VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
PhRMA Report 2012: Medicines in Development for HIV/AIDS
1. 2012 Report
Medicines in Development
HIV/AIDS
presented by america’s biopharmaceutical
research companies
Biopharmaceutical Researchers Are Testing
More Than 70 Medicines and Vaccines For
HIV Infection
Medicines in Development
for HIV/AIDS
40
1.2 million Americans
25 are living with HIV,
50,000 are newly diagnosed
each year
4 4
Biopharmaceutical research companies vaccine given to only a third of the population
ls
s
py
es
or
ira
are developing 73 medicines and vaccines, could reduce new HIV infections by 24 percent
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focusing on improved treatment regimens, over 15 years.
An
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eT
mo
more effective therapies and promising new
en
no
The medicines in the development pipeline
ll/G
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preventative vaccines.
include:
Ce
Im
Although HIV/AIDS is one of the most
• gene therapy that uses genetic material to
A
Medicines in Development devastating diseases affecting people around
for HIV/AIDS by Phase of remove disease-causing aspects of the virus.
the world, the number of new infections has
Development been steadily declining. In the United States, • transdermal vaccine that helps suppress vi-
A
the AIDS-related death rate has fallen by 79 rus replication and destroys HIV-infected cells.
35
percent due to antiretroviral therapy. • first-in-class medicine intended to prevent the
A
28
Over the past 30 years, nearly 40 medicines HIV virus from breaking through the cell membrane.
have been approved to treat HIV/AIDS. Despite the incredible progress to date, the
Testing for the disease also has advanced HIV/AIDS epidemic remains a complex prob-
dramatically, enabling earlier treatment. While lem. America’s biopharmaceutical research
2
5 4 these medicines have helped to prolong the companies are continuing their efforts to de-
lives of HIV-infected patients, making HIV a velop novel and more effective therapies, vac-
manageable chronic disease, opportunities for cines to prevent the disease, and potentially a
eI
II
I
d
itte n
eI
eI
d
ifie
even greater progress remain.
bm tio
as
cure, so the millions of patients suffering today
as
as
Su lica
ec
Ph
Ph
Ph
sp
For example, biopharmaceutical companies have hope for a better tomorrow.
p
Ap
Un
are intensifying their efforts to develop vac-
* Some medicines are listed in more than one cines that would help prevent HIV. Current
phase of development. estimates show that a 50 percent effective
2. Medicines in Development for HIV/AIDS
Antivirals
Product Name Sponsor Indication Development Status*
abacavir/dolutegravir/lamivudine ViiV Healthcare HIV infection therapy in Phase III
fixed-dose combination Rsch. Triangle Park, NC treatment-naive patients (877) 844-8872
(integrase inhibitor/reverse
transcriptase inhibitor)
amdoxovir (DAPD) RFS Pharma HIV-1 infection treatment Phase II
Tucker, GA (404) 601-1430
BI-224436 Gilead Sciences HIV infection treatment Phase I completed
(integrase inhibitor) Foster City, CA (800) 445-3235
CB1922 Canopus BioPharma HIV infection treatment Phase II
(synthetic steroidal lactone) Studio City, CA www.canopusbiopharma.com
cenicriviroc Tobira Therapeutics HIV-1 infection treatment Phase II
(CCR5 receptor antagonist) South San Francisco, CA (650) 741-6625
CMX157 Merck HIV infection treatment Phase I completed
(tenofovir PIM conjugate) Whitehouse Station, NJ (800) 672-6372
cobicistat Gilead Sciences HIV infection treatment application submitted
(PK enhancer) Foster City, CA (800) 445-3235
cobicistat/darunavir Gilead Sciences HIV infection Phase I
fixed-dose combination Foster City, CA (800) 445-3235
(PK enhancer/protease Janssen Therapeutics (800) 526-7736
inhibitor)
Titusville, NJ
cobicistat/darunavir/ Gilead Sciences HIV-1 infection Phase II
emtricitabine/GS-7340 Foster City, CA (800) 445-3235
fixed-dose combination Janssen Therapeutics (800) 526-7736
Titusville, NJ
cobicistat/elvitegravir/ Gilead Sciences HIV-1 infection Phase II
emtricitabine/GS-7340 Foster City, CA (800) 445-3235
fixed-dose combination
dapivirine International Partnership for HIV infection prevention Phase I/II completed
(NNRTI) Microbicides (vaginal ring) (301) 608-2221
Silver Spring, MD -------------------------------------------------- -------------------------------------------
HIV infection prevention Phase I/II completed
(vaginal gel) (301) 608-2221
dolutegravir Shionogi HIV-1 infection treatment Phase III
(S/GSK1349572) Florham Park, NJ (973) 966-6900
(integrase inhibitor) ViiV Healthcare (877) 844-8872
Rsch. Triangle Park, NC
*For more information about a specific medicine in this report, please call the telephone number listed.
2 Medicines in Development HIV/AIDS 2012
3. Medicines in Development for HIV/AIDS
Antivirals
Product Name Sponsor Indication Development Status
efavirenz/lamivudine/ Mylan Laboratories HIV-1 infection treatment application submitted
tenofovir fumarate Canonsburg, PA (724) 514-1800
fixed-dose combination
elvitegravir Gilead Sciences HIV-1 infection treatment application submitted
(integrase inhibitor) Foster City, CA (800) 445-3235
elvucitabine Achillion Pharmaceuticals HIV infection treatment Phase II
(NRTI) New Haven, CT (203) 624-7000
GS-7340 Gilead Sciences HIV infection treatment Phase II
(NtRTI) Foster City, CA (800) 445-3235
HIV attachment inhibitor Bristol-Myers Squibb HIV infection treatment Phase II
Princeton, NJ (800) 332-2056
HIV maturation inhibitor Bristol-Myers Squibb HIV infection treatment in clinical trials
Princeton, NJ (800) 332-2056
ibalizumab TaiMed Biologics USA HIV-1 infection treatment Phase II
(TMB-355) Irvine, CA (intravenous) (Fast Track) (949) 769-6543
(fusion inhibitor) -------------------------------------------------- -------------------------------------------
HIV-1 infection treatment Phase I
(subcutaneous) (949) 769-6543
Intelence® Janssen Therapeutics HIV infection combination therapy in Phase II
etravirine Titusville, NJ treatment-naive patients (800) 526-7736
(NNRTI) (Fast Track)
KD-247 Kaketsuken HIV-1 infection treatment Phase I
(monoclonal antibody) Kumamoto, Japan www.kaketsuken.or.jp
KP-1461 Koronis Pharmaceuticals HIV infection treatment Phase II
(replication inhibitor) Redmond, WA (425) 825-0240
lamivudine (3TC)/lopinavir/ Abbott Laboratories HIV-1 infection treatment in clinical trials
ritonavir fixed-dose Abbott Park, IL (847) 937-6100
combination
lamivudine (3TC)/maraviroc/ GlaxoSmithKline HIV infection Phase I completed
zidovudine fixed-dose Rsch. Triangle Park, NC (888) 825-5249
combination
lersivirine (UK-453061) ViiV Healthcare HIV infection treatment Phase II
(NNRTI) Rsch. Triangle Park, NC (877) 844-8872
Lexiva® Vertex Pharmaceuticals HIV infection treatment in Phase II
fosamprenavir Cambridge, MA adolescents, children and infants (617) 444-6100
(PI) ViiV Healthcare (877) 844-8872
Rsch. Triangle Park, NC
Medicines in Development HIV/AIDS 2012 3
4. Medicines in Development for HIV/AIDS
Antivirals
Product Name Sponsor Indication Development Status
MK-1439 Merck HIV-1 infection treatment Phase I
(NNRTI) Whitehouse Station, NJ (800) 672-6273
Norvir® Abbott Laboratories HIV infection treatment in clinical trials
ritonavir Abbott Park, IL (847) 937-6100
powdered formulation
(PI)
NRT inhibitor Bristol-Myers Squibb HIV infection treatment Phase II
Princeton, NJ (800) 332-2056
Prezista® Janssen Therapeutics HIV infection application submitted
darunavir Titusville, NJ (800) 526-7736
(once-daily 800 mg)
PRO 140 CytoDyn HIV-1 infection prevention and Phase II completed
(CCR5 receptor antagonist) Lake Oswego, OR treatment (971) 204-0382
RAP101 RAPID Pharmaceuticals HIV infection treatment Phase II
(CCR5 receptor antagonist) Huenenberg, Switzerland www.rapidpharma.com
RPI-MN ReceptoPharm HIV infection treatment Phase I
Plantation, FL (954) 321-8988
S/GSK1265744 Shionogi HIV infection treatment Phase II
(integrase inhibitor) Florham Park, NJ (973) 966-6900
ViiV Healthcare (877) 844-8872
Rsch. Triangle Park, NC
SPL-7013 Starpharma HIV infection prevention Phase I completed
(vaginal gel) Melbourne, Australia (Fast Track) www.starpharma.com
TBR-220 Tobira Therapeutics HIV infection treatment Phase I
(CCR5 receptor antagonist) South San Francisco, CA (650) 741-6625
tenofovir vaginal gel CONRAD HIV infection prevention Phase I
(NtRTI) Arlington, VA (703) 524-4744
International Partnership for
Microbicides
Silver Spring, MD
TMC310911 Janssen Therapeutics HIV infection treatment Phase II completed
(PI) Titusville, NJ (800) 526-7736
4 Medicines in Development HIV/AIDS 2012
5. Medicines in Development for HIV/AIDS
Antivirals
Product Name Sponsor Indication Development Status
UB-421 United Biomedical HIV-1 infection treatment Phase II
(FI) Hauppauge, NY (631) 273-2828
VRX806 Valeant Pharmaceuticals HIV infection treatment Phase II
(NNRTI) Mississauga, Canada (905) 286-3000
Cell Therapy/Gene Therapy
Product Name Sponsor Indication Development Status
HIV gene therapy Adaptimmune HIV infection Phase I
Philadelphia, PA (267) 499-2066
Cardiff University
Cardiff, Wales
University of Pennsylvania
Philadelphia, PA
lexgenleucel-T VIRxSYS HIV infection therapy in Phase II
(replication inhibitor) Gaithersburg, MD treatment-experienced patients (301) 987-0480
SB-728-T Sangamo BioSciences HIV infection treatment Phase II
Richmond, CA (510) 970-6000
Stealth Vector® Enzo Therapeutics HIV-1 infection treatment Phase I/II
HGTV-43™ New York, NY (212) 583-0100
antisense gene medicine
Immunomodulators
Product Name Sponsor Indication Development Status
AMZ0026 Amazon Biotech HIV infection treatment Phase I/II
New York, NY (212) 444-1019
CYT107 Cytheris HIV infection treatment Phase II
(recombinant human Rockville, MD (301) 231-0450
interleukin-7)
Cytolin® CytoDyn HIV infection treatment Phase I
anti-CD8 mAb Lake Oswego, OR (971) 204-0382
IRT-103 TNI BioTech HIV infection treatment Phase II
(low-dose naltrexone) New York, NY www.tnibiotech.com
Medicines in Development HIV/AIDS 2012 5
6. Medicines in Development for HIV/AIDS
Vaccines
Product Name Sponsor Indication Development Status
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
AGS-004 Argos Therapeutics HIV-1 infection treatment Phase II
(autologous dendritic cell Durham, NC (919) 287-6300
vaccine-intradermal injection)
AVX101 AlphaVax HIV-1 infection prevention Phase I
(single gene HIV vaccine) Rsch. Triangle Park, NC (919) 595-0400
DCVax-001 Celldex Therapeutics HIV infection prevention and Phase I
(recombinant protein vaccine) Needham, MA treatment (781) 433-0771
Rockefeller University
New York, NY
DermaVir™ Patch Genetic Immunity HIV-1 infection treatment Phase II
DNA topical patch vaccine McLean, VA (703) 879-6803
HIV gp41 vaccine Mymetics HIV infection prevention Phase I
Epalinges, Switzerland www.mymetics.com
HIV recombinant vaccine GlaxoSmithKline HIV-1 infection prevention Phase I
Rsch. Triangle Park, NC (888) 825-5249
HIV vaccine Crucell HIV infection prevention Phase I
Leiden, The Netherlands (212) 847-1111
Beth Israel Deaconess Medical
Center
Boston, MA
International AIDS Vaccine Initiative
New York, NY
HIV vaccine GeoVax Labs HIV infection prevention Phase II
Smyrna, GA (678) 384-7220
HIV vaccine GeoVax Labs HIV infection treatment Phase I/II
Smyrna, GA (678) 384-7220
6 Medicines in Development HIV/AIDS 2012
7. Medicines in Development for HIV/AIDS
Vaccines
Product Name Sponsor Indication Development Status
HIV vaccine Massachusetts General Hospital HIV infection Phase I
Boston, MA (617) 726-2000
Opal Therapeutics
Parkville, Australia
HIV vaccine Novartis Vaccines Diagnostics HIV infection Phase I
Cambridge, MA (617) 871-7000
National Institutes of Health
Bethesda, MD
HIV vaccine PaxVax HIV infection prevention in clinical trials
San Diego, CA (858) 450-9595
HIV vaccine Profectus Biosciences HIV-2 infection prevention Phase I
(MAG pDNA) Baltimore, MD (866) 938-8559
HIV vaccine Profectus Biosciences HIV infection prevention Phase I
(rVSV) Baltimore, MD (866) 938-8559
HIV vaccine Sumagen HIV-1 infection Phase I
(SAV001) Seoul, South Korea www.sumagen.co.kr
HIVAX™ GeneCure Biotechnologies HIV-1 infection Phase I
replication-defective Norcross, GA (770) 263-7508
HIV-1 vaccine
ITV-1 Immunotech Laboratories HIV infection treatment in clinical trials
immune therapeutic vaccine Pasadena, CA (818) 409-9091
Pennvax®-B Inovio Pharmaceuticals HIV infection prevention and Phase I
DNA vaccine (clade B) Blue Bell, PA treatment (267) 440-4200
Pennvax®-G Inovio Pharmaceuticals HIV infection prevention Phase I
DNA vaccine (clades A, C, D) Blue Bell, PA (267) 440-4200
TUTI-16 Thymon HIV-1 infection treatment Phase I/II
(lipoprotein vaccine) Short Hills, NJ (973) 467-9558
vacc-4x Bionor Pharma HIV-1 infection treatment Phase II
(intradermal vaccine) Oslo, Norway www.bionorpharma.com
Medicines in Development HIV/AIDS 2012 7
11. Glossary
application submitted—An application for in the virus’ replication, blocking it can halt promising drugs by establishing very early on
marketing has been submitted by the company further spread of the virus. whether the agent behaves in human subjects
to the Food and Drug Administration (FDA). as was anticipated from preclinical studies.
PK enhancer—Pharmacokinetic (PK) en-
entry inhibitor—Unlike other HIV drugs that hancer increases the effectiveness of pharma- Phase I—Researchers test the drug in a small
work after HIV has entered the human immune ceutical treatment. group of people, usually between 20 and 80
cell, entry inhibitors work outside the CD4 healthy adult volunteers, to evaluate its initial
reverse transcriptase inhibitor (RTI)—When
cell, blocking the virus from entering the cell. safety and tolerability profile, determine a
HIV infects a cell, reverse transcriptase
The process of HIV entry into a cell requires a safe dosage range, and identify potential side
changes the single-stranded RNA into a
series of steps in sequence involving several effects.
double-stranded viral DNA. The new viral DNA
key proteins. Different entry inhibitors target
is then integrated into the human DNA cells, al- Phase II—The drug is given to volunteer
separate proteins in the process. One type of
lowing reproduction of the virus. RTIs block this patients, usually between 100 and 300, to see
entry inhibitor blocks the attachment of the HIV
action and prevent completion of synthesis of if it is effective, identify an optimal dose, and to
protein gp120 to CD4 cell receptors on the cell
the double-stranded viral DNA, preventing HIV further evaluate its short-term safety.
surface. Another inhibitor targets the binding
from multiplying. RTIs are a class of antiretro-
of the virus to CCR5 or CXCR4 co-receptors Phase III—The drug is given to a larger, more
viral drugs.
involved in the virus entering the cell. And a diverse patient population, often involving be-
third entry inhibitor interferes with the fusion of NRTI—Nucleoside reverse transcriptase tween 1,000 and 3,000 patients (but sometime
the HIV virus with T-cells at the cell membrane. inhibitor. many more thousands), to generate statistically
significant evidence to confirm its safety and
HIV infection—The presence of antibodies in NNRTI—Non-nucleoside reverse transcriptase effectiveness. They are the longest studies,
the blood to the human immunodeficiency virus inhibitor. and usually take place in multiple sites around
(the virus that causes AIDS). HIV-1 refers to
NtRTI—Nucleotide reverse transcriptase the world.
the most common strain of the virus found in
U.S. AIDS patients. inhibitor. PI—Protease inhibitors are a class of antiret-
Phase 0—First-in-human trials conducted roviral drugs used to treat HIV infection. They
integrase inhibitor— A class of antiretroviral
in accordance with FDA’s 2006 guidance on prevent the HIV virus from replicating by inhib-
drugs designed to block the action of integrase,
exploratory Investigational New Drug (IND) iting the activity of proteases, such as HIV-1.
an enzyme that inserts the virus into the DNA
of human cells. Since integration is a vital step studies designed to speed up development of
Medicines in Development HIV/AIDS 2012 11
12. Selected Facts about HIV/AIDS
Overview
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*
* ecause totals for the estimated numbers were calculated independently of the values for the subpopulations, the subpopulation values may not
B
equal these totals.
HIV/AIDS Worldwide 2
• 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.
12 Medicines in Development HIV/AIDS 2012
13. Selected Facts about HIV/AIDS
HIV/AIDS in the United States 1
• 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
Medicines in Development HIV/AIDS 2012 13
14. The Drug Discovery, Development and Approval Process
Developing a new medicine takes an average of 10-15 years;
For every 5,000-10,000 compounds in the pipeline, only 1 is approved.
The Drug Development and Approval Process
The U.S. system of new drug approvals is in people. The IND shows results of previous statistically significant evidence to confirm its
perhaps the most rigorous in the world. experiments; how, where and by whom the safety and effectiveness. They are the longest
new studies will be conducted; the chemical studies, and usually take place in multiple sites
It takes 10-15 years, on average, for an
structure of the compound; how it is thought around the world.
experimental drug to travel from lab to U.S.
to work in the body; any toxic effects found in
patients, according to the Tufts Center for the New Drug Application (NDA)/Biologic
the animal studies; and how the compound
Study of Drug Development. Only five in 5,000 License Application (BLA). Following the
is manufactured. All clinical trials must be
compounds that enter preclinical testing make completion of all three phases of clinical trials,
reviewed and approved by the Institutional
it to human testing. And only one of those five a company analyzes all of the data and files an
Review Board (IRB) where the trials will be
is approved for sale. NDA or BLA with FDA if the data successfully
conducted. Progress reports on clinical trials
demonstrate both safety and effectiveness.
On average, it costs a company $1.2 billion, must be submitted at least annually to FDA and
The applications contain all of the scientific
including the cost of failures, to get one new the IRB.
information that the company has gathered.
medicine from the laboratory to U.S. patients,
Clinical Trials, Phase I—Researchers test Applications typically run 100,000 pages or
according to a 2007 study by the Tufts Center
the drug in a small group of people, usually more.
for the Study of Drug Development.
between 20 and 80 healthy adult volunteers, to
Approval. Once FDA approves an NDA or
Once a new compound has been identified in evaluate its initial safety and tolerability profile,
BLA, the new medicine becomes available
the laboratory, medicines are usually devel- determine a safe dosage range, and identify
for physicians to prescribe. A company must
oped as follows: potential side effects.
continue to submit periodic reports to FDA,
Preclinical Testing. A pharmaceutical com- Clinical Trials, Phase II—The drug is given including any cases of adverse reactions and
pany conducts laboratory and animal studies to volunteer patients, usually between 100 and appropriate quality-control records. For some
to show biological activity of the compound 300, to see if it iseffective, identify an optimal medicines, FDA requires additional trials
against the targeted disease, and the com- dose, and to further evaluate its short-term (Phase IV) to evaluate long-term effects.
pound is evaluated for safety. safety.
Discovering and developing safe and effective
Investigational New Drug Application (IND). Clinical Trials, Phase III—The drug is given to new medicines is a long, difficult, and expensive
After completing preclinical testing, a company a larger, more diverse patient population, often process. PhRMA member companies invested
files an IND with the U.S. Food and Drug involving between 1,000 and 3,000 patients (but an estimated $49.5 billion in research and
Administration (FDA) to begin to test the drug sometime many more thousands), to generate development in 2011.
