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2014 REPORT

MEDICINES IN DEVELOPMENT FOR

Mental Health
PRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES

Biopharmaceutical Research Companies


Are Developing More Than 100 Medicines to
Treat Mental and Addictive Disorders
Mental health conditions exact a heavy dependent on developing a better un-
human and economic toll in the United derstanding of how current treatments
Medicines in Development States. The National Institute of Mental work, identifying biomarkers that can
For Mental Health Health (NIMH) estimates that 1 in 4 be used to improve diagnosis and as-
American adults—61.5 million—have been sess responses to therapies, and finding
Application diagnosed with a mental health disorder. new therapeutic targets through identifi-
Submitted
According to the NIMH, serious mental cation of the pathologies or mechanisms
Phase III illnesses cost the United States more than contributing to mental disorders.
Phase II $317 billion annually in lost wages, health
Examples of some medicines now being
care expenditures and disability benefits.
Phase I tested to treat specific mental disorders
Biopharmaceutical research companies include:
are currently developing 119 medicines
• A triple reuptake inhibitor that may
to help people who have some type of
provide a broader spectrum of thera-
mental disorder, such as anxiety, depres-
36 peutic activity for attention-deficit/
sion, schizophrenia, or substance use
hyperactivity disorder (ADHD).
disorders. Those medicines are either
29 in clinical trials or awaiting review by
the U.S. Food and Drug Administration Contents
(FDA), with more than 75 percent of Challenges in Mental Health
20 Research ......................................... 2
the medicines in the earliest phases
15 15 of research and development—a time Medicines in the Pipeline .................. 3
Collaborative Research
when potential treatments often face
Partnerships .................................... 5
difficult hurdles and setbacks.
6 Early Scientific Discoveries ................6

Over the past half century, biopharma- Facts About Mental Health in the
United States ..................................8
ceutical research has helped alleviate the
Medicines in Development Chart ...... 11
burden and improve the quality of life
e
tan renia
De tism

on

Glossary ....................................... 24
An D
ty

dic /
tiv
Ad Use
H

for many individuals living with a mental


xie

ssi
AD

Drug Development/
Au

h
pre

ce

disorder. But therapeutic advances are


p

Approval Process ........................... 28


o
hiz

needed for people not helped by current


bs
Sc
Su

treatments or for those who experience


negative side effects. Further research
Some medicines are listed in more than one
category. into new or improved treatments is
Key Issues

the brain; a lack of biomarkers that help clinicians’ diagnose


MENTAL HEALTH accurately, measure disease progression and assess treatment
response; and the complexity of mental disorders them-
selves. In fact, most medicines that are in use today for the
treatment of mental disorders have stemmed from and built
on compounds that were initially developed many years ago.

61.5 MILLION
AMERICANS
NIMH’s practical guidelines have documented the sometimes
limited benefits of current treatments and the need for a new
generation of mental health medicines.

Specific challenges associated with developing new treat-


1 in 4 ments for mental disorders include diagnosis based on
has a symptoms rather than underlying pathology. This can
make it difficult to ensure that the appropriate participants
MENTAL ILLNESS are included in a clinical trial. For some disorders, such as
schizophrenia or autism spectrum disorder (ASD), individu-
als meeting the diagnostic criteria, may in reality comprise
Source: National Institute of Mental Health (NIMH). several subgroups, each with different underlying pathologies
even though they have similar symptoms. Therefore, the
medication under study may be targeting the appropriate
• An intranasal medicine for treatment-resistant depres- mechanism or pathology in only a subset of the clinical trial
sion that targets a receptor in the brain resulting in a participants. Even if the medicine is effective in that portion
rapid onset of antidepressant effects. of participants, it may appear to be ineffective because statisti-
cal tests assess the entire group. A greater understanding of
• A medicine for schizophrenia that targets a known treat-
ment pathway but with potentially fewer negative side
effects than existing treatments.
MENTAL HEALTH
Researching and developing new medicines is a risky invest-
ment and lengthy process—only one in 5,000-10,000 tar-

MENTAL
gets are ever approved for patients. And although advances
in our understanding of mental disorders and how to treat
them have allowed America’s biopharmaceutical companies
and other partners in the collaborative ecosystem to con-
ILLNESSES
duct cutting-edge research, additional scientific research is
needed to reduce the destructive toll of these disorders and
allow more people to lead healthier, more productive lives.

Challenges in Mental
Health Research
COST THE
U.S. $317 BILLION ANNUALLY
in lost wages, health care and disability
Development of new and effective treatments for mental
disorders has been hindered by many factors, including a Source: NIMH.

limited understanding of how current treatments work in

2 Medicines in Development for Mental Health 2014


Key Issues

tiple mental disorders. Further research is needed to support


MENTAL HEALTH the research and development efforts of the biopharmaceuti-
cal industry.

Medicines in the Pipeline

MENTAL
Although research into mental disorders can be very diffi-
cult, there are some promising medicines in the pipeline that
are looking at new ways to treat many of these disorders.

DISORDERS Examples of some current research include:

are the leading cause of Attention-Deficit/Hyperactivity Disorder (ADHD)


U.S. DISABILITY A triple reuptake inhibitor that targets three chemical pathways
in brain—serotonin, norepinephrine and dopamine—is being
tested for the once-daily treatment of ADHD. By targeting all
three pathways at the same time, the compound may poten-
Source: NIMH.
tially provide a broad spectrum of activity. Because of its ability
to maintain therapeutic levels in the blood for a long period
of time, it is being developed as a once-daily treatment.
mental disorders will help with diagnosis accuracy and ensure
clinical trial participants are grouped appropriately. Cocaine Addiction
Currently, there are no medications that explicitly address
At NIMH, several initiatives are underway to help advance
cocaine addiction, but a therapeutic vaccine in develop-
research into potential new treatments for mental disor-
ders. One project is focused on creating a new framework
to classify mental disorders based on observable behavior
and neurobiological measures, such as biomarkers. Current MENTAL HEALTH
classifications are based on clinical observation and patient- MEDICINES IN DEVELOPMENT
reported symptoms. As scientists gain more knowledge of
the underlying biologic causes of mental disorders, having a
disorder classification framework ready will aid in a faster and
119 TOTAL Medicines

more accurate diagnosis, leading to real progress in research-


ing new treatments. 36
SCHIZOPHRENIA
for 15 for
ATTENTION-DEFICIT/
For example, several research collaborations are looking at HYPERACTIVITY DISORDER
the human genome to identify potential genetic indicators for
schizophrenia and understand the association between dif-
29
DEPRESSION
for 15 for
ANXIETY DISORDERS
ferent genetic factors and different subpopulations of people
diagnosed with the disorder. Such research could lead to the
identification of new targets more closely linked to disease
20
SUBSTANCE USE/
for 6 for
AUTISM SPECTRUM
pathology versus overall symptoms. In addition, the research ADDICTIVE DISORDERS DISORDERS
has highlighted how difficult it is to find specific markers or and more…
targets because some gene variants are associated with mul- Source: PhRMA 2014 Medicines in Development for Mental Health.

Medicines in Development for Mental Health 2014 3


Key Issues

MENTAL HEALTH Social Phobia


One medicine in development is part of a new class of
psychotropic pherines. The drug, which has a unique mecha-
nism of action, is being developed to be administered in an
intranasal spray and to act with rapid-onset on peripheral
receptors from nasal chemosensory neurons that act on the
hypothalamic-limbic system in the brain, which is thought
to be the primary center of emotion. In clinical trials, it was
shown to improve social performance and social interaction
anxiety within 10 minutes of administration.

ADHD Schizophrenia

1 in 20
Several medicines in development for schizophrenia are
AFFECTS inhibitors of a subtype of phosphodiesterase (PDE), a key

U.S. CHILDREN regulator of signaling in the brain. The PDE10 subtype is


important in regulating the activity of neurons in the brain
Source: Mental Health America.
and is a target of current antipsychotic treatments. PDE10
inhibitors are highly selective and mimic the effects of current
treatments, but also activate certain receptors which may
ment may prove to be an effective treatment. The vaccine is decrease the negative side effects of current treatments and
designed to induce antibodies that bind specifically to cocaine increase the positive effect on cognition.
in the blood and prevent it from reaching the brain. The
physiological response to cocaine is thus altered, reducing
the reinforcing properties of cocaine.

Depression MENTAL HEALTH


One medicine in development targets pathways involving
glutamate, a common neurotransmitter found in the brain and
involved in memory, learning and cognition. Dysfunction of the
glutamate system can lead to seizures and cell death and may
contribute to some mental disorders. The medicine targets a
specific type of glutamate receptor in the brain—the NMDA DEPRESSION
receptor—resulting in rapid-onset of therapeutic effects—from
weeks to hours. An intranasal formulation of the medicine is
being developed for treatment-resistant depression.
AFFECTS

21
A medicine in development for major depressive disorder in
patients who have not responded to current treatments com-
bines an opioid modulator with an opioid stimulator. Opioid MILLION
stimulators have been shown to help in the treatment of AMERICAN ADULTS
depression, but they can also be highly addictive. By coupling
the stimulant with an opioid receptor blocker, the addictive Source: NIMH.

qualities are “decoupled” from the antidepressant properties.

4 Medicines in Development for Mental Health 2014


Key Issues

MENTAL HEALTH “We are still at the beginning of what


could be an era of brain exploration,
with great promise for understanding
stress disorder
post-traumatic

social phobia more about how each of us thinks and


obsessive-compulsive
dreams and loves, but perhaps even
greater promise for helping people with
anxiety panic disorder mental disorders.”
disorder

—Tom Insel, M.D.

ANXIETY
Director, National Institute of Mental Health

DISORDERS
AFFECT
academic-industry research collaboration dedicated to
finding new methods for developing drugs for schizophre-

40 MILLION
AMERICAN ADULTS
nia and depression. NEWMEDS is based in Europe but
involves many U.S. industry partners. Ultimately, the goal
of NEWMEDS is to develop new approaches for shorter
Source: NIMH.
and more efficient trials of new medications, with clinical
trials that may require fewer patients and give faster results.

Collaborative Research Partnerships


Are Critical to Advancing Science BRAINSPAN ATLAS OF THE
Collaboration among partners in the entire biomedical
DEVELOPING HUMAN BRAIN
ecosystem is critical to helping advance scientific understand- The “BrainSpan Atlas” is a comprehensive three-
ing of brain disorders, one of the most complex areas for dimensional atlas of the developing human brain
researchers. Federal research institutions, academia, bio-
that incorporates gene activity along with anatomical
reference atlases and neuroimaging data. The Atlas
pharmaceutical research companies and patient communities
highlights the transcriptome—a map showing when
all play an important role in furthering research into those and where genes are turned on in the brain—and
disorders. Some examples of key partnerships include: anatomy of the human brain during mid-term
pregnancy. Some researchers have already had success
• One Mind, a non-profit organization that brings together using the BrainSpan map to associate genes in the
a broad international coalition of scientists, advocates, developing brain with the adult brain, whereas before
philanthropists, government, and the pharmaceutical and they were seemingly unrelated.
health care industries, is dedicated to aiding the accelera- The BrainSpan Atlas was developed by a consortium of
tion of development of new treatments for brain disorders public and private institutions led by the Allen Institute
and injury. The organization’s 10-year plan addresses current for Brain Science in Seattle and funded through awards
gaps in basic science, ways to expand translational efforts, from the NIMH. It is available free to the public and is
and regulatory reforms that are necessary to achieve their intended to help researchers better understand mental
mission of cures in the next decade through data sharing,
disorders that may result from changes or problems
occurring early during brain development, such as
cooperative efforts and public-private partnerships.
autism and schizophrenia. This understanding may in
• NEWMEDS (Novel Methods leading to New Medica-
turn provide new insight into therapeutic targets and
improved screening and diagnosis.
tions in Depression and Schizophrenia) is an international,

Medicines in Development for Mental Health 2014 5


Key Issues

Early Scientific Discoveries


MENTAL HEALTH
Early-stage research findings are critical for understanding
GENETIC ILLNESS

YMPTOMS
disease pathology and developing new, effective treatments.
DISORGANIZED PSYCHOSIS
O
Many of the challenges in mental health research reflect the
THOUGHT PROCESS HALLUCINATIONS reality that we are still learning how the human brain works.
DIAGNOSISCOGNITIVE PSYCHOLOGICAL
TREATMENTGEN
SCHIZOPHRENIA
BRAIN CHEMISTRY DELUSIONS
Also, research efforts are complicated by the fact that many
disorders fall under the broad umbrella of mental health,
ENETIC

ranging from anxiety to depression to developmental disor-


TREATMENT DISORDER
DISORDE
DIAGNOSIS

ders to substance use disorders. Early scientific discoveries


EMOTIONA
DI

can provide biopharmaceutical companies with potential new


PSYCHOSIS treatment pathways for research or for refinement of existing
AFFECTS
known pathways. Some recent discoveries include:

2.4 MILLION • The human genome is under examination by research-


AMERICAN ADULTS based institutions around the globe looking for genetic
associations in schizophrenia and other mental disorders.
Source: NIMH.
Scientists have identified gene variants and mutations
in people with schizophrenia and compared them to
healthy people, identifying the location and patterns of
• Fast-Fails Trials (FAST) is an NIMH program in collabo- the mutations. Scientists are optimistic that those dis-
ration with select academic research teams working to coveries will reveal clues about the underlying biology of
accelerate the pace of psychiatric drug discovery through schizophrenia.
rapid testing of new or repurposed compounds for their
potential as psychiatric medications.

• The Army Study to Assess Risk and Resilience in Ser- MENTAL HEALTH
vicemembers (Army STARRS) is an unparalleled research
study on suicide prevention—a critical area of research
for the Army, other military personnel and the general
population. The 5-year study, one of the largest and most
complex studies ever administered by NIMH, is being
conducted in collaboration with select academic research
teams.

• The White House Brain Initiative (Brain Research


through Advancing Innovative Neurotechnologies) is a SUBSTANCE USE/
public-private partnership for brain research focused on ADDICTIVE DISORDERS
$600
increasing our understanding of the human brain by ac- COST THE
U.S. MILLION
celerating the development and application of innovative
MORE THAN YEARLY
technologies. Through those technologies, researchers will
be able to produce a new dynamic picture of the brain
that, for the first time, will show how individual cells and Source: National Institute on Drug Abuse.

complex neural circuits interact in both time and space.

6 Medicines in Development for Mental Health 2014


Key Issues

• New data from a team of researchers from Emory


University, the University of Miami, and Scripps Re- ADHERENCE TO TREATMENT
search Institute have identified a potential new treat- CAN IMPROVE HEALTH
ment for post-traumatic stress disorder (PTSD). In mice,
OUTCOMES AND COSTS
the compound reduced PTSD-like symptoms after the
animals were exposed to stress. Researchers believe the Adherence to medication dosing and scheduling
compound affects the fear learning process. Such findings is important to treat mental health conditions
effectively and help control costs by limiting relapses,
could potentially lead to a treatment that could prevent
hospitalizations and limiting indirect costs like lost
PTSD after an individual is exposed to a psychologically
productivity. Data highlighted by the American
traumatic event. Pharmacists Association estimated that nonadherence
rates are between 30 percent and 65 percent in
• New research from Oregon Health & Science University’s
individuals diagnosed with a severe mental illness.
Vollum Institute is giving scientists a “never-before-seen” Many barriers to adherence have been identified,
view of how nerve cells communicate with each other including patient and family attitudes, treatment-
and possibly a better understanding of how antidepres- related issues (side effects), health system factors,
sants work in the human brain. Using special methods, cultural influences, and the perceived stigma
scientists focused on the structure of the dopamine associated with mental disorders.
transporter, which helps regulate dopamine levels in the
brain—abnormal levels of dopamine are present in many
disorders, including depression. The more detailed view
and understanding of the dopamine transporter could
help biopharmaceutical researchers develop more effective
antidepressants.

Medicines in Development By Disease and Phase


Some medicines are listed in more than one category.

All Medicines 119

Anxiety Disorders 15
Attention-Deficit
Hyperactivity/Disorder 15
Autism Spectrum
Disorders 6

Bipolar Disorders 5
Application
Depression 29 Submitted
Phase III
Eating Disorders 2 Phase II

Schizophrenia 36 Phase I

Substance Use 20
Disorders
Tic Disorders 3

Other Disorders 2

Medicines in Development for Mental Health 2014 7


Facts

Selected Facts about Mental Health in the United States


Overview1 social and personal impairment as well as other psychiat-
ric conditions.2
• An estimated 61.5 million Americans—about one in four
adults—suffer from a diagnosable mental disorder in a • It is estimated that depression occurs in 50 percent of pa-
given year. About 13.6 million Americans, or 1 in 17, suf- tients diagnosed with schizophrenia, and about 47 percent
fer from a serious mental illness. have a lifetime diagnosis of comorbid substance abuse.3

• About 20 percent of young Americans ages 13 to 18


Anxiety Disorders1
and 13 percent of those ages 8 to 15 experience severe
mental disorders in a given year. • Anxiety disorders, which include panic disorder, obses-
sive-compulsive disorder, PTSD, generalized anxiety
• Mental disorders are the leading cause of disability in disorder, phobias and social anxiety disorder, affect
the United States. Many people suffer from more than some 40 million adults ages 18 and older, or about 18
one mental disorder at a given time. Nearly half (45 percent of people in that age group in a given year.
percent) of those with any mental disorder meet criteria
for two or more disorders. • Generalized anxiety disorder affects about 6.8 million
American adults, including twice as many women as men.
• In 2011, suicide was the tenth leading cause of death in
the United States, accounting for 38,285 deaths. Risk • Obsessive-compulsive disorder affects about 2.2 million
factors for suicide include depression and other mental American adults, striking men and women in roughly
disorders or a substance use disorder (often in combi- equal numbers.
nation with other mental disorders).
• Panic disorder affects about 6 million American adults
• Serious mental illnesses cost the United States more and is twice as common in women as men.
than $317 billion annually in lost wages, health care ex-
• PTSD affects about 7.7 million American adults, but it
penditures, and disability benefits. Lost earnings alone
can occur at any age, including childhood. Women are
account for $193 billion per year.
more likely to develop PTSD than men, and there is
some evidence that susceptibility to the disorder may
Co-occurrence/Comorbidity in Mental Health
run in families.
• Treatment challenges are exacerbated by co-occurrence
or comorbidity of mental disorders. One study found • Social phobia affects about 15 million American adults.
that nearly half of individuals seeking treatment for sub- Women and men are equally likely to develop the disorder.
stance use disorder meet diagnostic criteria for PTSD,
and individuals with co-occurring PTSD and substance Attention-Deficit/Hyperactivity Disorder (ADHD)
use disorder tended to have poorer treatment outcomes • ADHD is the most common mental disorder in children
compared to those without the comorbidity.2 and adolescents.1 It affects as many as one in every 20
children, and boys are three to four times more likely
• About one-third of people diagnosed with major depres-
than girls to experience the disorder.4 About 4 percent
sive disorder also have substance use disorder, and the
of adults ages 18 to 44 are affected by ADHD.1
comorbidity results in a higher risk of suicide and greater

8 Medicines in Development for Mental Health 2014


Facts

• Although most children with ADHD have normal or • Major depressive disorder is the leading cause of dis-
above-normal intelligence, 40 percent to 60 percent ability among Americans ages 15-44. It affects nearly
have serious learning difficulties.4 15 million U.S. adults.

• Children and adolescents with ADHD are more likely Eating Disorders1
than children without the disorder to suffer from other
• In their lifetime, an estimated 0.6 percent of the U.S. adult
mental disorders.4
population will suffer from anorexia, 1.0 percent from
Autism Spectrum Disorders5 bulimia, and 2.8 percent from a binge-eating disorder.

• In 2010, about 1 in 68 8-year-olds were identified with • Women are much more likely than men to develop an
autism spectrum disorder (ASD).* The 2010 estimate is eating disorder. They are three times as likely to experi-
roughly 30 percent higher than the estimate for 2008 ence anorexia (0.9 percent of women vs. 0.3 percent of
(1 in 88), 60 percent higher than the estimate for 2006 men) and bulimia (1.5 percent of women vs. 0.5 percent
(1 in 110), and 120 percent higher than the estimates of men) during their lives. They are also 75 percent more
for 2002 and 2000 (1 in 150). (The exact cause of the likely to have a binge-eating disorder (3.5 percent of
increase is unknown, but researchers believe some of it women vs. 2.0 percent of men).
may be due to the way children are identified, diagnosed,
and served in their local communities.) Schizophrenia
• Approximately 2.4 million American adults age 18 and
• Boys were almost five times more likely to be identified
older have schizophrenia in a given year. It affects men
with ASD than girls in 2010. About 1 in 42 boys and 1 in
and women with equal frequency. Schizophrenia often
189 girls were identified with ASD.
first appears in men in their late teens or early twenties.
Depression1 In contrast, women are generally affected in their twen-
ties or early thirties.1
• Mood disorders, which include major depressive dis-
order, dysthymic disorder, and bipolar disorder, affect • The appearance of schizophrenic symptoms before age
nearly 21 million adults, or about 9.5 percent of the U.S. 12 is rare—less than one-sixtieth as common as the
population age 18 and older in a given year. adult-onset type. Neurodevelopmental damage seems to
be greater in childhood schizophrenia than in the adult-
• Bipolar disorder affects approximately 5.7 million Ameri-
onset type.5
can adults, or about 2.6 percent of the U.S. population
age 18 and older in a given year. The median age of Substance Use/Addictive Disorders
onset for bipolar disorder is 25 years.
• An estimated 17 million Americans have an alcohol use
• Depression can strike anyone regardless of age, ethnic disorder—a medical term that includes both alcoholism
background, socioeconomic status, or gender; however, and harmful drinking that does not reach the level of
studies have found that depression is about twice as dependence.6
common in women as in men. In any given one year
• Each year in the United States, nearly 80,000 people die
period, depressive illnesses affect more than 12 million
from alcohol-related causes, making it the third leading
women and more than 6 million men.
preventable cause of death in our country.6

* Estimates are based on information collected from the health and special education records of 8-year-old children living in areas of 11 different states. They
do not represent the entire population of children in the United States.

Medicines in Development for Mental Health 2014 9


Facts

• Illicit drug use in America has been increasing. In 2012, Sources:


an estimated 23.9 million Americans ages 12 or older—
1. National Institute of Mental Health, www.nimh.nih.gov
or 9.2 percent of the population—had used an illicit drug
or abused a psychotherapeutic medication (such as a 2. National Center for Biotechnology Information,
pain reliever, stimulant, or tranquilizer) in the past month. www.ncbi.nlm.nih.gov
That was up from 8.3 percent in 2002.7 3. Schizophrenia Bulletin,
www.schizophreniabulletin.oxfordjournals.org
• In 2008 there were 1.9 million cocaine users. Adults
ages 18 to 25 have a higher rate of current cocaine use 4. Mental Health America, www.mentalhealthamerica.net
than any other age group. Overall, men report higher 5. U.S. Centers for Disease Control and Prevention,
rates of cocaine use than women.8 www.cdc.gov

• Estimates of the total overall costs of substance abuse 6. National Institute on Alcohol Abuse and Alcoholism,
in the United States, including productivity and health- www.niaaa.nih.gov
and crime-related costs, exceed $600 billion annually. 7. National Institute on Drug Abuse, www.drugabuse.gov
That includes approximately $193 billion for illicit drugs, 8. Substance Abuse and Mental Health Services Adminis-
$193 billion for tobacco, and $235 billion for alcohol.7 tration, www.samhsa.gov

Tourette’s Syndrome9 9. National Alliance on Mental Illness, www.nami.org

• Approximately 1 in 200 children have Tourette’s syn-


drome.

10 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Anxiety Disorders
Product Name Sponsor Indication Development Phase*

aloradine Pherin Pharmaceuticals social anxiety disorder Phase II completed


(sensory receptor cell modulator) Los Altos, CA (social phobia) www.pherin.com

alprazolam patch Nuvo Research panic disorder Phase I


Mississauga, Canada www.nuvoresearch.com

AVN-101 AllaChem anxiety Phase II


(5-HT6 receptor antagonist) Hallandale Beach, FL www.allachem.com
Avineuro www.avineuro.com
San Diego, CA

AVP-923 Avanir aggitation in Alzheimer’s disease Phase II


(dextromethorphan/quinidine Aliso Viejo, CA www.avanir.com
fixed-dose combination)

bitopertin Roche obsessive-compulsive disorder Phase II


(GlyT1 inhibitor) Nutley, NJ (see also schizophrenia) www.roche.com

brexpiprazole Lundbeck agitation associated with Phase III


(dopamine partial agonist) Deerfield, IL Alzheimer’s disease www.lundbeck.com
Otsuka Pharmaceutical (see also ADHD, depression, www.otsuka.com
Rockville, MD schizophrenia)
----------------------------------------- -----------------------------------------
post-traumatic stress disorder Phase III
(PTSD) www.lundbeck.com
www.otsuka.com

Brintellix® Lundbeck generalized anxiety disorder Phase III


vortioxetine Deerfield, IL (see also depression) www.lundbeck.com
Takeda Pharmaceuticals www.takeda.com
Deerfield, IL ----------------------------------------- -----------------------------------------
anxiety disorders Phase II
(children and adolescents) www.lundbeck.com
www.takeda.com

ELND005 Transition Therapeutics agitation and aggression associated Phase II


Toronto, Canada with Alzheimer’s disease www.transitiontherapeutics.com
(Fast Track)

ganaxolone Marinus Pharmaceuticals PTSD Phase II


New Haven, CT www.marinuspharma.com

guanfacine extended release Shire generalized anxiety disorder Phase II completed


(SPD503) Wayne, PA separation anxiety disorder, www.shire.com
social phobia

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

Medicines in Development for Mental Health 2014 11


Medicines in Development for Mental Health

Anxiety Disorders
Product Name Sponsor Indication Development Phase

IW-2143 Bionomics anxiety Phase I


Thebarton, Australia www.bionomics.com.au
Ironwood Pharmaceuticals www.ironwoodpharma.com
Cambridge, MA

JNJ-42165279 Janssen Research & Development anxiety disorders Phase I


Raritan, NJ www.janssenrnd.com

nepicastat Biotie Therapies PTSD Phase II


(SYN117) Turku, Finland (see also substance use) www.biotie.com
U.S. Department of Defense
Washington, DC

SRX246 Azevan Pharmaceuticals stress-related affective disorders Phase I


(vasopressin 1a receptor Bethlehem, PA www.azevan.com
antagonist)

Viibryd® Forest Laboratories generalized anxiety disorder Phase III


vilazodone New York, NY (see also depression) www.frx.com

Attention-Deficit/Hyperactivity Disorder
Product Name Sponsor Indication Development Phase

ADHD therapeutic Neos Therapeutics attention-deficit/hyperactivity in clinical trials


Grand Prairie, TX disorder (ADHD) www.neostx.com

AR08 Arbor Pharmaceuticals ADHD Phase II


(adrenergic receptor agonist) Atlanta, GA www.arborpharma.com

ATS Noven Pharmaceuticals ADHD Phase II


(dexamfetamine transdermal) Miami, FL www.noven.com

brexpiprazole Lundbeck ADHD (adults) Phase II


(dopamine partial agonist) Deerfield, IL (see also anxiety, depression, www.lundbeck.com
Otsuka Pharmaceutical schizophrenia) www.otsuka.com
Rockville, MD

EB-1020 Euthymics Biosciences ADHD (adults) Phase II


(triple reuptake inhibitor) Cambridge, MA www.euthymics.com

edivoxetine Eli Lilly ADHD Phase II/III


Indianapolis, IN www.lilly.com

12 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Attention-Deficit/Hyperactivity Disorder
Product Name Sponsor Indication Development Phase

eltoprazine Amarantus Bioscience ADHD (adults) Phase II


San Francisco, CA www.amarantus.com

HLD200 Highland Therapeutics ADHD (pediatric) Phase III


(methylphenidate modified Toronto, Canada www.highlandtherapeutics.com
release) Ironshore Pharmaceuticals
and Development
Toronto, Canada

metadoxine extended release Alcobra ADHD (adults) Phase II/III


Tel-Aviv, Israel www.alcobra-pharma.com

NT0102 Neos Therapeutics ADHD (pediatric) Phase III


Grand Prairie, TX www.neostx.com

NT0202 Neos Therapeutics ADHD application submitted


(amphetamine polistirex Grand Prairie, TX www.neostx.com
disintegrating tablet,
extended release)

ORADUR®-ADHD DURECT ADHD Phase I


methylphenidate sustained release Cupertino, CA www.durect.com

SEP-225289 Sunovion ADHD Phase II


(triple reuptake inhibitor) Marlborough, MA www.sunovion.com

SPN-810 Supernus Pharmaceuticals impulsive aggression in ADHD Phase II completed


(molindone) Rockville, MD www.supernus.com

SPN-812 Supernus Pharmaceuticals ADHD (adults) Phase II completed


(adrenergic uptake inhibitor) Rockville, MD www.supernus.com

Autism Spectrum Disorders


Autism spectrum disorders, although most commonly referred to as developmental disorders, are included here because
individuals with autism can have mental health-related symptoms.

Product Name Sponsor Indication Development Phase

AT001 Autism Therapeutics autism Phase III


(fluoxetine rapid dissolve) New York, NY (repetitive behaviors) www.autismtherapeutics.com
ORPHAN DRUG (Fast Track)

CM-AT Curemark autism application submitted


Rye, NY (Fast Track) www.curemark.com

Medicines in Development for Mental Health 2014 13


Medicines in Development for Mental Health

Autism Spectrum Disorders


Product Name Sponsor Indication Development Phase

CNDO-201 Coronado Biosciences autism Phase II


(Trichuris suis ova) Burlington, MA www.coronadobiosciences.com

memantine Forest Laboratories pervasive developmental disorder Phase II completed


New York, NY not otherwise specified, Asperger’s www.frx.com
syndrome, autism
(pediatric)

RG7314 Roche autism Phase II


(vasopressin-1 receptor Nutley, NJ www.roche.com
antagonist)

syntocinon nasal spray Retrophin autism Phase II


New York, NY (see also schizophrenia) www.retrophin.com

Bipolar Disorders
Product Name Sponsor Indication Development Phase

Abilify® Maintena® Otsuka Pharmaceutical bipolar disorder Phase III


aripiprazole for extended release Rockville, MD www.otsuka.com
injectable suspension
(depot injection)

cariprazine Forest Laboratories manic or mixed episodes associated application submitted


New York, NY with bipolar I disorder www.frx.com
(see also depression, schizophrenia)

Latuda® Sunovion bipolar maintenance Phase III


lurasidone Marlborough, MA (see also depression) www.sunovion.com

Rozerem® Takeda Pharmaceutical bipolar 1 disorder Phase III


ramelteon Deerfield, IL www.takeda.com
(sublingual formulation)

Saphris® Forest Laboratories bipolar disorder Phase III


asenapine New York, NY (children and adolescents) www.frx.com
Merck www.merck.com
Whitehouse Station, NJ

14 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Depression
Product Name Sponsor Indication Development Phase

ademetionine MSI Methylation Sciences major depressive disorder Phase II


(MSI-195) Burnaby, Canada www.methylationsciences.com

ALKS 5461 Alkermes major depressive disorder Phase III


(buprenorphine/samidorphan) Waltham, MA (Fast Track) www.alkermes.com

amitifadine Euthymics Bioscience major depressive disorder Phase II/III


(triple reuptake inhibitor) Cambridge, MA www.euthymics.com

armodafinil Teva Pharmaceutical major depressive disorder associated Phase III completed
North Wales, PA with bipolar 1 disorder www.tevapharm.com
(see also eating disorders)

AVP-786 Avanir Pharmaceuticals treatment-resistant depression Phase I completed


(deuterium modified Aliso Viejo, CA www.avanir.com
dextromethorphan and ultra-low Concert Pharmaceuticals www.concertpharma.com
dose quinidine) Lexington, MA

AZD6423 AstraZeneca suicidal ideation Phase I


(NMDA modulator) Wilmington, DE www.astrazeneca.com

Botox® Allergan major depressive disorder Phase II


onabotulinumtoxinA Irvine, CA www.allergan.com

brexpiprazole Lundbeck major depressive disorder Phase III


(dopamine partial agonist) Deerfield, IL (adjunctive treatment) www.lundbeck.com
Otsuka Pharmaceutical (see also ADHD, anxiety, www.otsuka.com
Rockville, MD schizophrenia)

Brintellix® Lundbeck depressive disorders Phase II


vortioxetine Deerfield, IL (children and adolescents) www.lundbeck.com
Takeda Pharmaceutical (see also anxiety) www.takeda.com
Deerfield, IL

cariprazine Forest Laboratories bipolar depression, major depressive Phase II


New York, NY disorder (adjunctive treatment) www.frx.com
(see also bipolar, schizophrenia)

CERC-301 Cerecor major depressive disorder Phase II


(NR2B antagonist) Baltimore, MD (Fast Track) www.cerecor.com
----------------------------------------- -----------------------------------------
active suicidal ideation Phase II
www.cerecor.com

DSP-1053 Sunovion major depressive disorder Phase I


(serotonin uptake inhibitor) Marlborough, MA www.sunovion.com

Medicines in Development for Mental Health 2014 15


Medicines in Development for Mental Health

Depression
Product Name Sponsor Indication Development Phase

esketamine Janssen Research & Development treatment-resistant major depressive Phase II


(intranasal) Raritan, NJ disorder www.janssenrnd.com
(Fast Track)

GLYX-13 Naurex major depressive disorder Phase II


Evanston, IL (Fast Track) www.naurex.com

HT-2157 Dart NeuroScience major depressive disorder Phase II


(GALR3 antagonist) San Diego, CA www.dartneuroscience.com

JNJ-42847922 Janssen Research & Development major depressive disorder Phase I


Raritan, NJ www.janssenrnd.com

Latuda® Sunovion major depressive disorder with mixed Phase III


lurasidone Marlborough, MA features www.sunovion.com
(see also bipolar)

LY03005 Luye America Pharmaceuticals major depressive disorder Phase I


Princeton, NJ www.luye.cn

LY2940094 Eli Lilly major depressive disorder Phase II


(NOC-1 antagonist) Indianapolis, IN (see also substance use) www.lilly.com

mifepristone Corcept Therapeutics major depression disorder with Phase III


Menlo Park, CA psychotic features www.corcept.com

MIN-117 Minerva Neurosciences major depressive disorder Phase II


(5-HT1A/5-HTT receptor Cambridge, MA www.minervaneurosciences.com
antagonist)

NRX-1074 Naurex major depressive disorder Phase I


(NMDA receptor agonist) Evanston, IL www.naurex.com

NSI-189 Neuralstem major depressive disorder Phase I


(stimulating neurogenesis) Germantown, MD www.neuralstem.com

Pristiq® Pfizer major depressive disorder Phase III


desvenlafaxine New York, NY (children and adolescents) www.pfizer.com

RG1578 Roche major depressive disorder Phase II


(mGluR2) Nutley, NJ www.roche.com

RG7090 Roche treatment-resistant depression Phase II


(mGluR5 antagonist) Nutley, NJ www.roche.com

16 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Depression
Product Name Sponsor Indication Development Phase

RO4995819 Roche major depressive disorder Phase II


Nutley, NJ www.roche.com

tedatioxetine Lundbeck major depressive disorder Phase II


Deerfield, IL www.lundbeck.com
Takeda Pharmaceutical www.takeda.com
Deerfield, IL

Viibryd® Forest Laboratories major depressive disorder Phase III


vilazodone New York, NY (adolescents) www.frx.com
(see also anxiety)

Eating Disorders
Product Name Sponsor Indication Development Phase

armodafinil Teva Pharmaceutical binge-eating disorder Phase III


North Wales, PA (see also depression) www.tevapharm.com
Lindner Center of HOPE
Cincinnati, OH

LDX Shire binge-eating disorder (adults) Phase III


(lisdexamfetamine) Wayne, PA www.shire.com

Schizophrenia
Product Name Sponsor Indication Development Phase

ABT-126 AbbVie cognition impairment associated with Phase II


(alpha7 NNR antagonist) North Chicago, IL schizophrenia (CIAS) www.abbvie.com

ADX71149/JNJ-40411813 Addex Therapeutics schizophrenia Phase II


(mGlu2 PAM modulator) Geneva, Switzerland www.addextherapeutics.com
Janssen Research & Development www.janssenrnd.com
Raritan, NJ

ALKS 3831 Alkermes schizophrenia Phase II


(olanzapine/samidorphan Waltham, MA www.alkermes.com
fixed-dose combination)

AMG 581 Amgen schizophrenia Phase I


Thousand Oaks, CA www.amgen.com

Medicines in Development for Mental Health 2014 17


Medicines in Development for Mental Health

Schizophrenia
Product Name Sponsor Indication Development Phase

AQW051 Novartis Pharmaceuticals CIAS Phase II completed


(alpha7 nicotinic acetylcholine East Hanover, NJ www.novartis.com
receptor agonist)

aripiprazole lauroxil Alkermes schizophrenia Phase III


(ALKS 9072) Waltham, MA www.alkermes.com

AVL-3288 Anvyl Pharmaceuticals CIAS Phase I


(alpha7 nicotinic acetylcholine Irvine, CA www.anvylllc.com
receptor modulator)

AVN-211 AllaChem schizophrenia Phase II


(5-HT6 receptor antagonist) Hallandale Beach, FL www.allachem.com
Avineuro Pharmaceuticals www.avineuro.com
San Diego, CA

BI-409306 Boehringer Ingelheim Pharmaceuticals schizophrenia Phase I completed


Ridgefield, CT www.boehringer-ingelheim.com

bitopertin Roche schizophrenia-suboptimally Phase III


(GlyT1 inhibitor) Nutley, NJ controlled symptoms www.roche.com
(see also anxiety)

brexpiprazole Lundbeck schizophrenia Phase III


(dopamine partial agonist) Deerfield, IL (see also ADHD, anxiety, depression) www.lundbeck.com
Otsuka Pharmaceutical www.otsuka.com
Rockville, MD

cariprazine Forest Laboratories schizophrenia application submitted


New York, NY (see also bipolar, depression) www.frx.com

CEP-26401 Teva Pharmaceutical CIAS Phase I completed


(irdabisant) North Wales, PA www.tevapharm.com

encenicline Forum Pharmaceuticals CIAS Phase III


(alpha-7 agonist) Watertown, MA www.forumpharma.com

FRM-6308 Forum Pharmaceuticals schizophrenia Phase I


(PDE10 inhibitor) Watertown, MA www.forumpharma.vom

Invega® Sustenna® Alkermes schizoaffective disorder Phase III


paliperidone palmitate Waltham, MA www.alkermes.com
Janssen Research & Development www.janssenrnd.com
Raritan, NJ ----------------------------------------- -----------------------------------------
schizophrenia (3 month injectable) Phase III
www.alkermes.com
www.janssenrnd.com

18 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Schizophrenia
Product Name Sponsor Indication Development Phase

ITI-007 Intra-Cellular Therapies schizophrenia Phase II


(5-HT2A serotonin receptor New York, NY www.intracellulartherapies.com
antagonist)

ITI-214 Intra-Cellular Therapies CIAS Phase I


(PDE1 inhibitor) New York, NY www.intracellulartherapies.com
Takeda Pharmaceuticals www.takeda.com
Deerfield, IL

LY03004 Luye America Pharmaceuticals schizophrenia, schizoaffective disorder Phase I


(risperidone controlled release) Princeton, NJ www.luye.cn

MIN-101 Minerva Neurosciences schizophrenia Phase II


(5-HT2A/sigma-2 receptor Cambridge, MA www.minervaneurosciences.com
antagonist)

NW-3509 Newron Pharmaceuticals schizophrenia Phase I


(potent sodium channel blocker) Bresso, Italy www.newron.com

OMS824 Omeros schizophrenia Phase II


(PDE10 inhibitor) Seattle, WA www.omeros.com

PF-02545920 Pfizer schizophrenia Phase II


(PDE10 inhibitor) New York, NY (adjunctive treatment) www.pfizer.com

PF-04958242 Pfizer schizophrenia Phase I


(AMPA receptor modulator) New York, NY www.pfizer.com

PF-06412562 Pfizer CAIS Phase I


New York, NY www.pfizer.com

pimavanserin ACADIA Pharmaceuticals Parkinson’s disease psychosis Phase III


San Diego, CA www.acadia-pharm.com
----------------------------------------- -----------------------------------------
Alzheimer’s disease psychosis, Phase II
schizophrenia www.acadia-pharm.com

RBP-7000 Reckitt Benckiser Pharmaceutical schizophrenia Phase III


(dopamine-D2/serotonin-2 Richmond, VA www.rb.com
antagonist)

Relday™ DURECT schizophrenia Phase I


risperidone controlled release Cupertino, CA www.durect.com
Zogenix www.zogenix.com
San Diego, CA

Medicines in Development for Mental Health 2014 19


Medicines in Development for Mental Health

Schizophrenia
Product Name Sponsor Indication Development Phase

RG7203 Roche schizophrenia Phase I


(PDE10A inhibitor) Nutley, NJ www.roche.com

RO5545965 Roche schizophrenia Phase I


Nutley, NJ www.roche.com

RP5063 Reviva Pharmaceuticals schizophrenia, schizoaffective disorder Phase II


(partial agonist of dopamine and San Jose, CA www.revivapharma.com
serotonin)

Saphris® Forest Laboratories schizophrenia (adolescents) Phase III completed


asenapine New York, NY (see also bipolar) www.frx.com
Merck www.merck.com
Whitehouse Station, NJ

SEP-363856 Sunovion schizophrenia Phase I


Marlborough, MA www.sunovion.com

syntocinon nasal spray Retrophin schizophrenia Phase II


New York, NY (see also autism) www.retrophin.com

TAK-063 Takeda Pharmaceuticals schizophrenia Phase I


(PDE10A inhibitor) Deerfield, IL www.takeda.com

zicronapine Lundbeck schizophrenia Phase III


Deerfield, IL www.lundbeck.com

Substance Use/Addictive Disorders


Product Name Sponsor Indication Development Phase

ABT-436 AbbVie alcohol use disorder Phase II


(selective vasopressin receptor North Chicago, IL www.abbvie.com
antagonist) National Institute on Alcohol www.niaaa.nih.gov
Abuse and Alcoholism
Bethesda, MD

AD01 ADial Pharmaceuticals alcohol use disorder Phase II


(ondansetron/topiramate) Charlottesville, VA www.adialpharma.com

AD04 ADial Pharmaceuticals alcohol use disorder Phase II


(low-dose ondansetron) Charlottesville, VA www.adialpharma.com

Bunavail™ BioDelivery Sciences International opioid use disorder, opioid abuse application submitted
buprenorphine/naloxone Raleigh, NC www.bdsi.com
transmucosal

20 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Substance Use/Addictive Disorders


Product Name Sponsor Indication Development Phase

bupropion/mecamylamine Cary Pharmaceuticals smoking withdrawal Phase I completed


once-daily tablet Great Falls, VA www.carypharma.com
(QuitPak®)

Ch-mAb7F9 InterveXion Therapeutics methamphetamine use disorder Phase I completed


(METH-mAb) Little Rock, AR www.intervexion.com

EMB-001 Embera NeuroTherapeutics cocaine use disorder Phase I completed


(metyrapone/oxazepam) Sudbury, MA www.emberaneuro.com

lofexidine US WorldMeds opioid use disorder Phase III


Louisville, KY www.usworldmeds.com
National Institute on Drug Abuse www.drugabuse.gov
Bethesda, MD

LY2940094 Eli Lilly alcohol use disorder Phase II


(NOC-1 antagonist) Indianapolis, IN (see also depression) www.lilly.com

MN-166 MediciNova methamphetamine use disorder Phase II


(ibudilast) La Jolla, CA (Fast Track) www.medicinova.com
National Institute on Drug Abuse www.drugabuse.gov
Bethesda, MD

naloxone nasal spray Lightlake Therapeutics opioid use disorder Phase II


London, United Kingdom www.lightlaketherapeutics.com
National Institute on Drug Abuse www.drugabuse.gov
Bethesda, MD

nepicastat Biotie Therapies cocaine use disorder Phase II


(SYN117) Turku, Finland (see also anxiety) www.biotie.com
National Institute on Drug Abuse www.drugabuse.gov
Bethesda, MD

OMS405 Omeros opioid use disorder, smoking Phase II


(PPAR-gamma agonist) Seattle, WA withdrawal www.omeros.com

PF-05402536 Pfizer smoking withdrawal Phase I


(smoking cessation vaccine) New York, NY www.pfizer.com

Probuphine® Braeburn Pharmaceuticals opioid use disorder application submitted


buprenorphine implant Princeton, NJ www.braeburnpharmaceuticals.com
Titan Pharmaceuticals www.titanpharm.com
South San Francisco, CA

RBP-6000 Reckitt Benckiser Pharmaceutical opioid use disorder Phase II


(buprenorphine depot) Richmond, VA www.rb.com

Medicines in Development for Mental Health 2014 21


Medicines in Development for Mental Health

Substance Use/Addictive Disorders


Product Name Sponsor Indication Development Phase

RBP-8000 Reckitt Benckiser Pharmaceutical cocaine use disorder Phase II


(cocaine esterase) Richmond, VA www.rb.com

SEL-068 Selecta Biosciences smoking withdrawal Phase I


(nicotine antibodies) Watertown, MA www.selectabio.com

TA-CD Baylor College of Medicine cocaine use disorder Phase II


(cocaine abuse vaccine) Houston, Texas www.drugabuse.gov
Celtic Pharma Holdings
Hamilton, Bermuda
National Institute on Drug Abuse
Bethesda, MD

TV-1380 Teva Pharmaceutical cocaine use disorders Phase II


(form of human plasma North Wales, PA www.tevapharm.com
butyrylcholinesterase)

TIC Disorders
Product Name Sponsor Indication Development Phase

Abilify® Otsuka Pharmaceutical Tourette’s syndrome Phase III


aripiprazole Rockville, MD www.otsuka.com
(once-weekly tablet)

AZD5213 AstraZeneca Tourette’s syndrome Phase II


(histamine-3 receptor Wilmington, DE www.astrazeneca.com
antagonist)

ecopipam Psyadon Pharmaceuticals Tourette’s syndrome Phase II


Germantown, MD www.psyadonrx.com

22 Medicines in Development for Mental Health 2014


Medicines in Development for Mental Health

Other Disorders
Product Name Sponsor Indication Development Phase

PH80-PMD Pherin Pharmaceuticals premenstrual dysphoric disorder, Phase II completed


Los Altos, CA premenstrual syndrome www.pherin.com

RG1662 Roche cognitive impairment associated with Phase I


(GABA-A alpha5 receptor Nutley, NJ Downs syndrome www.roche.com
modulator)

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 April 28, 2014. The medicines in this report include medi-
cines being developed by U.S.-based companies conducting trials in the United States and abroad, PhRMA-member compa-
nies conducting trials in the United States and abroad, and foreign companies conducting clinical trials in the United States.
The information in this report may not be comprehensive. For more specific information about a particular product, contact
the individual company directly or go to www.clinicaltrials.gov. The entire series of Medicines in Development is available
on PhRMA’s website.
A publication of PhRMA’s Communications & Public Affairs Department (202) 835-3460
www.phrma.org | www.innovation.org | www.pparx.org
Provided as a public service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association.
Copyright © 2014 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper
credit is given.

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

Medicines in Development for Mental Health 2014 23


Glossary

anxiety disorders—Anxiety is a normal combination of different symptom types. high blood pressure. They also experi-
reaction to stress and can be benefi- Those with mostly inattentive symptoms ence guilt, shame, and distress about
cial in some situations, but for some are sometimes said to have attention their binge-eating, which can lead to
people anxiety may become excessive. deficit disorder (ADD). They tend to be more binge-eating.
While people suffering may realize their less disruptive and are more likely not to
bipolar disorder—Also known as manic-
anxiety is too much, they may also be diagnosed with ADHD.
depressive illness, a brain disorder that
have difficulty controlling it, and it may
autism spectrum disorder (ASD)—ASD causes unusual shifts in mood, energy,
negatively affect their day-to-day living.
is a developmental disability that can activity levels, and the ability to carry
The wide variety of anxiety disorders
cause significant social, communica- out day-to-day tasks. Symptoms of
includes generalized anxiety disorder
tion and behavioral challenges. People bipolar disorder are severe. They are dif-
(GAD), obsessive-compulsive disorder
with ASD may communicate, interact, ferent from the normal ups and downs
(OCD), panic disorder, post-traumatic
behave, and learn in ways that are that everyone goes through from time
stress disorder (PTSD), and social
different from most other people. The to time. People with bipolar disorder
phobia. Collectively, they are among the
learning, thinking, and problem-solving experience unusually intense emotional
most common mental health disorders
abilities of people with ASD can range states that occur in distinct periods
experienced by Americans.
from gifted to severely challenged. called “mood episodes.” Each mood epi-
application submitted—An application Some people with ASD need a lot of sode represents a drastic change from
for marketing has been submitted by help in their daily lives; others need less. a person’s usual mood and behavior.
the company to the U.S. Food and Drug People with ASD often have problems An overly joyful or overexcited state is
Administration (FDA). with social, emotional, and communica- called a manic episode, and an ex-
tion skills. They might repeat certain tremely sad or hopeless state is called a
attention deficit/hyperactivity disor- behaviors and might not want change depressive episode. Sometimes, a mood
der (ADHD)—ADHD is a problem of in their daily activities. Many people episode includes symptoms of both
not being able to focus, being overac- with ASD also have different ways of mania and depression, called a mixed
tive, not being able control behavior, learning, paying attention, or reacting to state. People with bipolar disorder also
or a combination of these symptoms. things. Signs of ASD begin during early may be explosive and irritable during
For those problems to be diagnosed as childhood and typically last throughout a mood episode. Extreme changes in
ADHD, they must be out of the normal a person’s life. A diagnosis of ASD now energy, activity, sleep, and behavior
range for a person’s age and develop- includes several conditions that used to go along with those changes in mood.
ment. ADHD usually begins in childhood be diagnosed separately: autistic disor- Bipolar disorder symptoms can result
but may continue into the adult years. der, pervasive developmental disorder in damaged relationships, poor job or
It is the most commonly diagnosed not otherwise specified, and Asperger’s school performance, and even suicide.
behavioral disorder in children. ADHD syndrome. Those conditions are now all But bipolar disorder can be treated, and
is diagnosed much more often in boys called autism spectrum disorder. people with the illness can lead full and
than in girls. A combination of genes productive lives.
and environmental factors likely plays a binge-eating disorder—With binge-eat-
role in the development of the condi- ing disorder a person loses control over depression—Everyone occasionally feels
tion. Symptoms of ADHD fall into three his or her eating. Unlike bulimia nervosa, blue or sad, but those feelings are usu-
groups: not being able to focus (inatten- periods of binge-eating are not fol- ally short-lived and pass within a couple
tiveness); being extremely active (hyper- lowed by purging, excessive exercise, or of days. Depression, however, interferes
activity); and not being able to control fasting. As a result, people with binge- with daily life and causes pain for both
behavior (impulsivity). Some people with eating disorder often are overweight or the sufferers and those who care about
ADHD have mainly inattentive symp- obese. People with binge-eating disor- them. Depression is a common but seri-
toms. Some have mainly hyperactive der who are obese are at higher risk for ous illness. Major depression and persis-
and impulsive symptoms. Others have a developing cardiovascular disease and tent depressive disorder are among the

24 Medicines in Development for Mental Health 2014


Glossary

several forms of depressive disorders. where none exists or providing a therapy an overwhelming urge to repeat certain
Major depression causes severe symp- that may be potentially superior to exist- rituals or behaviors called compulsions.
toms that interfere with a person’s abil- ing therapy. Once a drug receives Fast People with OCD can’t control those
ity to work, sleep, study, eat, and enjoy Track designation, early and frequent obsessions and compulsions—the rituals
life. An episode can occur only once in communication between the FDA and a usually end up controlling them. For
a person’s lifetime, but more often, a drug company is encouraged throughout example, if people are obsessed with
person has several episodes. Persistent the entire drug development and review germs or dirt, they may develop a com-
depressive disorder causes a depressed process. The frequency of communica- pulsion to wash their hands over and
mood that lasts for at least 2 years. tion ensures that questions and issues over again. If they develop an obsession
A person diagnosed with persistent are resolved quickly, often leading to with intruders, they may lock and relock
depressive disorder may have episodes earlier drug approval and access by their doors many times before going
of major depression along with periods patients. to bed. Performing such rituals is not
of less severe symptoms, but symp- pleasurable. At best, it produces tempo-
generalized anxiety disorder (GAD)—
toms must last for 2 years. People with rary relief from the anxiety created by
While everyone worries about things
depressive illnesses do not all experi- obsessive thoughts. People with OCD
like health, money, or family problems,
ence the same symptoms. The severity, perform their rituals even though doing
people with GAD are extremely worried
frequency, and duration of symptoms so interferes with daily life, and they find
about those problems and many other
vary depending on the individual and the repetition distressing. Although most
things, even when there is little or no
his or her particular illness. A few of the adults with OCD recognize that what
reason to worry about them. They are
many signs and symptoms of depression they are doing is senseless, some adults
very anxious about just getting through
are: persistent sad, anxious, or “empty” and most children may not realize that
the day, thinking that things will always
feelings; feelings of hopelessness or pes- their behavior is out of the ordinary.
go badly. At times, worrying keeps
simism; fatigue and decreased energy;
people with GAD from doing everyday Orphan Drug—A drug to treat a dis-
difficulty concentrating, remembering
tasks. They can’t relax, startle easily, and ease that has a patient population of
details, and making decisions; overeating,
have difficulty concentrating. Often they 200,000 or less in the United States, or
or appetite loss; and thoughts of suicide,
have trouble falling asleep or staying a disease that has a patient population
or suicide attempts.
asleep. Physical symptoms that often of more than 200,000 and a develop-
Fast Track—A process designed to accompany the anxiety include fatigue, ment cost that will not be recovered
facilitate the development and expedite headaches, muscle tension, muscle from sales in the United States.
the review of drugs to treat serious aches, difficulty swallowing, trembling,
panic disorder—People with panic dis-
diseases and fill an unmet medical need. twitching, irritability, sweating, nausea,
order have sudden and repeated attacks
The status is assigned by the U.S. Food lightheadedness, having to go to the
of fear that last for several minutes.
and Drug Administration (FDA). The bathroom frequently, feeling out of
Sometimes symptoms may last longer
purpose of this process is to get impor- breath, and hot flashes.
and are called panic attacks. Panic
tant new drugs to the patient earlier.
NCE—New chemical entity. attacks are characterized by a fear of
Fast Track addresses a broad range of
disaster or of losing control even when
serious diseases. In general, determining obsessive-compulsive disorder (OCD)— there is no real danger. A person may
factors for whether a drug receives Fast People with OCD feel the need to also have a strong physical reaction dur-
Track include whether the drug will af- check things repeatedly or have certain ing a panic attack. It may feel like having
fect factors such as survival, day-to-day thoughts or perform routines and rituals a heart attack. Panic attacks can occur
functioning, or the likelihood that the over and over. The thoughts and rituals at any time, and many people with panic
disease, if left untreated, will progress associated with OCD cause distress and disorder worry about and dread the
from a less severe condition to a more get in the way of daily life. The frequent possibility of having another attack. A
serious one. Filling an unmet medical upsetting thoughts are called obsessions. person with panic disorder may become
need is defined as providing a therapy To try to control them, a person will feel discouraged and feel ashamed because

Medicines in Development for Mental Health 2014 25


Glossary

he or she cannot carry out normal rou- physical harm. The person who develops increased impulsive behaviors (e.g.,
tines like going to the grocery store or PTSD may have been the one who was sexual activities, drug and alcohol abuse,
driving. Having panic disorder can also harmed, the harm may have happened gambling, or spending large amounts
interfere with school or work. to a loved one, or the person may have of money). Many of the strategies used
witnessed a harmful event that hap- to treat both schizophrenia and affec-
Phase 0—First-in-human trials con- pened to loved ones or strangers. PTSD tive conditions can be employed for this
ducted in accordance with FDA’s 2006 was first brought to public attention in condition, including antipsychotic and
guidance on exploratory Investigational relation to war veterans, but it can result mood stabilizing medications, family
New Drug (IND) studies designed to from a variety of traumatic incidents, involvement, psychosocial strategies,
speed development of promising drugs such as a mugging, rape, being kid- self-care peer support, psychotherapy
by establishing early whether the tested napped or held captive, child abuse, and integrated care for co-occurring
compound behaves in humans as was major accidents, or natural disasters substance abuse (when appropriate).
anticipated from preclinical studies. such as floods or earthquakes.
schizophrenia—A chronic, severe, and
Phase I—Researchers test the drug in a schizoaffective disorder—A serious disabling brain disorder that has affected
small group of people, usually between mental illness that affects about one people throughout history. About 1
20 and 80 healthy adult volunteers, to in 100 people. Schizoaffective disor- percent of Americans have the illness.
evaluate its initial safety and tolerability der as a diagnostic entity has features People with the disorder may hear
profile, determine a safe dosage range, that resemble both schizophrenia and voices other people don’t hear. They
and identify potential side effects. also serious mood (affective) symp- may believe other people are reading
Phase II—The drug is given to volunteer toms. A person who has schizoaffec- their minds, controlling their thoughts,
patients, usually between 100 and 300, tive disorder will experience delusions, or plotting to harm them. That can
to determine whether the drug is effec- hallucinations, other symptoms that terrify people with the illness and make
tive, identify an optimal dose, and to are characteristic of schizophrenia, and them withdrawn or extremely agitated.
evaluate further its short-term safety. significant disturbances in their mood People with schizophrenia may not make
(e.g., affective symptoms). People who sense when they talk. They may sit for
Phase III—The drug is given to a larger, experience more than two weeks of hours without moving or talking. Some-
more diverse patient population, often psychotic symptoms in the absence times people with schizophrenia seem
involving between 1,000 and 3,000 of severe mood disturbances—and perfectly fine until they talk about what
patients (but sometimes many more then have symptoms of either depres- they are really thinking. Families and
thousands), to generate statistically sion or bipolar disorder—may have society are affected by schizophrenia,
significant evidence to confirm its safety schizoaffective disorder. Schizoaffective too. Many people with schizophrenia
and effectiveness. Phase III studies are disorder is thought to be between the have difficulty holding a job or caring
the longest studies and usually take bipolar and schizophrenia diagnoses for themselves, so they rely on others
place in multiple sites around the world. as it has features of both. Depressive for help. Cognitive symptoms are subtle
symptoms associated with schizoaffec- and may be difficult to recognize as part
post-traumatic stress disorder (PTSD)—
tive disorder can include—but are not of the disorder. Often, they are detected
When in danger, it’s natural to feel
limited to—hopelessness, helplessness, only when other tests are performed.
afraid. That fear triggers the “fight-or-
guilt, worthlessness, disrupted appetite, Cognitive symptoms include the follow-
flight” response as a healthy reaction
disturbed sleep, inability to concentrate, ing: poor “executive functioning” (the
meant to protect a person from harm.
and depressed mood (with or without ability to understand information and
But in PTSD, that reaction is changed
suicidal thoughts). Manic (bipolar) symp- use it to make decisions); trouble focus-
or damaged. People who have PTSD
toms associated with schizoaffective ing or paying attention; problems with
may feel stressed or frightened even
disorder can include increased energy, “working memory” (the ability to use in-
when they’re no longer in danger. PTSD
decreased sleep (or decreased need for formation immediately after learning it).
develops after a terrifying ordeal that
sleep), distractibility, fast speech, and Cognitive symptoms often make it hard
involved physical harm or the threat of

26 Medicines in Development for Mental Health 2014


Glossary

to lead a normal life and earn a living. substance use disorders—A term used harmful consequences. It is considered a
They can cause great emotional distress. to characterize illnesses associated with brain disease because drugs change the
Treatment helps relieve many symptoms drug use. There are two broad catego- brain—its structure and how it works.
of schizophrenia, but most people who ries: substance abuse and substance Those brain changes can be long lasting
have the disorder cope with symptoms dependence. Both are associated with and can lead to many harmful, often
throughout their lives. a maladaptive pattern of substance self-destructive, behaviors.
use that leads to clinically significant
social phobia (social anxiety disorder)— impairment. Drug abuse includes such
Tourette’s syndrome (TS)—A neurologi-
Social phobia is a strong fear of being symptoms as: failure to fulfill major
cal disorder characterized by repetitive,
judged by others and of being embar- role obligations; legal problems; use in
involuntary movements and vocaliza-
rassed. The fear can be so strong that situations that are physically hazardous;
tions called tics. The early symptoms of
it gets in the way of going to work or and continued use despite persistent
TS are typically noticed first in child-
school or doing other everyday things. social or interpersonal problems. The
hood, with the average onset between
Meeting new people or giving a public term dependence includes such symp-
the ages of 3 and 9. TS occurs in people
speech can make anyone nervous, but toms as: drug taking in larger amounts
from all ethnic groups; males are af-
people with social phobia worry about than intended; inability to cut down on
fected about three to four times more
such things for weeks before they hap- drug use; a great deal of time spent in
often than females. It is estimated that
pen. People with social phobia are afraid activities necessary to obtain the drug;
200,000 Americans have the most
of doing common things in front of and continued use despite knowledge
severe form of TS, and as many as 1
other people. For example, they might of health or social problems caused by
in 100 exhibit milder and less complex
be afraid to sign a check in front of a the drug. Dependence may or may not
symptoms such as chronic motor or
cashier at the grocery store, or they include “physical dependence,” defined
vocal tics. Although TS can be a chronic
might be afraid to eat or drink in front by withdrawal symptoms when drug use
condition with symptoms lasting a
of other people. Most people who have is abruptly ceased, and “tolerance,” the
lifetime, most people with the condition
social phobia know that they shouldn’t need for more of a drug to achieve a
experience their worst tic symptoms in
be as afraid as they are, but they can’t desired effect. The term “dependence”
their early teens, with improvement oc-
control their fear. For some people, can also refer to “addiction.” Addiction
curring in the late teens and continuing
social phobia is a problem only in certain is defined as a chronic, relapsing brain
into adulthood.
situations, while others have symptoms disease that is characterized by com-
in almost any social situation. pulsive drug seeking and use, despite

Medicines in Development for Mental Health 2014 27


The Drug Discovery, Development and Approval Process

Developing a new medicine takes an average of 10-15 years;


For every 5,000-10,000 compounds in the pipeline, only 1 is approved.

Drug Discovery and Development: A LON G , RISKY ROAD


DRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG

PHASE 4: POST-M AR K ET I N G SU RVEI L L A N C E


P R E - DI S COVERY

5,000 – 10,000 250 5


COMPOUNDS ONE FDA-
APPROVED
DRUG

PHASE PHASE PHASE


1 2 3

NDA SUBMIT T ED
IND SUBMIT T ED

NUMBER OF VOLUNTEERS

20 –80 100 – 300 1,000 – 3,000


0. 5 – 2
3 – 6 YEARS 6 – 7 Y EARS Y EARS

The Drug Development and Approval Process


The U.S. system of new drug approvals is in people. The IND shows results of previous ate statistically significant evidence to confirm
perhaps the most rigorous in the world. experiments; how, where and by whom the new its safety and effectiveness. They are the lon-
studies will be conducted; the chemical structure gest studies, and usually take place in multiple
It takes 10-15 years, on average, for an experi-
of the compound; how it is thought to work in sites around the world.
mental drug to travel from lab to U.S. patients,
the body; any toxic effects found in the animal
according to the Tufts Center for the Study of New Drug Application (NDA)/Biologic License
studies; and how the compound is manufac-
Drug Development. Only five in 5,000 com- Application (BLA). Following the completion
tured. All clinical trials must be reviewed and ap-
pounds that enter preclinical testing make it to of all three phases of clinical trials, a company
proved by the Institutional Review Board (IRB)
human testing. And only one of those five is analyzes all of the data and files an NDA or BLA
where the trials will be conducted. Progress
approved for sale. with FDA if the data successfully demonstrate
reports on clinical trials must be submitted at
both safety and effectiveness. The applications
On average, it costs a company $1.2 billion, least annually to FDA and the IRB.
contain all of the scientific information that the
including the cost of failures, to get one new
Clinical Trials, Phase I—Researchers test the company has gathered. Applications typically
medicine from the laboratory to U.S. patients,
drug in a small group of people, usually between run 100,000 pages or more.
according to a recent study by the Tufts Center
20 and 80 healthy adult volunteers, to evaluate
for the Study of Drug Development. Approval. Once FDA approves an NDA or BLA,
its initial safety and tolerability profile, deter-
the new medicine becomes available for physi-
Once a new compound has been identified in mine a safe dosage range, and identify potential
cians to prescribe. A company must continue
the laboratory, medicines are usually developed side effects.
to submit periodic reports to FDA, including
as follows:
Clinical Trials, Phase II—The drug is given any cases of adverse reactions and appropriate
Preclinical Testing. A pharmaceutical company to volunteer patients, usually between 100 and quality-control records. For some medicines,
conducts laboratory and animal studies to show 300, to see if it is effective, identify an optimal FDA requires additional trials (Phase IV) to
biological activity of the compound against the dose, and to further evaluate its short-term evaluate long-term effects.
targeted disease, and the compound is evalu- safety.
Discovering and developing safe and effective
ated for safety.
Clinical Trials, Phase III—The drug is given to a new medicines is a long, difficult, and expensive
Investigational New Drug Application (IND). larger, more diverse patient population, often process. PhRMA member companies invested an
After completing preclinical testing, a com- involving between 1,000 and 3,000 patients estimated $51.1 billion in research and develop-
pany files an IND with the U.S. Food and Drug (but sometime many more thousands), to gener- ment in 2013.
Administration (FDA) to begin to test the drug

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