccine)

Aaron Diamond AIDS ResearchCenterNew York, NYInternational AIDS Vaccine InitiativeNew York, NYIchor Medical SystemsSan Diego, CA

HIV infection prevention

--------------------------------------------------HIV infection prevention(new delivery system)

Phase I completed(212) 448-5000(212) 847-1111-------------------------------------------Phase I completed(212) 448-5000(212) 847-1111

AGS-004(autologous dendritic cellvaccine-intradermal injection)

Argos TherapeuticsDurham, NC


AVX101(single gene HIV vaccine)

AlphaVaxRsch. Triangle Park, NC

HIV-1 infection prevention Phase I(919) 595-0400

DCVax-001(recombinant protein vaccine)

Celldex TherapeuticsNeedham, MARockefeller UniversityNew York, NY

HIV infection prevention and treatment

Phase I(781) 433-0771

DermaVir™ patchDNA topical patch vaccine

Genetic ImmunityMcLean, VA


HIV gp41 vaccine MymeticsEpalinges, Switzerland

HIV infection prevention Phase Iwww.mymetics.com

HIV recombinant vaccine GlaxoSmithKlineRsch. Triangle Park, NC


HIV vaccine CrucellLeiden, The NetherlandsBeth Israel Deaconess Medical CenterBoston, MAInternational AIDS Vaccine InitiativeNew York, NY


HIV vaccine GeoVax LabsSmyrna, GA

HIV infection prevention Phase II(678) 384-7220

HIV vaccine GeoVax LabsSmyrna, GA

HIV infection treatment Phase I/II(678) 384-7220



VACCIneS


HIV vaccine Massachusetts General HospitalBoston, MAOpal TherapeuticsParkville, Australia


HIV vaccine Novartis Vaccines & DiagnosticsCambridge, MANational Institutes of HealthBethesda, MD


HIV vaccine PaxVaxSan Diego, CA

HIV infection prevention in clinical trials(858) 450-9595

HIV vaccine(MAG pDNA)

Profectus BiosciencesBaltimore, MD


HIV vaccine(rVSV)

Profectus BiosciencesBaltimore, MD


HIV vaccine(SAV001)

SumagenSeoul, South Korea

HIV-1 infection Phase Iwww.sumagen.co.kr

HIVAX™replication-defective HIV-1 vaccine

GeneCure BiotechnologiesNorcross, GA

HIV-1 infection Phase I(770) 263-7508

ITV-1 immune therapeutic vaccine

Immunotech LaboratoriesPasadena, CA


pennvax®-BDNA vaccine (clade B)

Inovio PharmaceuticalsBlue Bell, PA

HIV infection prevention and treatment

Phase I(267) 440-4200

pennvax®-GDNA vaccine (clades A, C, D)

Inovio PharmaceuticalsBlue Bell, PA


TUTI-16(lipoprotein vaccine)

ThymonShort Hills, NJ

HIV-1 infection treatment Phase I/II(973) 467-9558

vacc-4x(intradermal vaccine)

Bionor PharmaOslo, Norway

HIV-1 infection treatment Phase IIwww.bionorpharma.com


VACCIneS


VRC-HIVADV014-00-VP(HIV-1 recombinant adenovirusvaccine)

GenVecGaithersburg, MDVaccine Research Center (NIAID)Bethesda, MD

HIV infection prevention Phase II completedwww.vrc.nih.gov

VRC-HIVADV027-00-VP(HIV adenovector Ad35 vaccine)

GenVecGaithersburg, MDVaccine Research Center (NIAID)Bethesda, MD

HIV infection prevention Phase Iwww.vrc.nih.gov

VRC-HIVDNA016-00-VP Vaccine Research Center (NIAID)Bethesda, MD

HIV infection prevention Phase IIwww.vrc.nih.gov


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 16, 2012. The information in this report may not be comprehensive. For more specific informa-tion about a particular product, contact the individual company directly or go to www.clinicaltrials.gov. The entire series of Medicines in Development is available on PhRMA’s web site.

A publication of phRMA’s Communications & public Affairs Department. (202) 835-3460

www.phrma.org | www.innovation.org | www.pparx.org | www.buysafedrugs.info

Provided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association.

Copyright © 2012 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given.

pharmaceutical Research and Manufacturers of America • 950 F Street, NW, Washington, DC 20004


Approved Medicines for HIV Infection/AIDS

entry Inhibitors

• Selzentry® (maraviroc) ViiV Healthcare

• Fuzeon® (enfuvirtide) Genentech, Trimeris

Integrase Inhibitor

• Isentress® (raltegravir) Merck

Nucleoside Reverse transcriptase Inhibitors (NRtI)

• Combivir® (lamivudine/zidovudine) ViiV Healthcare

• emtriva® (emtricitabine) Gilead Sciences

• epivir® (lamivudine) ViiV Healthcare

• epzicom® (abacavir/lamivudine) ViiV Healthcare

• Hivid® (zalcitabine) Roche, marketing discontinued

• Retrovir® (zidovudine) ViiV Healthcare

• trizivir® (abacavir/lamivudine/zidovudine) ViiV Healthcare

• Videx® (didanosine) Bristol-Myers Squibb

• Videx® EC (didanosine delayed release) Bristol-Myers Squibb

• Zerit® (stavudine) Bristol-Myers Squibb

• Zerit® XR (stavudine extended-release) Bristol-Myers Squibb, marketing discontinued

• Ziagen® (abacavir) ViiV Healthcare

Non-Nucleoside Reverse transcriptase Inhibitors (NNRtI)

• edurant™ (rilpivirine) Janssen Therapeutics

• Intelence® (etravirine) Janssen Therapeutics

• Rescriptor® (delvaridine) ViiV Healthcare

• Sustiva® (efavirenz) Bristol-Myers Squibb

• Viramune® (nevirapine) Boehringer Ingelheim Pharmaceuticals

• Viramune®XR™ (nevirapine extended-release) Boehringer Ingelheim Pharmaceuticals


Nucleotide Reverse transcriptase Inhibitor (NtRtI)

• Viread® (tenofovir disoproxil fumarate) Gilead Sciences

protease Inhibitors

• Agenerase® (amprenavir) GlaxoSmithKline, Vertex Pharmaceuticals

• Aptivus® (tipranavir) Boehringer Ingelheim Pharmaceuticals

• Crixivan® (indinavir) Merck

• Fortovase® (saquinavir soft-gel) Roche, marketing discontinued

• Invirase® (saquinavir) Genentech

• Kaletra® (lopinavir/ritonavir) Abbott Laboratories

• Lexiva® (fosamprenavir) ViiV Healthcare, Vertex Pharmaceuticals

• Norvir® (ritonavir) Abbott Laboratories

• prezista® (darunavir) Janssen Therapeutics

• Reyataz® (atazanavir) Bristol-Myers Squibb

• Viracept® (nelfinavir) ViiV Healthcare

Combination Medicines

NNRTI/NRTI/NtRTI

• Atripla® (efavirenz/emtricitabine/tenofovir disoproxil fumarate) Bristol-Myers Squibb, Gilead Sciences

NRTI/NNRTI/NtRTI

• Complera™ (emtricitabine/rilpivirine/tenofovir, disoproxil fumarate) Gilead Sciences

Integrase Inhibitor/PK Enhancer/NRTI/NtRTI

• Stribild™ (elvitegravor/cobicistat/emtricitabine/tenofvoir disoproxil fumarate) Gilead Sciences

NRTI/NtRTI

• truvada® (emtricitabine/tenofovir disoproxil fumarate) Gilead Sciences

Approved Medicines for HIV Infection/AIDS


Glossary

application submitted—An application for marketing has been submitted by the company to the Food and Drug Administration (FDA).

entry inhibitor—Unlike other HIV drugs that work after HIV has entered the human immune cell, entry inhibitors work outside the CD4 cell, blocking the virus from entering the cell. The process of HIV entry into a cell requires a series of steps in sequence involving several key proteins. Different entry inhibitors target separate proteins in the process. One type of entry inhibitor blocks the attachment of the HIV protein gp120 to CD4 cell receptors on the cell surface. Another inhibitor targets the binding of the virus to CCR5 or CXCR4 co-receptors involved in the virus entering the cell. And a third entry inhibitor interferes with the fusion of the HIV virus with T-cells at the cell membrane.

HIV infection—The presence of antibodies in the blood to the human immunodeficiency virus (the virus that causes AIDS). HIV-1 refers to the most common strain of the virus found in U.S. AIDS patients.

integrase inhibitor— A class of antiretroviral drugs designed to block the action of integrase, an enzyme that inserts the virus into the DNA of human cells. Since integration is a vital step

in the virus’ replication, blocking it can halt further spread of the virus.

pK enhancer—Pharmacokinetic (PK) en-hancer increases the effectiveness of pharma-ceutical treatment.

reverse transcriptase inhibitor (RtI)—When HIV infects a cell, reverse transcriptase changes the single-stranded RNA into a double-stranded viral DNA. The new viral DNA is then integrated into the human DNA cells, al-lowing reproduction of the virus. RTIs block this action and prevent completion of synthesis of the double-stranded viral DNA, preventing HIV from multiplying. RTIs are a class of antiretro-viral drugs.

NRtI—Nucleoside reverse transcriptase inhibitor.

NNRtI—Non-nucleoside reverse transcriptase inhibitor.

NtRtI—Nucleotide reverse transcriptase inhibitor.

phase 0—First-in-human trials conducted in accordance with FDA’s 2006 guidance on exploratory Investigational New Drug (IND) studies designed to speed up development of

promising drugs by establishing very early on whether the agent behaves in human subjects as was anticipated from preclinical studies.

phase I—Researchers test the drug in a small group of people, usually between 20 and 80 healthy adult volunteers, to evaluate its initial safety and tolerability profile, determine a safe dosage range, and identify potential side effects.

phase II—The drug is given to volunteer patients, usually between 100 and 300, to see if it is effective, identify an optimal dose, and to further evaluate its short-term safety.

phase III—The drug is given to a larger, more diverse patient population, often involving be-tween 1,000 and 3,000 patients (but sometime many more thousands), to generate statistically significant evidence to confirm its safety and effectiveness. They are the longest studies, and usually take place in multiple sites around the world.

pI—Protease inhibitors are a class of antiret-roviral drugs used to treat HIV infection. They prevent the HIV virus from replicating by inhib-iting the activity of proteases, such as HIV-1.


Selected Facts about HIV/AIDS

• In 2010, 2.7 million people became newly infected with HIV infection (including 390,000 children younger than age 15), down from 3.1 million in 2001. Although the annual number of people newly infected with HIV has dropped since its peak in the late 1990s, it is still occur-ring at an unacceptably high rate: between 2.5 million and 3 million people annually for the past five years, adding to the global number of people living with HIV that reached 34 million (including 3.4 million children younger than age 15) by the end of 2010.

• Globally, the annual number of people newly infected with HIV continues to decline, although there is stark regional variation. In sub-Saharan Africa, where most of the people newly infected with HIV live, an estimated 1.9 million people became infected in 2010. That was 16 percent fewer than the estimated 2.2 million people newly infected with HIV in 2001, and 27 percent fewer than the annual number of people newly infected between 1996 and 1998, when the incidence of HIV in sub-Saharan Africa peaked overall.

• Reductions in the number of people acquiring HIV infection, especially people ages 15–24 in the countries in sub-Saharan Africa that have a high burden of HIV, have been offset by increases in new infections in eastern europe and Central Asia. In those areas, where the primary mode of transmission of HIV is among people who inject drugs and their sexual networks, the number of people dying from AIDS-related causes increased 1,100 percent during the past decade: from an estimated 7,800 in 2001 to 89,500 in 2010.

• The annual number of people dying from AIDS-related causes worldwide is steadily decreasing from a peak of 2.2 million in 2005 to an estimated 1.8 million in 2010. That year, an estimated 250,000 children younger than age 15 died from AIDS-related causes, 20 percent fewer than in 2005. The number of people dying from AIDS-related causes began to decline in 2005–2006 in sub-Saharan Africa, South and Southeast Asia and the Caribbean and has continued subsequently.

• Introducing antiretroviral therapy has averted 2.5 million AIDS deaths in low- and middle-income countries globally since 1995. Sub-Saharan Africa accounts for the vast majority of the averted deaths: about 1.8 million.

• Providing antiretroviral prophylaxis to pregnant women living with HIV has prevented more than 350,000 children from acquiring HIV infection since 1995. Eighty-six percent of the children who avoided infection live in sub-Saharan Africa, the region with the highest prevalence of HIV infection among women of reproductive age.

overview

HIV/AIDS Worldwide 2

U.S. AIDS Diagnoses through 20101 U.S. AIDS Deaths through 20091

Adults/Adolescents 1,119,651 614,394

Pediatric (under age 13) 9,475 4,986

totAL 1,163,575* 641,976*

* Because totals for the estimated numbers were calculated independently of the values for the subpopulations, the subpopulation values may not equal these totals.


Selected Facts about HIV/AIDS

HIV/AIDS in the United States1

• In 2010, an estimated 48,298 people were newly diagnosed with HIV infection in the 46 states and 5 U.S. dependent areas with confidential name-based HIV infection reporting. In the 46 states, 46,912 adults and adolescents were newly diagnosed with HIV infection, with 37,045 diag-noses in males and 9,868 diagnoses in females. Among children younger than age 13, there were an estimated 217 diagnoses of HIV infection.

• At the end of 2009, an estimated 1,148,200 people age 13 and older were living with HIV infection in the United States, including 207,600 people whose infections had not been diagnosed.

• In 2009, the estimated number of deaths of people with a diagnosis of HIV infection in the 46 states and 5 U.S. dependent areas with confidential name-based HIV infection reporting was 21,601. In the 46 states only, that included 21,007 adults and adolescents and 8 children younger than age 13.

• In 2010, the estimated number of people diagnosed with AIDS in the United States and 6 U.S. dependent areas was 33,630. In the 50 states and the District of Columbia, 24,749 AIDS diagnoses were among adult and adolescent males, 8,242 were among adult and adolescent females, and 23 diagnoses were among children younger than age 13.

• In 2009, the estimated number of deaths of people with an AIDS diagnosis in the United States and 6 U.S. dependent areas was 18,234. In the 50 states and the District of Columbia, that included 17,770 adults and adolescents and 4 children younger than age 13.

HIV/AIDS economic Impact

• The lifetime treatment cost of an HIV infection can be used as a conservative threshold value for the cost of averting one infection. Currently, the lifetime treatment cost of an HIV infection is estimated at $379,668 (in 2010 dollars); therefore, a prevention intervention is deemed cost-saving if its cost-effectiveness (CE) ratio is less than $379,668 per infection averted. The average annual cost of HIV care in the antiretroviral (ART) era is estimated to be $19,912 (in 2006 dollars; $23,000 in 2010 dollars). One study has estimated the medical savings from infections averted by United States prevention programs from 1991-2006 to be $129.9 billion with 361,878 HIV infections averted.1

• Nearly 30 years into the HIV epidemic, HIV continues to take a heavy toll in the United States. More than 1.1 million people are currently living with HIV, nearly 18,000 people with AIDS still die each year, and lifetime medical care for those who become infected with HIV each year is estimated to cost $20 billion.1

• Without intervention, a perinatal HIV transmission rate of 25 percent would result in 1,750 HIV-infected infants born annually in the United States with lifetime medical costs estimated to be $282 million. The cost of intervention (HIV counseling, testing, and zidovu-dine treatment) was estimated to be $67.6 million. That intervention would prevent 656 pediatric HIV infections, saving $105.6 million in medical care costs—a net cost-savings of $38.1 million annually.3

Sources:

1. U.S. Centers for Disease Control and Prevention, HIV Surveillance Report: Diagnoses of HIV Infection and AIDS in the United States and Dependent Areas, 2010; Vol. 22., www.cdc.gov

2. World Health Organization (WHO), www.who.int/en

3. KidSource OnLine, Inc., www.kidsource.com

The Drug Discovery, Development and Approval Process

the U.S. system of new drug approvals is perhaps the most rigorous in the world.It takes 10-15 years, on average, for an experimental drug to travel from lab to U.S. patients, according to the Tufts Center for the Study of Drug Development. Only five in 5,000 compounds that enter preclinical testing make it to human testing. And only one of those five is approved for sale.On average, it costs a company $1.2 billion, including the cost of failures, to get one new medicine from the laboratory to U.S. patients, according to a 2007 study by the Tufts Center for the Study of Drug Development.Once a new compound has been identified in the laboratory, medicines are usually devel-oped as follows:preclinical testing. A pharmaceutical com-pany conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the com-pound is evaluated for safety.Investigational New Drug Application (IND). After completing preclinical testing, a company files an IND with the U.S. Food and Drug Administration (FDA) to begin to test the drug

in people. The IND shows results of previous experiments; how, where and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in the animal studies; and how the compound is manufactured. All clinical trials must be reviewed and approved by the Institutional Review Board (IRB) where the trials will be conducted. Progress reports on clinical trials must be submitted at least annually to FDA and the IRB.Clinical trials, phase I—Researchers test the drug in a small group of people, usually between 20 and 80 healthy adult volunteers, to evaluate its initial safety and tolerability profile, determine a safe dosage range, and identify potential side effects.Clinical trials, phase II—The drug is given to volunteer patients, usually between 100 and 300, to see if it iseffective, identify an optimal dose, and to further evaluate its short-term safety.Clinical trials, phase III—The drug is given to a larger, more diverse patient population, often involving between 1,000 and 3,000 patients (but sometime many more thousands), to generate

statistically significant evidence to confirm its safety and effectiveness. They are the longest studies, and usually take place in multiple sites around the world.New Drug Application (NDA)/Biologic License Application (BLA). Following the completion of all three phases of clinical trials, a company analyzes all of the data and files an NDA or BLA with FDA if the data successfully demonstrate both safety and effectiveness. The applications contain all of the scientific information that the company has gathered. Applications typically run 100,000 pages or more.Approval. Once FDA approves an NDA or BLA, the new medicine becomes available for physicians to prescribe. A company must continue to submit periodic reports to FDA, including any cases of adverse reactions and appropriate quality-control records. For some medicines, FDA requires additional trials (Phase IV) to evaluate long-term effects. Discovering and developing safe and effective new medicines is a long, difficult, and expensive process. PhRMA member companies invested an estimated $49.5 billion in research and development in 2011.

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.

The Drug Development and Approval Process

PhRMA Report 2012: Medicines in Development for HIV/AIDS

Health & Medicine

Transcript of PhRMA Report 2012: Medicines in Development for HIV/AIDS