Medicines in Development Neurological Disorders 2013

2013 R

EPORT

Neurological disorders—such as epi-lepsy, multiple sclerosis and Parkinson’s disease—inflict great pain and suffering on patients and their families, and every year costs the U.S. economy billions of dollars. Biopharmaceutical research companies are developing 444 new medicines to prevent and treat neu-rological disorders. The medicines in development are either in human clinical trials or under review at the Food and Drug Administration. They include:

• 82 medicines for Alzheimer’s disease, which afflicts more than 5 million Americans.

• 82 medicines for pain—100 million U.S. adults experience chronic pain.

• 62 medicines for brain tumors—nearly 70,000 Americans are diagnosed each year with a primary brain tumor.

• 38 medicines for multiple sclerosis, which afflicts an estimated 500,000 Americans.

• 28 medicines for epilepsy and sei-zures, which impact more than 3 million Americans.

• 27 medicines for Parkinson’s disease, which affects as many as 1 million Americans.

• 25 medicines for headache, includ-ing migraine, a condition that affects more than 37 million people.

Other medicines in development target amyotrophic lateral sclerosis (ALS), brain injuries, Huntington’s disease, spinal cord injury, cerebral palsy, and stroke. Among the many promising new medicines in development are:

• A medicine that prompts the immune system to protect neurons affected by ALS.

• Gene therapy for the treatment of Alzheimer’s disease.

• Gene therapy to reverse the effects of Parkinson’s disease.

The new medicines being developed by biopharmaceutical research companies reflect a growing understanding of the underlying mechanisms of neurological disorders, which fuels scientific progress and pharmaceutical research. These medi-cines offer patients hope that more effec-tive treatments may soon be available.

Biopharmaceutical Companies Researching and Developing Nearly 450 Medicines for Neurological Disorders

MeDiCiNes iN DevelopMeNt

Neurological DisordersA Report on Disorders of the Brain, spinal Cord and Nerves

presented by america’s biopharmaceutical research companies

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Medicines in Development For Neurological Disorders

Contents Key Issues ......................................2Disease Facts ..................................7Medicines in Development ...............11Glossary ...................................... 49Drug Development/ Approval Process ....................... 51

Medicines in Development neurological disorders 20132

innovative Medicines in the PipelineOf the 444 medicines in development in the United States listed in this report (see page 11), many present innovative new ways to target diseases. Some of them include:

• Gene Therapy to Restore Neuronal Function in Alzheimer’s—A gene therapy for the treatment of Alzheimer’s disease in clinical trials is designed to deliver nerve growth factor (NGF) to the brain. NGF is a naturally occurring protein important for neuron survival. The gene treatment is injected into the brain region where neuron degeneration occurs in Alzheimer’s disease. It is thought that the result-ing sustained expression of NGF in the neurons can restore their lost function, leading to memory and cognition improvement.

• Targeted RNAi Therapy Approach for Duchenne Muscular Dystrophy—In clinical trials, RNAi therapies have shown potential in treating neuromuscular dis-

orders such as Duchenne muscular dystrophy (DMD). In DMD, DNA deletions cause mutations in important genes that encode for dystrophin, a structural pro-tein found in normal muscle. The loss of this protein causes muscle fibers to disintegrate faster than they can be regenerated. One medicine in development targets restoration of dystrophin function and, as dys-trophin expression increases, there have been demon-strated improvements in patients’ ability to walk.

• Gene Therapy as a Possible Approach for Parkinson’s Disease—Inserting genes into cells can alter the im-pact the genes have on the proteins that are involved in a particular disease. These genes might alter or replace a mutated gene or produce a new thera-peutic protein entirely. In Parkinson’s disease, there are a number of treatments addressing the disease’s symptoms, but none that replace the lost nerve cells resulting from Parkinson’s or that would stop disease progression. More than one gene therapy in clinical trials uses an adeno-associated virus (AAV) as a vector

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Epilepsy

Genetic Disorders

Brain Tumors

Amyotrophic Lateral Sclerosis (ALS)

Brain Injury

Attention-Deficit/Hyperactivity Disorder

Alzheimer’s Disease

Parkinson’s Disease

Spasticity

Spinal Cord Injury

Stroke

33Other

Pain

Huntington’s Disease

Muscular Dystrophy

Multiple Sclerosis

Headache

Application Submitted

Phase III

Phase II

Phase I

Medicines in Development for Neurological Disorders By Disease and Phase

Some medicines are listed in more than one category

Medicines in Development neurological disorders 2013 3

to deliver neurturin to restore cells damaged in Parkinson’s patients and to protect them from fur-ther degeneration; these inactivated viruses pres-ent a safe way to get these important therapeutic options to patients.

• Als: Fighting a Devastating Disease—ALS, or Lou Gehrig’s disease, is a progressive neurode-generative disease that causes the brain to lose control over body movement, ultimately resulting in paralysis and death. The one drug approved to treat ALS can modestly slow progression of the disease, but new treatments are needed. As our scientific understanding of the disease has grown, researchers are pursuing many new approaches to halt or slow disease, including the use of the patient’s own bone marrow stem-cells to cre-ate healthy neuron-like cells to replace diseased neurons. Other trials are studying ways to prompt the immune system to protect neurons affected by ALS.

alzheimer’s: effective treatment is needed

Alzheimer’s is the 6th leading cause of death in the United States, and its impact on patients and the health care system is growing. Existing medicines are able to treat the symptoms of the disease but cannot slow, prevent, or reverse the progressive dementia. Disease-modifying treatments that could delay the onset of the disease could reduce the cost of care of Alzheimer’s patients in 2050 by $447 billion. Researchers continue to unravel the mysteries of the disease and are studying many new treatments in this area. Recent research has focused on the plaques and tangles which form in the brains of Alzheimer’s patients and are thought to contribute to the death of nerve cells. One medicine in development has shown promise in reducing both brain plaques and tangles. A gene therapy also in clinical trials is being explored to restore lost neuron function.

ALZHEIMER’S COSTS SOCIETY $203 BILLION AND COULD INCREASE TO $1.2 TRILLION BY 2050

ALZHEIMER’S COSTS SOCIETY $203 BILLION AND COULD INCREASE TO $1.2 TRILLION BY 2050

DELAYING DISEASE ONSET BY 5 YEARS COULD RESULT IN50% FEWER PATIENTS/SAVE $447 BILLION BY 2050DELAYING DISEASE ONSET BY 5 YEARS COULD RESULT IN50% FEWER PATIENTS/SAVE $447 BILLION BY 2050

ARE LIVING WITH ALZHEIMER’S DISEASEARE LIVING WITH ALZHEIMER’S DISEASE

BY 2050, THE NUMBER OF PATIENTS COULD TRIPLE WITHOUT EFFECTIVE TREATMENT

BY 2050, THE NUMBER OF PATIENTS COULD TRIPLE WITHOUT EFFECTIVE TREATMENT

5

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FEWERVICTIMS

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AMERICANS

2013

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+=

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AMERICANSMILLION15

IMPORTANCE TREATMENTALZHEIMER’SOF


Advancing Biomedical science Over the past decade, scientific advances and new technolo-gies have dramatically changed how medicines are discov-ered. This new information is critical to the development of new treatments for neurological disorders. Greater knowl-edge of how diseases work at the genetic and molecular level has allowed researchers to pursue new targets for therapy and better predict how certain biopharmaceuticals will affect specific subpopulations of patients.

• Bioinformatics—Bioinformatics use systems and mathematical models to advance the scientific un-derstanding of living systems. At its simplest level, bioinformatics involves the creation and maintenance of biological databases, including DNA sequences.

• Biomarkers—Every disease leaves a signature of molecular “biomarkers” in our body—genes that turn on and off or proteins released into the bloodstream. Biomarkers measured in blood and other samples can tell us the state of our health and how we might respond to treatment.

• Molecular Targeting—The idea behind molecular targeting is to design drugs that specifically attack the molecular pathways that cause disease without dis-rupting the normal functions in our cells and tissues.

• Nanotechnology—You can’t see it, but soon it will be everywhere. Nanotechnology is the science of build-ing microscopic devices at the molecular and atomic levels. In medicine, nanotechnology may also be used to help diagnose and treat diseases.

• Personalized Medicine—The sequencing of the human genome produced a “map” of the human genes in DNA. This new genetic knowledge opens up the possibility of developing “targeted” therapies for people with specific gene sequences, and it can help physicians choose the best treatments based on individual genetic, lifestyle, and environmental factors.

Breakthrough Research in Neurological DisordersEarly research discoveries often fuel the drug development pathways that biopharmaceutical company researchers un-dertake. These discoveries help researchers target a specific disease through certain mechanisms that may have been unknown before. Some noteworthy recent scientific discover-ies in the field of neurology include:

• Researchers at Mount Sinai Medical Center found 10 genes that account for half of the genetic risk for Alzheimer’s.

• Research at the National Institutes of Health found that a protein linked with some early-onset Parkin-son’s disease cases regulates how the body processes dietary fats. The study suggests there could be a link between the defective protein and early-onset Parkin-son’s disease.

• Scientists at the University of Chicago have uncovered a previously unknown process of protein production where a single gene can create two separate proteins from the same messenger RNA simultaneously. They believe this discovery will open the door for new research into therapies for neurological disorders.

• Research at the University of Missouri suggests that two identical neurons can reach the same electrical activity in different ways and could help doctors in treating patients with epilepsy.

• Two separate research groups have identified a muta-tion on the TREM2 gene that may increase a person’s chance of developing late-stage Alzheimer’s disease by three to five times.

• While studying at PennVet, a researcher discovered the gene responsible for Alexander disease, a rare, genetic neurological disorder where the white matter in the brain is destroyed and Rosenthal fibers form causing both mental and physical declines.


• At the University of Notre Dame, researchers have created a prodrug (an inactive drug that is converted into its active form once it’s in the body) of an inhibi-tor of the gelatinase enzyme. Gelatinase is associated with certain neurological disorders, such as strokes, aneurysms and traumatic brain injury.

• Researchers at the Manchester Institute of Biotech-nology in the United Kingdom have identified an enzyme in the brain that interacts with a compound for Huntington’s disease to inhibit its activity. Animal studies have shown that by switching off the enzyme’s activity through drug-binding, the enzyme is effec-tive in treating brain disorders such as Huntington’s, Alzheimer’s, and Parkinson’s.

the brain initiative

Brain Research through Advancing Innovative Neurotechnologies is a research effort launched by the Obama Administration to map the human brain and increase our understanding of how the human mind works. Approximately $100 million will be directed to government agencies, such as the National Institutes of Health, beginning in FY 2014. The BRAIN Initiative aims to accelerate the development and application of new technologies to help researchers understand the interworking’s of the brain, leading to new ways to treat and maybe one day prevent or cure diseases, such as Alzheimer’s, epilepsy and traumatic brain injury.

Public/Private Partnerships Critical to Advancing scienceCollaboration among partners in the entire medical innovation ecosystem is critical to help advance scientific understanding of some of the most complex diseases facing patients. Federal research institutions, academia, biopharmaceutical research companies and patient communities all play an important role in furthering research in the neurological field.

These evolving partnerships take many forms, for example:

• One biopharmaceutical company recently formed a research consortium to bring together several lead-ing academic research centers to coordinate their research and share results. Through this collaboration, researchers hope to accelerate their understanding of the disease and identify new approaches for targeting and treating amyotrophic lateral sclerosis (ALS).

• The Alzheimer’s Disease Neuroimaging Initiative is a collaborative effort between several federal agen-cies, non-profit organizations, and biopharmaceutical industry members. The goal of the Initiative is to track Alzheimer’s disease progression, establish quality stan-dards, and validate biomarkers to be used in clinical

trials. Data collected are made available at no cost to researchers when designing clinical trials and research projects.

• Another biopharmaceutical company is collaborating with a medical school’s neurodegenerative disease research center to screen for Alzheimer’s drug can-didates. The company is sharing their basic research with the research center’s screening assays and knowledge of the biology of the tau protein, which is thought to play a significant role in Alzheimer’s disease.

• The Coalition Against Major Diseases, a program of the Critical Path Institute, is a consortium of biophar-maceutical research companies, academic institu-tions, regulatory agencies, patient advocacy groups, research foundations, scientific associations and consultants that work collaboratively through a pre-competitive partnership to accelerate development of therapeutics for neurodegenerative diseases.


New Neurological Medicines Approved for PatientsThe new medicines being developed today build on the medical progress seen over the last decade or so. Below are exam-ples of innovative medicines approved recently to treat some neurological conditions.

Attention-Deficit/Hyperactivity Disorder (ADHD)

• vyvanse® (lisdexamphetamine dimesylate) is the first stimulant prodrug approved for the treatment of ADHD. It is an oral biologic medicine that is thera-peutically inactive until metabolized in the body. It is intended to provide a safer, abuse-resistant and effec-tive alternative to amphetamine-based therapies for ADHD.


• Namenda® (memantine) is the first treatment ap-proved for moderate to severe Alzheimer’s disease. It was also the first in a new class of medicines called NMDA receptor antagonists to be approved for the disease. Namenda interferes with the effects of excess glutamate release—glutamate plays a key role in the neural pathways associated with learning and memory.

Multiple Sclerosis (MS)

• Tecfidera™ (dimethyl fumarate; BG-12) is a first-line oral treatment for relapsing forms of MS. It is be-lieved to treat the disease in a new way by stimulating the Nrf2 transcriptional pathway that provides a way for cells in the body to defend against inflamma-tion and neuronal death that is induced by oxidative stress. In clinical trials it was shown to reduce relapses and the development of brain lesions, as well as slow disability progression.

• Gilenya® (fingolimod) is a first-in-class oral medicine also approved to treat relapsing forms of MS. With a different mechanism of action, it binds to the S1PR lipid and traps certain white blood cells in the lymph nodes, thereby reducing the immune system’s attack on the central nervous system (CNS). By preventing the blood cells from reaching the CNS where they can damage the covering around the nerve fibers, this medicine can reduce damage to the nerve cells.

Seizures

• Potiga® (ezogabine) is a first-in-class potassium chan-nel blocker approved for the adjunctive treatment of partial-onset seizures in adults. While the exact mech-anism of action is unknown, it is believed to work by opening the potassium channels, which are thought to stabilize the neurons and reduce brain excitability.


Brain Tumors4

Amyotrophic Lateral Sclerosis2

Brain Injury3

Alzheimer’s Disease and Other Dementias1

• An estimated 69,720 new cases of primary brain tumors (those that begin and tend to stay in the brain) are expected to be diagnosed in 2013, including both malignant (24,620) and non-malignant (45,100) brain tumors.

• In 2010, more than 688,096 people in the United States were living with the diagnosis of a primary brain or central ner-vous system tumor—more than 138,054 were malignant tumors and more than 550,042 were non-malignant.

• Gliomas, a broad term which includes all tumors arising from the gluey or supportive tissue of the brain, represent 30 percent of all brain tumors and 80 percent of all malignant tumors. Glioblastomas represent 17 percent of all primary brain tumors and 54 percent of all gliomas.

• An estimated 30,000 Americans may have amyotrophic lateral sclerosis (Als) at any given time, and some 5,600 people in the United States are diagnosed with ALS each year. It is estimated that ALS is responsible for nearly 2 deaths per 100,000 population annually.

• According to the U.S. Centers for Disease Control (CDC) Injury Prevention Center, the leading causes of traumatic brain in-jury (TBi) are: falls, 35.2 percent; unknown/other, 21 percent; motor vehicle, 17.3 percent; head strikes, 16.5 percent; assault, 10 percent.

• Traumatic brain injury is the leading cause of disability and death in children and adolescents in the United States. According to the CDC, the two age groups at greatest risk for TBI are ages 0-4 and 15-19. Among children ages 0 to 14 years, each year TBI results in an estimated: 2,685 deaths; 37,000 hospitalizations; and 435,000 emergency department visits.

• Approximately 1,300 U.S. children experience severe or fatal brain trauma from child abuse every year.

• An estimated 5.4 million Americans have Alzheimer’s disease (AD). Today, someone in America develops AD every 68 sec-onds. By 2050, there is expected to be one new case of AD every 33 seconds, or nearly a million new cases per year, and AD prevalence is projected to be 11 million to 16 million.

• AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 and older.

selected facts about neurological disorders


Epilepsy5

Headache

Huntington’s Disease9

Genetic Disorders6

• epilepsy affects nearly 3 million Americans. Epilepsy is the fourth most common neurological disorder in the United States after migraine, stroke, and Alzheimer’s disease. And it costs society $17.6 billion in direct and indirect costs.

• epilepsy strikes most often among the very young and the very old, although anyone can develop the disorder at any age. In this country, it affects more than 300,000 children under the age of 15—more than 90,000 of whom have seizures that cannot be adequately treated.

• The number of epilepsy cases in the elderly is climbing as the baby boom generation reaches retirement age. More than 300,000 adults age 65 and above have the condition.

• Headaches are the most prevalent neurological disorders and among the most frequent symptoms seen in general practice—50 percent of the general population have headaches during any given year, and more than 90 percent report a lifetime history of headache.7

• Chronic headache (a headache that occurs 15 or more days per month) affects 3 percent of the general population, and those people are the most severely disabled.7

• More than 37 million Americans suffer from migraine, with women being affected three times more often than men. This vascular headache is most commonly experienced between the ages of 15 and 55, and 70 percent to 80 percent of suffer-ers have a family history of migraine.8

• The financial cost of headache arises partly from direct treatment costs, but much more from loss of work time and produc-tivity. The annual U.S. direct medical costs attributable to migraine were estimated at $1 billion in 1999.7

• More than 15,000 Americans have Huntington’s disease (HD). At least 150,000 others have a 50 percent risk of develop-ing the disease, and thousands more of their relatives live with the possibility that they, too, might develop HD.

• More than 6,000 known genetic disorders account for a significant portion of human disease and conditions and can present themselves in several different ways, such as Down syndrome, spina bifida, and sickle cell anemia.

• Up to 4 percent of the approximately 4 millon babies born each year have a genetic disease or major birth defect. More than 20 percent of infant deaths are caused by birth defects or genetic conditions (e.g., congenital heart defects, abnormalities of the nervous system, or chromosomal abnormalities).

• Approximately 10 percent of all adults and 30 percent of children in hospitals are there due to genetically-related problems.




Spasticity15


Pain12

• spasticity is a common finding in multiple sclerosis (MS), stroke, traumatic brain injury (TBI), cerebral palsy (CP), and spinal cord injury (SCI). Within those patient populations, spasticity occurs at a variable rate. Studies have shown that spasticity affects between 37 percent and 78 percent of people with MS, 40 percent of those with SCI, approximately 35 percent of those with stroke, more than 90 percent with CP, and approximately 50 percent of patients with TBI.

• In the United States, 50,000-60,000 new cases of Parkinson’s disease (PD) are diagnosed each year, adding to the 1 million people who currently have PD. The U.S. Centers for Disease Control and Prevention rated complications from Parkinson’s disease as the 14th leading cause of death in the United States.13

• Men are one and a half times more likely to have Parkinson’s than women.14

• The combined direct and indirect costs of Parkinson’s, including treatment, Social Security payments and lost income from inability to work, is estimated to be nearly $25 billion per year in the United States. Medication costs for an individual person with PD average $2,500 a year, and therapeutic surgery can cost up to $100,000 dollars per patient.14

• In 2011, at least 100 million adult Americans had common chronic pain conditions.

• Recent Centers for Disease Control and Prevention (CDC) and National Center for Health Statistics (NCHS) data suggest sub-stantial rates of pain from various causes and that most people in chronic pain have multiple sites of pain. For U.S. adults report-ing pain, causes include: severe headache or migraine (16.1 percent), low back pain (28.1 percent), neck pain (15.1 percent), knee pain (19.5 percent), shoulder pain (9.0 percent), finger pain (7.6 percent), and hip pain (7.1 percent).

• Pain is a significant public health problem that costs society at least $560-$635 billion annually (an amount equal to about $2,000.00 for everyone living in the United States).

Muscular Dystrophy10

Multiple Sclerosis11

• The incidence rates of muscular dystrophies (MD) vary depending on the specific type. Duchenne MD is the most com-mon MD and is sex-linked, with an inheritance pattern of 1 case per 3,500 live male births. Becker MD is the second most common form, with an incidence of 1 case per 30,000 live male births. Other types of MD are rare. For example, limb-girdle dystrophy occurs in only 1.3 percent of patients with MDs.

• Some 350,000 to 500,000 patients suffer from multiple sclerosis (Ms) in the United States. Most cases are diagnosed between 20 and 50 years.



Sources:

1. Alzheimer’s Association, www.alz.org

2. ALS Association, www.alsa.org

3. Brain Injury Association of America, www.biausa.org

4. American Brain Tumor Association, www.abta.org

5. Epilepsy Foundation, www.epilepsyfoundation.org

6. NetWellness from Case Western Reserve University, Ohio State University and University of Cincinnati, www.netwellness.org

7. International Association for the Study of Pain, www.iasp-pain.org

8. National Headache Foundation, www.headaches.org

9. National Institute of Neurological Disorders and Stroke, www.ninds.nih.gov

10. E-Medicine, www.emedicine.medscape.com

11. Multiple Sclerosis Foundation, www.msfocus.org

12. The American Academy of Pain Medicine, www.painmed.org

13. National Parkinson Foundation, www.parkinson.org

14. Parkinson Disease Foundation, www.pdf.org

15. Medscape, www.medscape.org

16. National Spinal Cord Injury Statistical Center, www.nscisc.uab.edu

17. American Heart Association, www.heart.org/advocacy

Spinal Cord Injury16

Stroke17

• The estimated annual incidence of spinal cord injury (sCi), not including those who die at an accident scene, is approximate-ly 12,000 new cases each year. The estimated number of people living today with SCI ranges from 238,000 to 332,000.

• The costs for those living with sCi vary greatly according to injury severity. For example, the lifetime direct medical costs are more than $4.6 million for someone with high quadriplegia injured at age 25, compared with the more than $1.5 million it will cost someone injured at the same age who has incomplete motor functions.

• stroke is the nation’s fourth leading killer and a leading cause of long-term disability. Each year, about 795,000 people suf-fer a stroke. On average, someone in the United States has a stroke every 40 seconds, and every 4 minutes someone dies from one.

• Deaths from ischemic stroke, the most common type, are predicted to nearly double between 2000 and 2032. Conserva-tive estimates forecast that ischemic stroke alone will cost the United States $2.2 trillion from 2005 to 2050.

• The direct and indirect costs of stroke in the United States for 2009 were $38.6 billion, with an average per person expen-diture of $6,018.


medicines in development for neurological disorders

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


Product Name Sponsor Indication Development Phase*

AAB-003/PF-05236812(beta-amyloid protein inhibitor mAB)

Janssen Alzheimer ImmunotherapySouth San Francisco, CAPfizerNew York, NY

Alzheimer’s disease Phase Iwww.janssenrnd.comwww.pfizer.com

ABT-126(alpha-7-NNR antagonist)

AbbVieNorth Chicago, IL

Alzheimer’s disease Phase IIwww.abbvie.com

ABT-288(neurotransmitter receptor modulator)


Alzheimer’s disease Phase II completedwww.abbvie.com

ABT-384 AbbVieNorth Chicago, IL

Alzheimer’s disease(see also other)

Phase II completedwww.abbvie.com

ABT-957(calpain inhibitor)


Alzheimer’s disease Phase Iwww.abbvie.com

AC-1204(glucose stimulant)

Accera Broomfield, CO

mild to moderate Alzheimer’s disease Phase II/IIIwww.accerapharma.com

AD02 vaccine (amyloid-beta protein inhibitor)

AffirisVienna, AustriaGlaxoSmithKlineRsch. Triangle Park, NC

Alzheimer’s disease Phase IIwww.affiris.comwww.gsk.com

AD03 vaccine (amyloid-beta protein inhibitor)

AffirisVienna, AustriaGlaxoSmithKlineRsch. Triangle Park, NC

Alzheimer's disease Phase Iwww.affiris.comwww.gsk.com

APH-0703(protein kinase C stimulant)

Aphios CorporationWoburn, MA

Alzheimer’s disease Phase I/IIwww.aphios.com

ARC029(nilvadipine)

Archer PharmaceuticalsSarasota, FL

Alzheimer’s disease Phase I/IIwww.archerpharma.com

ARC031(soluble amyloid reducing/clearing agent)

Archer PharmaceuticalsSarasota, FL

Alzheimer’s disease Phase Iwww.archerpharma.com

ASP0777 Astellas Pharma USNorthbrook, IL

Alzheimer’s disease Phase Iwww.astellas.com




Product Name Sponsor Indication Development Phase

AVN 101(serotonin 5-HT6 receptor antagonist)

Avineuro PharmaceuticalsSan Diego, CA

Alzheimer’s disease Phase IIwww.avineuro.com

AVN 322(serotonin 6 receptor antagonist)

Avineuro PharmaceuticalsSan Diego, CA

Alzheimer’s disease Phase Iwww.avineuro.com

AVN 397 Avineuro PharmaceuticalsSan Diego, CA

Alzheimer’s disease Phase IIwww.avineuro.com

AVP-923(dextromethorphan/quinidine fixed-dose combination)

Avanir PharmaceuticalsAliso Viejo, CA

agitation in Alzheimer’s disease(see also pain)

Phase IIwww.avanir.com

AZD1446(alpha4/beta2 neuronal nicotinicreceptor agonist)

AstraZenecaWilmington, DETargaceptWinston-Salem, NC

Alzheimer’s disease Phase Iwww.astrazeneca.comwww.targacept.com

AZD2184(PET enhancer)

Navidea PharmaceuticalsDublin, OH

Alzheimer’s disease (diagnosis) Phase Iwww.navidea.com

AZD2995(PET enhancer)

Navidea PharmaceuticalsDublin, OH

Alzheimer’s disease (diagnosis) Phase Iwww.navidea.com

AZD3293(beta secretase)

Astex PharmaceuticalsDublin, CAAstraZenecaWilmington, DE

Alzheimer’s disease Phase Iwww.astx.comwww.astrazeneca.com

AZD5213(histamine-3 receptor antagonist)

AstraZenecaWilmington, DE

Alzheimer’s disease Phase IIwww.astrazeneca.com

BACE inhibitor Janssen PharmaceuticalsTitusville, NJShionogiFlorham Park, NJ

Alzheimer’s disease Phase Iwww.janssenpharmaceuticalsinc.comwww.shionogi.com

BAN2401(amyloid beta-protein inhibitor)

EisaiWoodcliff Lake, NJ

early stage Alzheimer’s disease Phase IIwww.eisai.com

BIIB037(human anti-amyloid beta mAb)

Biogen IdecWeston, MA

Alzheimer’s disease Phase Iwww.biogenidec.com

bisnorcymserine(BNC)

QR PharmaBerwyn, PA

Alzheimer’s disease Phase Iwww.qrpharma.com

BMS-241027(microtubule stabilizer)

Bristol-Myers SquibbPrinceton, NJ

Alzheimer’s disease Phase Iwww.bms.com




CAD106(amyloid beta-protein inhibitor)

Novartis PharmaceuticalsEast Hanover, NJ

Alzheimer’s disease Phase IIwww.novartis.com

CERE-110(AAV-NGF)

CeregeneSan Diego, CA

Alzheimer’s disease Phase IIwww.ceregene.com

crenezumab(anti-amyloid-beta mAb)

GenentechSouth San Francisco, CA

Alzheimer’s disease Phase IIwww.gene.com

davunetide intranasal Allon TherapeuticsVancouver, Canada

Alzheimer’s disease(see also Parkinson’s, other)

Phase IIwww.allontherapeutics.com

donepezil/memantine extended release(fixed-dose combination)

Adamas PharmaceuticalsEmeryville, CAForest LaboratoriesNew York, NY

moderate to severe Alzheimer’s disease

Phase IIwww.adamaspharma.comwww.frx.com

DSP-8658(PPAR alpha/gamma agonist)

Sunovion PharmaceuticalsMarlborough, MA

Alzheimer’s disease Phase Iwww.sunovion.com

E2212(amyloid precursor proteinsecretase modulator)


Alzheimer’s disease Phase I completedwww.eisai.com

E2609(BACE1 protein inhibitor)


Alzheimer’s disease Phase Iwww.eisai.com

ELND005 Speranza TherapeuticsDublin, Ireland

neuropsychiatric symptoms in Alzheimer’s disease(Fast Track)

Phase II

EVP-0962(gamma secretase modulator)

EnVivo PharmaceuticalsWatertown, MA

Alzheimer’s disease Phase IIwww.envivopharma.com

EVP-6124(alpha7 nicotinic acetylcholine receptor agonist)


Alzheimer’s disease Phase IIwww.envivopharma.com

Exebryl-1® amyloid-beta-protein/tau protein inhibitor

ProteoTechKirkland, WA

Alzheimer’s disease Phase Iwww.proteotech.com

F-18 T808(PET imaging)

Siemens Medical SolutionsMalvern, PA

Alzheimer’s disease (diagnosis) Phase 0www.usa.healthcare.siemens.com

F18-florbetaben(molecular imaging agent)

IBA MolecularDulles, VAPiramal HealthcareMumbai, India

Alzheimer’s disease (diagnosis) application submittedwww.iba-molecular.comwww.piramal.com





F18-flutemetamol(PET imaging agent)

GE HealthcareWaukesha, WI

Alzheimer’s disease (diagnosis) application submittedwww.gehealthcare.com

gantenerumab (RG1450)

RocheNutley, NJ

early stage Alzheimer’s disease Phase II/IIIwww.roche.com

GM6(peptide therapeutic)

Genervon BiopharmaceuticalsPasadena, CA

Alzheimer’s disease(see also amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s, spinal cord injury, stroke)

Phase Iwww.genervon.com

GSK2647544(Lp-PLA2 inhibitor)

GlaxoSmithKlineRsch. Triangle Park, NC

Alzheimer’s disease Phase Iwww.gsk.com

GSK2981710(medium chain triglycerides)


Alzheimer’s disease Phase Iwww.gsk.com

HPP-854(BACE1 inhibitor)

High Point PharmaceuticalsHigh Point, NC

Alzheimer’s disease Phase Iwww.highpointpharma.com

JNJ-54861911 Janssen Research & DevelopmentRaritan, NJ

Alzheimer’s disease Phase Iwww.janssenrnd.com

KU-046(amyloid beta-protein modulator)

Kareus TherapeuticsLa Chaux-de-Fonds, Switzerland

Alzheimer’s disease Phase Iwww.kareustherapeutics.com

LMTX(TRx-0238)

TauRx PharmaceuticalsSingapore

Alzheimer’s disease, frontotemporal dementia

Phase IIIwww.taurx.com

Lu AE58054(5-HT6 receptor antagonist)

LundbeckDeerfield, ILOtsuka America PharmaceuticalRockville, MD

Alzheimer’s disease (cognition) Phase IIwww.lundbeck.comwww.otsuka.com

LY2886721(beta secretase inhibitor)

Eli LillyIndianapolis, IN

Alzheimer’s disease(slow disease progression)

Phase Iwww.lilly.com

LY3002813(biological)


Alzheimer’s disease Phase Iwww.lilly.com

Lym Pro®

neurotrophic factor companion diagnostic

Amarantus BioSciencesSunnyvale, CA

Alzheimer’s disease (diagnosis) Phase IIwww.amarantus.com

MK-8931(BACE1 protein inhibitor)

MerckWhitehouse Station, NJ

Alzheimer’s disease Phase II/IIIwww.merck.com


Medicines in Development Neurological Disorders 2013 15



MSDC-0160(mTOT modulator insulin sensitizer)

Metabolic Solutions Development CompanyKalamazoo, MI

Alzheimer’s disease Phase IIwww.msdrx.com

NAV4694(fluorine-18 labeled precisionradiopharmaceutical)

Navidea BiopharmaceuticalsDublin, OH

Alzheimer’s disease (diagnosis) Phase IIwww.navidea.com

NAV5001(123I-labelled imaging agent)


dementia with Lewy bodies (diagnosis)(see also Parkinson’s)

Phase IIwww.navidea.com

NIC5-15(amyloid precursor proteinsecretase inhibitor)

HumaneticsMinneapolis, MN

Alzheimer’s disease Phase IIwww.humaneticscorp.com

PF-05212377(SAM-760)

PfizerNew York, NY

Alzheimer’s disease Phase IIwww.pfizer.com

pioglitazone companion diagnostic Takeda Pharmaceuticals U.S.A.Deerfield, ILZinfandel PharmaceuticalsChapel Hill, NC

Alzheimer’s disease (diagnosis) Phase Iwww.takeda.com

Posiphen®

R-phenserineQR PharmaBerwyn, PA

Alzheimer’s disease, mild cognitive impairment(see also Parkinson’s)

Phase IIwww.qrpharma.com

RG1577(MAO-B inhibitor)

RocheNutley, NJ

Alzheimer’s disease Phase IIwww.roche.com

RG7129(BACE1 protein inhibitor)

RocheNutley, NJ

Alzheimer’s disease Phase Iwww.roche.com

rilapladib(Lp-PLA2 inhibitor)


Alzheimer’s disease Phase IIwww.gsk.com

RVX-208(BET protein inhibitor)

ResverlogixCalgary, Canada

Alzheimer’s disease Phase Iwww.resverlogix.com

SAR110894(H3 antagonist)

Sanofi USBridgewater, NJ

Alzheimer’s disease Phase IIwww.sanofi.com

SAR228810(anti-protofibrillar AB mAb)


Alzheimer’s disease Phase Iwww.sanofi.com

SB742457(5HT6 antagonist)


Alzheimer’s disease Phase IIwww.gsk.com

Medicines in Development for Neurological Disorders

Medicines in Development Neurological Disorders 201316



sGC 1061(nomethiazole)

sGC PharmaWellesley, MA

Alzheimer’s disease Phase Iwww.sgcpharma.com

solanezumab (amyloid-beta protein inhibitor)


mild Alzheimer’s disease Phase IIIwww.lilly.com

ST101 Sonexa TherapeuticsSan Diego, CA

Alzheimer’s disease Phase IIwww.sonexa.com

T3D-959(dual PPAR agonist)

T3D TherapeuticsRsch. Triangle Park, NC

Alzheimer’s disease Phase I completedwww.t3dtherapeutics.com

T-817MA Toyama ChemicalTokyo, Japan

Alzheimer’s disease Phase IIwww.toyama-chemical.co.jp

TC-1734(ispronicline)

TargaceptWinston-Salem, NC

Alzheimer’s disease Phase IIwww.targacept.com

TC-5619 (alpha7nAChR)


Alzheimer’s disease Phase Iwww.targacept.com

TD-8954(5-HT4 agonist)


Alzheimer’s disease Phase Iwww.targacept.com

TTP488 Transtech PharmaHigh Point, NC

Alzheimer’s disease(Fast Track)

Phase IIwww.ttpharma.com

TTP4000 Transtech PharmaHigh Point, NC

Alzheimer’s disease Phase Iwww.ttpharma.com

V950 vaccine MerckWhitehouse Station, NJ

Alzheimer’s disease Phase Iwww.merck.com

vanutide cridificar(ACC-001/PF-05236806)

Janssen Alzheimer ImmunotherapySouth San Francisco, CAPfizerNew York, NY

Alzheimer’s disease Phase IIwww.janimm.comwww.pfizer.com

VI-1121 VIVUSMountain View, CA

Alzheimer’s disease Phase IIwww.vivus.com

XEL 001HP(transdermal patch)

Xel PharmaceuticalsDraper, UT

Alzheimer’s disease Phase Iwww.xelpharmaceuticals.com



Amyotrophic Lateral Sclerosis


arimoclomol(Orphan Drug)

ALS AssociationWashington, DCOrphazymeCopenhagen, DenmarkUniversity of MiamiMiami, FL

amyotrophic lateral sclerosis (ALS)(Fast Track)

Phase II/IIIwww.orphazyme.com



ALS (Fast Track) (see also Alzheimer’s, multiple sclerosis, Parkinson’s, spinal cord injury, stroke)

Phase IIwww.genervon.com

NP001(macrophage regulator)

Neuraltus PharmaceuticalsPalo Alto, CA

ALS Phase IIwww.neuraltus.com

NSI-566(stem cell therapy) (Orphan Drug)

NeuralstemRockville, MD

ALS Phase IIwww.neuralstem.com

NurOwn™GDNF-producing adult stem cell therapy(Orphan Drug)

BrainStorm Cell TherapeuticsNew York, NY

ALS Phase IIwww.brainstorm-cell.com

ozanezumab(NOGO-A mAb)


ALS Phase IIwww.gsk.com

stem cell therapy TCA Cellular TherapyCovington, LA

ALS(see also spinal cord injury)

Phase Iwww.tcacellulartherapy.com

tirasemtiv(Orphan Drug)

CytokineticsSouth San Francisco, CA

ALS (Fast Track)

Phase IIwww.cytokinetics.com



AR08(adrenergic receptor agonist)

Arbor PharmaceuticalsAtlanta, GA

attention-deficit/hyperactivity disorder (ADHD)

Phase IIwww.arborpharma.com

COL-171(sustained release)

Collegium PharmaceuticalsCumberland, RI

ADHD in clinical trialswww.collegiumpharma.com





d-amphetamine transdermal(ATS)

Noven PharmaceuticalsMiami, FL

ADHD Phase IIwww.noven.com

EB-1020(triple reuptake inhibitor)

Neurovance (Euthymics)Cambridge, MA

ADHD Phase Iwww.euthymics.com

edivoxetine(norepinephrine reuptake inhibitor)


ADHD (pediatric) Phase II/IIIwww.lilly.com

eltoprazine(serotonin 1A/1B partial agonist)

PsychoGenicsTarrytown, NY

ADHD (adults) Phase IIwww.psychogenics.com

HDL-100(amphetamine modified release)

Highland TherapeuticsToronto, Canada

ADHD Phase Iwww.highlandtherapeutics.com

HDL-200(methylphenidate modified-release)

Highland TherapeuticsToronto, Canada

ADHD Phase Iwww.highlandtherapeutics.com

KP106(d-amphetamine prodrug)

KemPharmNorth Liberty, IA

ADHD Phase I completedwww.kempharm.com

KRL-401 Krele Pharmaceuticals(TONIX Pharmaceuticals)New York, NY

ADHD in clinical trialswww.krele.com

methylphenidate extended release

Purdue PharmaStamford, CTRhodes PharmaCoventry, RI

ADHD Phase IIIwww.purduepharma.comwww.rhodespharma.com

NT0202(amphetamine controlled release)

Neos TherapeuticsGrand Prairie, TX

ADHD application submittedwww.neostx.com

NWP09(methylphenidate extended-release chewable tablets)

PfizerNew York, NY

ADHD Phase III completedwww.pfizer.com

OPC-34712(brexpiprazole)

LundbeckDeerfield, ILOtsuka America PharmaceuticalRockville, MD

ADHD (adults) Phase IIwww.lundbeck.comwww.otsuka.com





ORADUR®-ADHD(sustained-release oral gel)

DURECT Cupertino, CA

ADHD Phase Iwww.durect.com

SEP-225289(triple reuptake inhibitor)


ADHD Phase IIwww.sunovion.com

SPN-810(molindone)

Supernus PharmaceuticalsRockville, MD

impulsive aggression in ADHD (pediatric)

Phase II completedwww.supernus.com

SPN-812(norepinephrine uptake inhibitor)


ADHD Phase II completedwww.supernus.com

TD-9855(monoamine reuptake inhibitor)

TheravanceSouth San Francisco, CA

ADHD Phase IIwww.theravance.com

Brain Injury


BHR-100(intravenous progesterone infusion) (Orphan Drug)

BHR PharmaHerndon, VA

traumatic brain injury(Fast Track)

Phase IIIwww.bhr-pharma.com

ciclosporin intravenous (Orphan Drug)

Maas BiolabAlbuquerque, NMNeuroVive PharmaceuticalLund, Sweden

traumatic brain injury Phase Iwww.maasbiolab.comwww.neurovive.com

methamphetamine intravenous Sinapis PharmaJacksonville, FL

traumatic brain injury(see also stroke)

Phase I completedwww.sinapispharma.com

NNZ-2566(cytokine inhibitors/neuropeptide receptor modulator)

Neuren PharmaceuticalsBethesda, MD

traumatic brain injury(Fast Track)(see also other)

Phase IIwww.neurenpharma.com

NTx-428®

cell differentiation, nerve growth factor and stem cell stimulant

Stem Cell TherapeuticsToronto, Canada

traumatic brain injury Phase IIwww.stemcellthera.com

Oxycyte®

perfluorocarbon oxygen carrierOxygen BiotherapeuticsMorrisville, NC

traumatic brain injury Phase IIwww.oxybiomed.com



Brain Injury


RP-1127(glibenclamide)

Remedy PharmaceuticalsNew York, NY

moderate to severe traumatic brain injury(see also stroke)

Phase IIwww.remedypharmaceuticals.com

SAR127963(P75 receptor antagonist)


traumatic brain injury Phase Iwww.sanofi.com

Brain Tumors


8H9 mAb United TherapeuticsSilver Spring, MD

metastatic brain cancer Phase Iwww.unither.com

ABT-414(EGFR antagonist)


glioblastoma Phase Iwww.abbvie.com

AEE788(multiple tyrosine kinase inhibitor)


glioblastoma Phase I/IIwww.novartis.com

afatinib(ErbB tyrosine kinase inhibitor)

Boehringer Ingelheim PharmaceuticalsRidgefield, CT

glioblastoma Phase I/IIwww.boehringer-ingelheim.com

AMG 595(anti-EGFRvIII antibody-drug conjugate)

AmgenThousand Oaks, CA

anaplastic astrocytoma, glioblastoma

Phase Iwww.amgen.com

ANG1005(paclitaxel prodrug)

AngioChemMontreal, Canada

glioma Phase Iwww.angiochem.com

ARC 100(tubulin polymerisation inhibitor)

Archer BiosciencesNew York, NY

recurrent glioblastoma

--------------------------------------medulloblastoma, recurrent neuroblastoma

Phase IIwww.archerbiosciences.com-----------------------------------------Phase I/IIwww.archerbiosciences.com

AT-101(Bcl-2 inhibitor)

Ascenta TherapeuticsMalvern, PA

glioblastoma Phase IIwww.ascenta.com

Avastin®

bevacizumabGenentechSouth San Francisco, CA

first-line glioblastoma Phase IIIwww.gene.com

Azedra™iobenguane I-131(Orphan Drug)

Progenics PharmaceuticalsTarrytown, NY

neuroblastoma (pediatric) (Fast Track)

Phase IIwww.progenics.com



Brain Tumors


BKM120(PI3K inhibitor)


glioblastoma Phase Iwww.novartis.com

ch14.18 mAb(Orphan Drug)

United TherapeuticsSilver Spring, MD

neuroblastoma Phase IIIwww.unither.com

cilengitide(Orphan Drug)

EMD SeronoRockland, MA

glioblastoma Phase IIIwww.emdserono.com

cilengitide companion diagnostic EMD SeronoRockland, MAMDxHealthIrvine, CA

glioblastoma (diagnosis) Phase IIIwww.emdserono.comwww.mdxhealth.com

cintredekin besudotox(IL13-PE38QQR)(Orphan Drug)

INSYS TherapeuticsChandler, AZNational Institute of Neurological Disorders and StrokeBethesda, MD

glioma(Fast Track)

Phase Iwww.insysrx.com

CLR 1404 I-124(PET imaging)

Novelos TherapeuticsMadison, WI

brain tumor (diagnosis) Phase I/IIwww.novelos.com

Cotara®

(iodine-131 radiolabeled TNT mAb)(Orphan Drug)

Peregrine PharmaceuticalsTustin, CA

recurrent glioblastoma(Fast Track)

Phase IIwww.peregrineinc.com

crenolanib(receptor tyrosine kinase inhibitor) (Orphan Drug)

AROG PharmaceuticalsDallas, TX

glioma (pediatric) Phase Iwww.arogpharma.com

dacomitinib (PF-00299804)

PfizerNew York, NY

glioblastoma Phase IIwww.pfizer.com

DCVax®-Braindendritic cell vaccine(Orphan Drug)

Northwest BiotherapeuticsBethesda, MD

glioblastoma Phase IIIwww.nwbio.com

DNX-2401(cell death stimulant)

DNAtrixHouston, TX

glioblastoma Phase Iwww.dnatrix.com

E7080(lenvatinib)


glioma Phase IIwww.eisai.com



Brain Tumors


eflornithine(CPP-1X)

Cancer Prevention PharmaceuticalsTucson, AZ

neuroblastoma Phase IIwww.canprevent.com

ETS2101(synthetic terpene-based cannabinoid)

e-TherapeuticsOxfordshire, United KingdomUniversity of CaliforniaSan Diego, CA

glioma Phase Iwww.etherapeutics.co.uk

F18-ML-10(molecular imaging agent)

IBA MolecularDulles, VAAposensePetach-Tikva, Israel

brain tumors (diagnosis) Phase IIwww.iba-molecular.comwww.aposense.com

firtecan pegol(Orphan Drug)

Belrose PharmaPrinceton, NJ

neuroblastoma Phase I/IIwww.belrosepharma.com

galunisertib(LY2157299)


glioblastoma

--------------------------------------newly diagnosed glioma

Phase IIwww.lilly.com-----------------------------------------Phase I/IIwww.lilly.com

GDC-0084/RG7666(PI3K inhibitor)


glioma Phase Iwww.gene.com

GliAtak™cancer gene therapy (Orphan Drug)

AdvantageneAuburndale, MA

malignant glioma Phase IIwww.advantagene.com

Glionix™belagenpumatucel-Lsubcutaneous

NovaRx San Diego, CA

glioma Phase Iwww.novarx.com

Hiltonol® poly-ICLC(Orphan Drug)

OncovirWashington, DC

glioblastoma Phase II www.oncovir.com

ICT-107(autologous dendritic cell-based vaccine)(Orphan Drug)

ImmunoCellular TherapeuticsWoodland Hills, CA

glioblastoma Phase IIwww.imuc.com

IMA950(tumor-associated peptide vaccine)

Immatics BiotechnologiesTuebingen, Germany

glioblastoma Phase Iwww.immatics.com

LDE225(SMO protein inhibitor)


medulloblastoma Phase IIIwww.novartis.com



Brain Tumors


LEE011(cyclin-dependent kinase-4/6 inhibitor)


neuroblastoma Phase Iwww.novartis.com

macitentan Actelion PharmaceuticalsSouth San Francisco, CA

recurrent glioblastoma Phase Iwww.actelion.us

mibefradil Tau TherapeuticsCharlottesville, VA

recurrent glioma Phase Iwww.tautherapeutics.com

NEO100(perillyl alcohol intranasal) (Orphan Drug)

NEONC TechnologiesWoodland Hills, CA

glioblastoma in clinical trialswww.neonctech.com

neuroblastoma vaccine MabVaxSan Diego, CA

neuroblastoma Phase Iwww.mabvax.com

onartuzumab(anti-c-Met mAb)


recurrent glioblastoma Phase IIwww.gene.com

Opaxio®

paclitaxel poliglumex(Orphan Drug)

Cell TherapeuticsSeattle, WA

glioblastoma Phase IIwww.celltherapeutics.com

palbociclib(PD-0332991/CDK4-6 kinase inhibitor)

PfizerNew York, NY

Rb-positive glioblastoma Phase IIwww.pfizer.com

perifosine AEterna Zentaris Basking Ridge, NJ

glioma Phase IIwww.aezsinc.com

PLX3397 PlexxikonBerkeley, CA

glioblastoma Phase IIwww.plexxikon.com

PX-866(PI-3 kinase inhibitor)

OncothyreonSeattle, WA

glioblastoma Phase IIwww.oncothyreon.com

Reolysin®

pelareorepOncolytics BiotechCalgary, Canada

glioma Phase I/II completedwww.oncolyticsbiotech.com

rindopepimut(EGFR varient III vaccine) (Orphan Drug)

Celldex TherapeuticsNeedham, MA

first-line glioblastoma (Fast Track)--------------------------------------recurrent glioblastoma (Fast Track)

Phase IIIwww.celldextherapeutics.com-----------------------------------------Phase IIwww.celldextheraputics.com

SB-313(T-cell receptor gene stimulant)

Sangamo BiosciencesRichmond, CACity of Hope National Medical CenterDuarte, CA

glioblastoma Phase Iwww.sangamo.com



Brain Tumors


SL-701 (dendritic cell vaccine)

Stemline TherapeuticsNew York, NY

glioma Phase I/IIwww.stemline.com

Tarceva®

erlotinibAstellas Pharma USNorthbrook, IL

recurrent ependymoma (pediatric) Phase IIIwww.astellas.com

terameprocol(intravenous)

Erimos PharmaceuticalsRaleigh, NC

glioma Phase I/IIwww.erimos.com

Toca 511/Toca FC(fluorouracil prodrug gene therapy)

TocagenSan Diego, CA

recurrent glioblastoma

--------------------------------------late-stage glioma

Phase I/IIwww.tocagen.com-----------------------------------------Phase Iwww.tocagen.com

TRC105(ENG protein inhibitor)

Tracon PharmaceuticalsSan Diego, CA

glioblastoma Phase IIwww.traconpharma.com

TSC(trans-sodium crocetinate)

Diffusion PharmaceuticalsCharlottesville, VA

glioblastoma Phase I/IIwww.diffusionpharma.com

TVI-Brain-1(cancer vaccine)

TVAX BiomedicalLenexa, KS

glioma Phase IIwww.tvaxbiomedical.com

Tykerb®

lapatinibGlaxoSmithKlineRsch. Triangle Park, NCJonsson Comprehensive Cancer CenterLos Angeles, CA

glioblastoma Phase IIwww.gsk.com

VAL-083 (Orphan Drug)

Del Mar PharmaceuticalsVancouver, Canada

glioblastoma Phase I/IIwww.delmarpharma.com

VB-111(gene therapy)

VBL TherapeuticsOr Yehuda, Israel

glioblastoma Phase I/IIwww.vblrx.com

veliparib AbbVieNorth Chicago, IL

brain metastases Phase IIwww.abbvie.com

vemurafenib RocheNutley, NJ

brain metastases Phase IIwww.roche.com

vitespen(G-100 prophage)

AgenusLexington, MA

glioma Phase IIwww.agenusbio.com

Xeloda®

capecitabineRocheNutley, NJ

glioma (pediatric) Phase IIwww.roche.com



Epilepsy


Banzel®rufinamide (Orphan Drug)


Lennox-Gastaut syndrome (pediatric) Phase IIIwww.eisai.com

BGG492(selurampanel)


partial seizures(see also headache)

Phase II completedwww.novartis.com

brivaracetam UCBSmyrna, GA

epilepsy Phase IIIwww.ucb.com

CPP -15(GABA-aminotransferase inhibitor)(Orphan Drug)

Catalyst Pharmaceutical PartnersCoral Gables, FL

complex partial seizures, infantile spasms

Phase Iwww.catalystpharma.com

diazepam intranasal spray(Orphan Drug)

Acorda TherapeuticsArdsley, NY

acute repetitive seizures Phase IIIwww.acorda.com

DSP-0565(sodium/calcium channel blocker)

Sunovion Pharmaceuticals Marlborough, MA

epilepsy Phase Iwww.sunovion.com

ezogabine extended release GlaxoSmithKlineRsch. Triangle Park, NCValeant Pharmaceuticals North AmericaBridgewater, NJ

partial onset seizures Phase IIIwww.gsk.comwww.valeant.com

Fycompa®

perampanelEisaiWoodcliff Lake, NJ

generalized seizures

--------------------------------------partial-onset seizures (pediatric)

Phase IIIwww.eisai.com-----------------------------------------Phase IIwww.eisai.com

ganaxolone (Orphan Drug)

Marinus PharmaceuticalsNew Haven, CT

infantile spasms (infants),partial-onset seizures (adults)

Phase IIwww.marinuspharma.com

INS-001(huperzine A)

Insero HealthMiami, FL

epilepsy Phase Iwww.insero.com

I.V. carbamazepine LundbeckDeerfield, IL

epilepsy Phase IIIwww.lundbeck.com

JZP8(clonazepam intranasal)

Jazz PharmaceuticalsPalo Alto, CA

recurrent acute repetitive seizures Phase IIwww.jazzpharma.com

Lyrica®

pregabalinPfizerNew York, NY

generalized tonic clonic seizures(see also pain)

Phase IIIwww.pfizer.com

midazolam intranasal(USL261)

Upsher-Smith LaboratoriesMaple Grove, MN

acute repetitive seizures(Fast Track)

Phase IIIwww.upsher-smith.com



Epilepsy


naluzotan(serotonin 1A receptor agonist/sigma-1 receptor antagonist)

ProximagenLondon, United Kingdom

epilepsy Phase IIwww.proximagen.com

NRL-1(diazepam intranasal)

Biotie TherapiesTurku, Finland NeuralisSan Diego, CA

epilepsy Phase I www.biotie.com

PF-04895162 PfizerNew York, NY

epilepsy Phase I completedwww.pfizer.com

Potiga™ezogabine

GlaxoSmithKlineRsch. Triangle Park, NCValeant Pharmaceuticals North AmericaBridgewater, NJ

Lennox-Gastaut syndrome, partial onset seizures(patients age 12 and older)

Phase IIIwww.gsk.comwww.valeant.com

pregabalin controlled release PfizerNew York, NY

epilepsy (adjunctive treatment)(see also pain)


Stedesa®

eslicarbazepine acetateSunovion PharmaceuticalsMarlborough, MA

partial seizures in adults(adjunctive therapy)--------------------------------------partial seizures (monotherapy)

application submittedwww.sunovion.com-----------------------------------------Phase IIIwww.sunovion.com

tonabersat(USL260)

Upsher-Smith LaboratoriesMaple Grove, MN

epilepsy Phase Iwww.upsher-smith.com

topiramate extended release(USL255)

Upsher-Smith Laboratories Maple Grove, MN

partial-onset seizures application submittedwww.upsher-smith.com

topiramate intravenous(Captisol®-enabled)

CyDex Pharmaceuticals(Ligand Pharmaceuticals)Lenexa, KS

epilepsy Phase Iwww.ligand.com

Trokendi XR™topiramate controlled release


epilepsy application submittedwww.supernus.com

Vanquix® Auto-Injectordiazepam injection

PfizerNew York, NY

acute repetitive seizures(intermittent therapy)


Vimpat®

lacosamideUCBSmyrna, GA

epilepsy (monotherapy)

--------------------------------------epilepsy in patients 2-17 years of age (adjunctive therapy), primary gener-alized tonic clonic seizures (adjunctive therapy)

Phase IIIwww.ucb.com-----------------------------------------Phase IIwww.ucb.com



Epilepsy


VX-765(caspase 1 inhibitor)

Vertex PharmaceuticalsCambridge, MA

treatment-resistant partial epilepsy Phase IIwww.vrtx.com

YKP-3089 SK biopharmaceuticalsFair Lawn, NJ

epilepsy(see also pain)

Phase IIwww.skbp.com

Genetic Disorders


Afinitor®

everlimusNovartis PharmaceuticalsEast Hanover, NJ

seizures associated with tuberoussclerosis complex (TSC)

Phase IIIwww.novartis.com

deferiprone ApoPharmaToronto, Canada

pantothenate kinase-associated neurodegeneration

Phase IIIwww.apotex.com

ecopipam(D1 dopamine receptor antagonist)(Orphan Drug)

Psyadon PharmaceuticalsGermantown, MD

Lesch-Nyhan syndrome(see also other)

Phase IIIwww.psyadonrx.com

Gammagard Liquid™immune globulin

Baxter HealthcareDeerfield, IL

Friedreich’s ataxia Phase IIwww.baxter.com

HuCNS-SC® adult neural stem cell therapy

StemCellsNewark, CA

Pelizaeus-Merzbacher disease(see also spinal cord injury)

Phase Iwww.stemcellsinc.com

ISIS-SMNRx(antisense oligonucleotide)(Orphan Drug)

Biogen IdecWeston, MA Isis PharmaceuticalsCarlsbad, CA

spinal muscular atrophy(Fast Track)

Phase IIwww.biogenidec.comwww.isispharm.com

ISIS-TTRRx(antisense RNA modulator)(Orphan Drug)

Isis PharmaceuticalsCarlsbad, CA

familial amyloid polyneuropathy(Fast Track)

Phase II/IIIwww.isispharm.com

Lenti-D™adrenoleukodystrophy gene therapy(Orphan Drug)

Bluebird BioCambridge, MA

childhood cerebral adrenoleukodystrophy

Phase I/IIwww.bluebirdbio.com

PF-06687859(DcpS protein inhibitor) (Orphan Drug)

PfizerNew York, NY

spinal muscular atrophy Phase Iwww.pfizer.com

RG2833(HDAC inhibitor) (Orphan Drug)

RepligenWaltham, MA

Friedreich’s ataxia Phase I completedwww.repligen.com



Genetic Disorders


tafamidis meglumine(transthyretin dissociation inhibitor)(Orphan Drug)

PfizerNew York, NY

transthyretin familial amyloid poly-neuropathy(Fast Track)

application submittedwww.pfizer.com

vatiquinone(EPI-743)(Orphan Drug)

Edison PharmaceuticalsMountain View, CA

mitochondrial myopathies

--------------------------------------Friedreich’s ataxia, Leigh’s disease

Phase II/IIIwww.edisonpharma.com-----------------------------------------Phase IIwww.edisonpharma.com

VP20629 ViroPharmaExton, PA

Friedreich’s ataxia Phase Iwww.viropharma.com

UX001 sialic acid(sialic acid extended release)

Ultragenyx PharmaceuticalsNovato, CA

hereditary inclusion body myositis Phase IIwww.ultragenyx.com

Headache


ALD403(CGRP inhibitor mAb)

Alder BiopharmaceuticalsBothell, WA

prevention of migraine (subcutaneous)--------------------------------------prevention of migraine(intravenous)

Phase IIwww.alderbio.com-----------------------------------------Phase Iwww.alderbio.com

AMG 334(CGRP receptor antagonist mAb)

AmgenThousand Oaks, CA

migraine Phase Iwww.amgen.com

Amrix®

cyclobenzaprine extended releaseCephalon (Teva)Frazer, PA

migraine Phase IIIwww.tevapharm.com

AP-1531 (EPH receptor antagonist)

Ariel PharmaceuticalsBroomfield, CO

migraine Phase I

AVP-825 (sumatriptan intranasal)

Avanir Pharmaceuticals Aliso Viejo, CA

migraine Phase IIIwww.avanir.com

AZ-104(Staccato® loxapine low dose)

Alexza PharmaceuticalsMountain View, CA

migraine Phase II completedwww.alexza.com



Headache


BGG492(selurampanel)


migraine(see also epilepsy)

Phase IIwww.novartis.com

Botox®

onabotulinumtoxinAAllerganIrvine, CA

prevention of migraine (adolescents)(see also pain, other)

Phase IIIwww.allergan.com

CL-H1T(sumatriptan)

Charleston LaboratoriesCharleston, SC

migraine Phase IIwww.charlestonlabs.com

doxepin intranasal Winston PharmaceuticalsVernon Hills, IL

chronic daily headache Phase IIwww.winstonlabs.com

DR-105(ethinylestradiol/levonorgestrel)

Duramed Pharmaceuticals (Teva)North Wales, PA

menstrual migraine Phase II completedwww.tevapharm.com

lasmiditan(serotonin 1F receptor agonist)

CoLucid PharmaceuticalsDurham, NC

migraine Phase IIwww.colucid.com

LBR-101(CGRP mAb)

Labrys BiologicsSan Mateo, CA

prevention of chronic migraine Phase Iwww.labrysbiologics.com

Levadex®

dihydroergotamine mesilateinhalation

AllerganIrvine, CAMAP PharmaceuticalsMountain View, CA

migraine (adults) application submittedwww.allergan.com

LY2951742(calcitonin gene-related peptideantagonist mAb)

Arteaus TherapeuticsCambridge, MAEli LillyIndianapolis, IN

prevention of migraine Phase IIwww.arteaus.comwww.lilly.com

NVD-201(sumatriptan oral spray)

NovaDelBridgewater, NJ

migraine Phase IIwww.novadel.com

NXN-188(nNOS inhibitor/5-HT agonist)

NeurAxonMississauga, Canada

acute migraine Phase II completedwww.neuraxon.com

odansetron/rizatriptanfixed-dose combination

MonoSol RxWarren, NJ

migraine Phase Iwww.monosolrx.com

rizatriptan oral film IntelGenxVille St-Laurent, CanadaRedHill BiopharmaTel Aviv, Israel

migraine application submittedwww.intelgenx.comwww.redhillbio.com

RT001(botulinum toxin A topical)

Revance TherapeuticsNewark, CA

migraine Phase IIwww.revance.com



Headache


SPRIX®

ketorolac intranasalRegency TherapeuticsShirley, NY

migraine Phase IIIwww.regencytherapeutics.com

TI-001(oxytocin intranasal)

TrigeminaMoraga, CA

chronic migraine, daily headache Phase IIwww.trigemina.com

ubrogepant(MK-1602)


migraine Phase IIwww.merck.com

zolmitriptan intranasal Shin Nippon Biomedical Laboratories USAEverett, WA

migraine Phase Iwww.snblusa.com

zucapsaicin(TRPV-1 agonist)

Winston PharmaceuticalsVernon Hills, IL

cluster headache(see also pain)

Phase IIIwww.winstonlabs.com

Huntington’s Disease


EX-527(SIRT1 protein inhibitor)

Siena BiotechSiena, Italy

Huntington’s disease Phase I completedwww.sienabiotech.com

GSK356278(PDE4 inhibitor)


Huntington’s disease Phase Iwww.gsk.com

OMS-824(PDE10 inhibitor)

OmerosSeattle, WA

Huntington’s disease Phase Iwww.omeros.com

PBT2(metal protein-attenuating compound)

Prana BiotechnologyParkville, Australia

Huntington’s disease Phase IIwww.pranabio.com

pridopidine (Orphan Drug)

Teva PharmaceuticalNorth Wales, PA

Huntington’s disease Phase IIIwww.tevapharm.com

RP103(mercaptamine bitartratedelayed release)

Raptor PharmaceuticalsNovato, CA

Huntington’s disease Phase II/IIIwww.raptorpharma.com

SD-809(VMAT inhibitor)

Auspex PharmaceuticalsLa Jolla, CA

Huntington’s disease(see also other)

Phase Iwww.auspexpharma.com



Multiple Sclerosis


ABT-413(sphingosine-1 phosphate receptor modulator)


multiple sclerosis Phase Iwww.abbvie.com

anti-LINGO(LINGO-1-protein-inhibitor)


multiple sclerosis Phase IIwww.biogenidec.com

ARX424(peginterferon beta-1a)

AmbrxLa Jolla, CA

multiple sclerosis Phase Iwww.ambrx.com

ATX-MS-1467(immune tolerizing agent)


multiple sclerosis Phase Iwww.emdserono.com

AZ01(peginterferon beta)

AllozyneSeattle, WA

multiple sclerosis Phase Iwww.allozyne.com

BHT-3009 (DNA vaccine)

Bayhill TherapeuticsPalo Alto, CA

relapsing-remittingmultiple sclerosis

Phase II completedwww.bayhilltx.com

Copaxone®glatiramer acetate for injection(20 mg)

Teva PharmaceuticalNorth Wales, PA

multiple sclerosis application submittedwww.tevapharm.com

daclizumab AbbVieNorth Chicago, ILBiogen IdecWeston, MA

multiple sclerosis, relapsing forms Phase IIIwww.abbvie.comwww.biogenidec.com

firategrast(dual alpha4-integrin antagonist)


multiple sclerosis Phase IIwww.gsk.com

GEH-120714(18F-labeled imaging agent)

GE HealthcareWaukesha, WI

multiple sclerosis (diagnosis) Phase Iwww.gehealthcare.com



multiple sclerosis(see also Alzheimer’s, amyotrophic lateral sclerosis, Parkinson’s, spinal cord injury, stroke)


GSK239512(H3 receptor inhibitor)


multiple sclerosis Phase IIwww.gsk.com

GSK2618960(IL-7 modulator mAb)


multiple sclerosis Phase Iwww.gsk.com

idebenone Santhera PharmaceuticalsLiestal, SwitzerlandU.S. National Institutes of HealthBethesda, MD

primary progressive multiple sclerosis(see also other)

Phase I/IIwww.santhera.com



Multiple Sclerosis


imilecleucel-T Opexa TherapeuticsThe Woodlands, TX

secondary progressive multiple sclerosis(Fast Track)

Phase IIwww.opexatherapeutics.com

IR208(immunostimulant vaccine)

Immune Response BioPharmaNew York, NY

multiple sclerosis Phase IIwww.immuneresponsebiopharma.com

laquinimod Teva PharmaceuticalNorth Wales, PA

multiple sclerosis(Fast Track)

Phase IIIwww.tevapharm.com

Lemtrada™alemtuzumab

Bayer HealthCare PharmaceuticalsWayne, NJGenzymeCambridge, MA

multiple sclerosis (Fast Track)

application submittedwww.bayerpharma.comwww.genzyme.com

masitinib AB Science USAShort Hills, NJ

multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis

Phase II/IIIwww.ab-science.com

MEDI-551(anti-CD19 mAb)

MedImmuneGaithersburg, MD

multiple sclerosis Phase Iwww.medimmune.com

MOR103(GM-CSF antagonist mAb)


multiple sclerosis Phase I/II completedwww.gsk.com

ocrelizumab(humanized anti-CD20 mAb)

Biogen IdecWeston, MAGenentechSouth San Francisco, CA

primary progressive multiple sclerosis, relapsing-remitting multiple sclerosis

Phase IIIwww.biogenidec.comwww.gene.com

ofatumumabsubcutaneous(CD20 human mAb)

Genmab USPrinceton, NJGlaxoSmithKlineRsch. Triangle Park, NC

relapsing-remitting multiple sclerosis Phase IIwww.genmab.comwww.gsk.com

ONO-4641(oral S1P receptor modulator)


multiple sclerosis Phase IIwww.emdserono.com

Plegridy™peginterferon beta-1a


multiple sclerosis, relapsing forms(Fast Track)

application submittedwww.biogenidec.com

plovamer acetate(second-generation peptide copolymer)


multiple sclerosis Phase Iwww.emdserono.com



Multiple Sclerosis


ponesimod Actelion PharmaceuticalsSouth San Francisco, CA

multiple sclerosis Phase II completedwww.actelion.com

rHIgM22(myelin protein stimulant mAb)


multiple sclerosis Phase Iwww.acorda.com

RPC1063(S1P1 receptor agonist)

ReceptosSan Diego, CA

relapsing multiple sclerosis Phase II/IIIwww.receptos.com

RTL1000 (T-lymphocyte modulator)

Artielle ImmunoTherapeuticsSan Mateo, CA

multiple sclerosis Phase Iwww.artielle.com

Sativex®

nabiximolsGW PharmaceuticalWiltshire, United Kingdom

muscle spasticity in multiple sclerosis Phase IIwww.gwpharm.com

secukinumab(AIN457)


multiple sclerosis Phase IIwww.novartis.com

siponimod(BAF312)


multiple sclerosis Phase IIIwww.novartis.com

Trimesta™estriol succinate

Synthetic BiologicsRockville, MD

multiple sclerosis Phase IIwww.syntheticbiologics.com

TSO(trichuris suis ova/CNDO-201)

Coronado BiosciencesBurlington, MA

multiple sclerosis Phase IIwww.coronadobiosciences.com

Tysarbi®natalizumab


multiple sclerosis (first-line therapy) in patients negative for JCV antibodies--------------------------------------secondary-progressive multiple sclerosis

application submittedwww.biogenidec.com-----------------------------------------Phase IIIwww.biogenidec.com

VX15 (SEMA-4D mAb)

Teva Pharmaceutical North Wales, PA VaccinexRochester, NY

multiple sclerosis Phase Iwww.tevapharm.comwww.vaccinex.com

XP23829(NF-kappa B inhibitor)

XenoportSanta Clara, CA

multiple sclerosis Phase Iwww.xenoport.com



Muscular Dystrophy


AAV1-FS344(gene therapy-delivered myostatin inhibitor)(Orphan Drug)

Milo BiotechnologyCleveland, OH

Duchenne muscular dystrophy Phase I/IIwww.milobiotechnology.com

ataluren (Orphan Drug)

PTC TherapeuticsSouth Plainfield, NJ

Duchenne muscular dystrophy(Fast Track)

Phase IIIwww.ptcbio.com

drisapersen(antisense oligonucleotide) (Orphan Drug)

GlaxoSmithKlineRsch. Triangle Park, NCProsensaLeiden, Netherlands

Duchenne muscular dystrophy Phase IIIwww.gsk.com

eteplirsen(RNA interference)

Sarepta TherapeuticsCambridge, MA

Duchenne muscular dystrophy(Fast Track)

Phase IIwww.sareptatherapeutics.com

GNE lipoplex(muscular dystrophy gene therapy)

GradalisCarrollton, TX

hereditary inclusion body myopathy

Phase Iwww.gradalisinc.com

HT-100(halofunginone)(Orphan Drug)

Halo TherapeuticsNewton, MA

Duchenne muscular dystrophy Phase I/IIwww.halotherapeutics.com


muscular dystrophy Phase Iwww.pfizer.com

Pain


ABT-639(T-type calcium channel antagonist)


diabetic neuropathy Phase IIwww.abbvie.com

ABT-652(histamine H3 receptor modulator)


diabetic neuropathy Phase IIwww.abbvie.com

AF-219(purinergic P2 receptor antagonist)

Afferent PharmaceuticalsSan Mateo, CA

osteoarthritis pain Phase IIwww.afferentpharma.com

agomelatine (NRT-31/36)

NectidPrinceton, NJ

neuropathic pain, painassociated with multiple sclerosis

Phase IIwww.nectid.com



Pain


ALO-02(oxycodone/naltrexone core/abuse resistant)

PfizerNew York, NY

moderate to severe chronic pain Phase IIIwww.pfizer.com

AmiKet™amitriptyline/ketamine

EpiCeptTarrytown, NY

neuropathic pain(Fast Track)

Phase IIwww.epicept.com

ARA 290(erythropoietin receptor agonist)

Araim PharmaceuticalsYorktown, NY

diabetic neuropathy Phase IIwww.araim.org

ARC-2022(lidocaine topical gel)

Arcion TherapeuticsBaltimore, MD

postherpetic neuralgia Phase I/IIwww.arciontherapeutics.com

ARRY-797(p38 MAP kinase inhibitor)

Array BioPharmaBoulder, CO

osteoarthritis pain Phase IIwww.arraybiopharma.com

AS-3201 (ranirestat)


diabetic neuropathy Phase IIIwww.eisai.com

ATx08 001(PPAR-gamma agonist)

Aestus TherapeuticsEast Windsor, NJ

postherpetic neuralgia Phase IIwww.aestustherapeutics.com

AV-101(NMDA receptor antagonist)

VistaGen TherapeuticsSouth San Francisco, CA

neuropathic pain Phase Iwww.vistagen.com

AVP-786(deuterated dextromethorphan)


chronic pain Phase Iwww.avanir.com

AVP-923(dextromethorphan/quinidine fixed-dose combination)


diabetic neuropathy(see also Alzheimer’s)--------------------------------------central neuropathic pain in multiple sclerosis

Phase IIIwww.avanir.com-----------------------------------------Phase IIIwww.avanir.com

BEMA buprenorphine transmucosal BioDelivery Sciences InternationalRaleigh, NC

neuropathic pain Phase IIIwww.bdsi.com

Botox®


osteoarthritis pain(see also headache, other)

Phase IIwww.allergan.com

Butrans™ Transdermal System CIIIbuprenorphine transdermal

Purdue PharmaStamford, CT

chronic pain (adolescents) Phase IIIwww.purduepharma.com

Celebrex®

celecoxibPfizerNew York, NY

chronic pain application submittedwww.pfizer.com



Pain


clonidine topical gel BioDelivery SciencesRaleigh, NC

diabetic neuropathy(Fast Track)

Phase IIwww.bdsi.com

CNSB015(flupirtine-based pain therapy)

Relevare PharmaceuticalsMelbourne, Australia

neuropathic pain Phase I/IIwww.relevarepharma.com

COL-003(oxycodone extended release/abuse-resistant formulation)

Collegium PharmaceuticalsCanton, MA

chronic lower back pain Phase IIIwww.collegiumpharma.com

COL-172(oxymorphone extended release/abuse resistant)

Collegium PharmaceuticalsCanton, MA

chronic lower back pain(Fast Track)

Phase Iwww.collegiumpharma.com

C-peptide long-acting(CBX129801)

CebixLa Jolla, CA

diabetic neuropathy (Fast Track)

Phase IIwww.cebix.com

CR845(opioid kappa receptor agonist)

Cara TherapeuticsShelton, CT

chronic pain Phase Iwww.caratherapeutics.com

CTP-354(GABA-A receptor modulator)

Concert PharmaceuticalsLexington, MA

neuropathic pain(see also spasticity)

Phase Iwww.concertpharma.com

diclofenac nano-formulation Iroko PharmaceuticalsPhiladelphia, PA

osteoarthritis pain Phase IIIwww.iroko.com

DS-5565(CACNA2D1 protein modulator)

Daiichi SankyoParsippany, NJ

chronic pain Phase IIwww.dsi.com

Eladur®

bupivacaine transdermal(Orphan Drug)

DURECTCupertino, CA

post-herpetic neuralgia Phase IIwww.durect.com

ELI-154(oxycodone controlled release)

Elite PharmaceuticalsNorthvale, NJ

chronic pain Phase IIwww.elitepharma.com

ELI-216(oxycodone/naltrexonefixed-dose combination)

Elite PharmaceuticalsNorthvale, NJ

moderate to severe chronic pain Phase IIwww.elitepharma.com

EMA401(angiotensin-type-2 receptor antagonist)

Spinifex PharmaceuticalsSouth Yarra, Australia

postherpetic neuralgia Phase Iwww.spinifexpharma.com.au

Fentora®

fentanyl buccalCephalon (Teva)Frazer, PA

chronic pain application submittedwww.tevapharm.com



Pain


filorexant(dual orexin receptor antagonist)


diabetic neuropathy Phase IIwww.merck.com

fulranumab(nerve growth factor inhibitor)

Janssen Research & DevelopmentRaritan, NJ

neuropathic pain Phase IIwww.janssenrnd.com

GRT6005(ORL-1 receptor agonist)

Forest LaboratoriesNew York, NY

pain due to osteoarthritis of the knee Phase IIwww.frx.com

hydrocodone extended release (CEP-33237)

Cephalon (Teva)Frazer, PA

chronic pain Phase IIIwww.tevapharm.com

hydromorphone intrathecal MallinckrodtHazelwood, MO

chronic pain Phase IIIwww.mallinckrodt.com

K-103-IP(COX inhibitor)

Kowa Research InstituteMorrisville, NC

arthritis pain Phase Iwww.kowaus.com

KRN5500(protein synthesis inhibitor)

DARA BiosciencesRaleigh, NC

peripheral neuropathy (Fast Track)

Phase IIwww.darabio.com

levorphanol extended release(abuse-deterrent drug delivery system)

Relmada TherapeuticsBlue Bell, PA

moderate to severe chronic pain Phase Iwww.relmada.com

Lyrica®

pregabalinPfizerNew York, NY

peripheral neuropathic pain (see also epilepsy)


mavatrep Janssen Research & DevelopmentRaritan, NJ

chronic pain Phase Iwww.janssenrnd.com

meloxicam nano-formulation Iroko PharmaceuticalsPhiladelphia, PA

osteoarthritis pain Phase IIIwww.iroko.com

NCE Eli LillyIndianapolis, IN

osteoarthritis pain Phase Iwww.lilly.com

neublastin Biogen IdecWeston, MANsGeneBallerup, Denmark

neuropathic pain Phase Iwww.biogenidec.com

NKTR-181(mu-opioid agonist)

Nektar TherapeuticsSan Francisco, CA

moderate to severe chronic pain(Fast Track)

Phase IIwww.nektar.com



Pain


NP-1998(capsaicin topical liquid)


neuropathic pain Phase IIwww.acorda.com

NXN-462(nNOS inhibitor)

NeurAxonMississauga, Canada

postherpetic neuralgia Phase IIwww.neuraxon.com

oxycodone/naloxone controlled release(OXN)

Purdue PharmaStamford, CT

severe chronic lower back pain Phase IIwww.purduepharma.com

PA65020(aspirin 650mg/omeprazole 20mgfixed-dose combination)

POZENChapel Hill, NC

chronic pain Phase Iwww.pozen.com

Pennsaid® 2%diclofenac transdermalsecond-generation

Nuvo ResearchMississauga, Canada

osteoarthritis pain application submittedwww.nuvoresearch.com

PF-05089771(Nav1.7 sodium channel inhibitor)

PfizerNew York, NY

chronic pain Phase Iwww.pfizer.com





PLX1100(ibuprofen/phosphatidylcholine)

PLx PharmaHouston, TX

osteoarthritis pain Phase IIwww.plxpharma.com

pregabalin controlled release PfizerNew York, NY

postherpetic neuralgia(see also epilepsy)


PTI-202(abuse-resistant opioid)

Pain TherapeuticsAustin, TX

moderate to severe chronic pain Phase I completedwww.paintrials.com

PTI-721(abuse-resistant opioid)

Pain TherapeuticsAustin, TX

moderate to severe chronic pain Phase I completedwww.paintrials.com

Qutenza®

capsaicin 8% patchAstellas PharmaTokyo, JapanNeurogesXSan Mateo, CA

HIV-associated neuropathy(Fast Track)

--------------------------------------diabetic neuropathy

application submittedwww.astellas.comwww.neurogesx.com-----------------------------------------Phase IIIwww.astellas.comwww.neurogesx.com



Pain


Remoxy™oxycodone controlled release (Mu-type opioid receptor agonist/abuse resistant)

Pain TherapeuticsAustin, TXPfizerNew York, NY

moderate to severe chronic pain application submittedwww.pfizer.com

rezatomidine(alpha adrenergic receptor agonist)

ACADIA PharmaceuticalsSan Diego, CAAllerganIrvine, CA

diabetic neuropathy Phase IIwww.acadia-pharm.comwww.allergan.com

S-117957 Purdue PharmaStamford, CTShionogiFlorham Park, NJ

neuropathic pain Phase Iwww.purduepharma.comwww.shionogi.com

SAR292833/GRC15300(TRVP3 antagonist)

Glenmark PharmaceuticalsMumbai, IndiaSanofi USBridgewater, NJ

neuropathic pain, osteoarthritis pain Phase IIwww.sanofi.com

SD-254(deuterium-substituted venlafaxine analogue)


neuropathic pain Phase Iwww.auspexpharma.com

SEP-228432(SRNDI inhibitor)


neuropathic pain Phase Iwww.sunovion.com

SKL-NP SK biopharmaceuticalsFair Lawn, NJ

neuropathic pain Phase IIwww.skbp.com

sufentanil(transdermal delivery system)

DURECTCupertino, CA

chronic pain Phase IIwww.durect.com

TAK-428(neurotrophic factor productionaccelerator)

Takeda Pharmaceuticals InternationalDeerfield, IL

diabetic neuropathy Phase IIwww.takeda.com

TEM(senrebotase)

AllerganIrvine, CA

postherpetic neuralgia Phase IIwww.allergan.com

V116517 Purdue PharmaStamford, CT

pain due to osteoarthritis of the knee, postherpetic neuralgia

Phase IIwww.purduepharma.com

V158866 (FAAH inhibitor)

VernalisWinnersh, United Kingdom

neuropathic pain Phase IIwww.vernalis.com



Pain


VBY-036(protease inhibitor)

VirobayMenlo Park, CA

neuropathic pain Phase Iwww.virobayinc.com

verapamil Calosyn PharmaSharon, MA

osteoarthritis pain Phase I/IIwww.calosynpharma.com

Vicodin® CRhydrocodone/paracetamolcontrolled release


back pain, osteoarthritis pain application submittedwww.abbvie.com

VM202(modified hepatocyte growth factor gene therapy)

ViroMedSeoul, South Korea

diabetic neuropathy Phase IIwww.viromed.co.kr

XEN402 Teva PharmaceuticalNorth Wales, PAXenon PharmaceuticalsBurnaby, Canada

postherpetic neuralgia Phase IIwww.tevapharm.comwww.xenon-pharma.com

YKP-509(carisbamate)

SK biopharmaceuticalsFair Lawn, NJ

neuropathic pain Phase IIwww.skbp.com

YKP-3089 SK biopharmaceuticalsFair Lawn, NJ

neuropathic pain(see also epilepsy)

Phase IIwww.skbp.com

Z160(N-type calcium channel antagonist)

ZalicusCambridge, MA

neuropathic pain, postherpetic neuralgia

Phase IIwww.zalicus.com

Z944 (T-type calcium channel antagonist)

ZalicusCambridge, MA

neuropathic pain Phase Iwww.zalicus.com

Zohydro ER™hydrocodone extended-release

ZogenixSan Diego, CA

moderate to severe chronic pain application submittedwww.zogenix.com

zucapsaicin(TRPV-1 agonist) (Orphan Drug)

Winston PharmaceuticalsVernon Hills, IL

chronic pain, postherpetic neuralgia(see also headache)

application submittedwww.winstonlabs.com





AFQ056(mavoglurant)


drug-induced dyskinesia in Parkinson’s disease

Phase IIwww.novartis.com

AQW051(alpha7 nicotinic acetylcholinereceptor agonist)


drug-induced dyskinesiain Parkinson’s disease

Phase II completedwww.novartis.com

autologous stem cell therapy NeuroGenerationLos Angeles, CA

Parkinson’s disease Phase Iwww.neurogeneration.com

AVE-8112(PDE4 inhibitor)

Sanofi USBridgewater, NJThe Michael J. Fox Foundationfor Parkinson’s ResearchNew York, NY

Parkinson’s disease Phase Iwww.sanofi.comwww.michaeljfox.org

AZD3241(myeloperoxidase inhibitor)

AstraZenecaWilmington, DE

Parkinson’s disease Phase IIwww.astrazeneca.com

CERE-120(AAV-NTN)

CeregeneSan Diego, CA

Parkinson’s disease Phase IIwww.ceregene.com

CVT-301(levodopa inhalation)

Civitas TherapeuticsChelsea, MA

Parkinson’s disease Phase IIwww.civitastherapeutics.com

davunetide intranasal Allon TherapeuticsVancouver, Canada

Parkinson’s disease(see also Alzheimer’s, other)

Phase Iwww.allontherapeutics.com

dipraglurant(ADX48621) (immediate release)

Addex TherapeuticsGeneva, Switzerland

levodopa-induced dyskinesia in Parkinson’s disease

Phase IIwww.addextherapeutics.com

DM-1992(carbidopa/levodopa controlled-release)

Depomed, Inc.Newark, CA

Parkinson’s disease Phase IIwww.depomed.com

Duopa®

levodopa/carbidopaintestinal gel (LCIG)(Orphan Drug)


advanced Parkinson’s disease (Fast Track)

application submittedwww.abbvie.com

fipamezole (alpha-2 adrenergic receptor antagonist)

Santhera PharmaceuticalsLiestal, Switzerland

Parkinson’s disease (Fast Track)

Phase II completedwww.santhera.com







Parkinson’s disease (see also Alzheimer’s, amyotrophic lateral sclerosis, multiple sclerosis, spinal cord injury, stroke)


GZ404477(AAV-hAADC gene therapy)

GenzymeCambridge, MA

Parkinson’s disease Phase Iwww.genzyme.com

HT-1067(MOA-B reversible inhibitor)

Dart NeuroScienceSan Diego, CA

Parkinson’s disease Phase Iwww.dartneuroscience.com

KW-6002(istradefylline)

Kyowa Hakko Kirin AmericaPrinceton, NJ

Parkinson’s disease application submittedwww.kyowa-kirin.com

levodopa/carbidopa extended release

IMPAX LaboratoriesHayward, CA

Parkinson’s disease application submittedwww.impaxlabs.com

NAV5001(123I-labelled imaging agent)


Parkinsonian disorder (diagnosis)(see also Alzheimer’s)

Phase IIIwww.navidea.com

Nurelin™ADS-5102/amantadine ER

Adamas PharmaceuticalsEmeryville, CA

levodopa-induced dyskinesiain Parkinson’s disease

Phase IIIwww.adamaspharma.com

NuroPro®

neurotrophic factor companion diagnostic

Amarantus BioSciencesSunnyvale, CA

Parkinson’s disease (diagnosis) Phase IIwww.amarantus.com

opicapone(COMT inhibitor)

BialLisbon, Portugal

Parkinson’s disease Phase Iwww.bial.com

OS-320(levodopa/carbidopa)

Osmotica PharmaceuticalWilmington, NC

Parkinson’s disease Phase IIIwww.osmoticausa.com

Posiphen®

R-phenserineQR PharmaBerwyn, PA

Parkinson’s disease(see also Alzheimer's)

Phase IIwww.qrpharma.com

PYM-50028 PhytopharmHuntingdon, United Kingdom

early stage Parkinson’s disease Phase IIwww.phytopharm.com

safinamide Newron PharmaceuticalsBresso, ItalyZambonBresso, Italy

Parkinson’s disease Phase IIIwww.newron.comwww.zambonpharma.com

tozadenant(adenosine A2A receptor antagonist)

Biotie TherapiesSouth San Francisco, CA UCBBrussels, Belgium

Parkinson’s disease Phase II/IIIwww.biotie.comwww.ucb.com





XP21279(dopamine receptor agonist)

XenoportSanta Clara, CA

Parkinson’s disease Phase IIwww.xenoport.com

Spasticity


CK-2127107 CytokineticsSouth San Francisco, CA

muscular atrophy associated with neuromuscular dysfunction, muscular weakness, and/or muscle fatigue

Phase Iwww.cytokinetics.com

CTP-354(GABA-A receptor modulator)

Concert PharmaceuticalsLexington, MA

muscle spasticity(see also pain)

Phase Iwww.concertpharma.com

Dysport®

abobotulinumtoxinAIpsen BiopharmaceuticalsBasking Ridge, NJ

focal spasticity of upper and lower limb in adults, adolescents and children

Phase IIIwww.ipsen.com

OS-440(arbaclofen extended release)

Osmotica PharmaceuticalMarietta, GA

muscle spasticity due to multiple sclerosis

Phase IIIwww.osmotica.com

SUN 09(baclofen extended release)

Sun Pharma Advanced ResearchMumbai, India

muscle spasticity due to multiple sclerosis

Phase IIIwww.sunpharma.in

Xeomin®

incobotulinumtoxinAMerz PharmaceuticalsGreensboro, NC

post-stroke spasticity Phase IIIwww.merzusa.com

Spinal Cord Injury


AC105(nervous system modulator)


spinal cord injury(Fast Track)

Phase IIwww.acorda.com

ATI355(anti-NOGO-A mAb) (Orphan Drug)


spinal cord injury Phase Iwww.novartis.com



Spinal Cord Injury


autologous stem cell therapy DaVinci BiosciencesCosta Mesa, CA

spinal cord injury in clinical trialswww.dvbiosciences.com

BA-210(Rho GTP-binding protein-inhibitor)(Orphan Drug)

BioAxone BioSciencesFt. Lauderdale, FL

spinal cord injury Phase IIwww.bioaxonebio.com



spinal cord injury (see also Alzheimer’s, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s, stroke)


HuCNS-SC®

adult neural stem cell therapyStemCellsNewark, CA

chronic spinal cord injury(see also genetic)

Phase I/IIwww.stemcellsinc.com

NEU2000 GNT PharmaYongin, South Korea

spinal cord injury(see also stroke)

Phase I completedwww.gntpharma.com

stem cell therapy TCA Cellular TherapyCovington, LA

spinal cord injury(see also amyotrophic lateral sclerosis)

Phase Iwww.tcacellulartherapy.com

SUN13837 (FGF-receptor agonist)

Daiichi SankyoParsippany, NJ

spinal cord injury Phase IIwww.dsi.com

Stroke


3K3A-APC(recombinant humanactivated protein C)

ZZ BiotechHouston, TX

stroke Phase Iwww.zzbiotech.com

ALD-401(bone marrow-derived adult stem cell therapy)

CytomedixGaithersburg, MD

stroke Phase IIwww.cytomedix.com

allogeneic mesenchymal bone marrow cell therapy

Stemedica Cell TechnologiesSan Diego, CA

ischemic stroke Phase I/IIwww.stemedica.com

Ampyra®

fampridine sustained-releaseAcorda TherapeuticsArdsley, NY

post-stroke deficits (see also other)




Stroke


betrixaban Portola PharmaceuticalsSouth San Francisco, CA

prevention of stroke in patients with atrial fibrillation

Phase IIwww.portola.com

CNTO-0007(cell therapy)

Janssen Research & DevelopmentRaritan, NJ

stroke Phase I/IIwww.janssenrnd.com

desmoteplase LundbeckDeerfield, IL

stroke (Fast Track)

Phase IIIwww.lundbeck.com



stroke (see also Alzheimer’s, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s, spinal cord injury)


GSK249320(myelin-associated glycoproteinmAb)


stroke Phase IIwww.gsk.com

methamphetamine intravenous Sinapis PharmaJacksonville, FL

stroke(see also brain injury)

Phase I completedwww.sinapispharma.com

MP-124(PARP inhibitor)

Mitsubishi Tanabe Pharma AmericaJersey City, NJ

acute ischemic stroke Phase Iwww.mt-pharma.co.jp

MultiStem®

stem cell therapyAthersysCleveland, OH

stroke Phase IIwww.athersys.com

NA-1(signal transduction pathway inhibitor)

NoNOToronto, Canada

acute ischemic stroke Phase II completedwww.nonoinc.ca

NEU2000 GNT PharmaYongin, South Korea

stroke(see also spinal cord injury)

Phase I completedwww.gntpharma.com


stroke recovery Phase IIwww.pfizer.com

RP-1127(glibenclamide)

Remedy PharmaceuticalsNew York, NY

stroke (see also brain injury)

Phase IIwww.remedypharmaceuticals.com

SAR126119(TAFIa inhibitor)


acute ischemic stroke Phase Iwww.sanofi.com

SB623(stem cell therapy)

SanBioMountain View, CA

stroke Phase I/IIwww.san-bio.com



Stroke


TS01(recombinant complementC1-inactivator-protein)

Thrombolytic Science InternationalCambridge, MA

stroke Phase Iwww.tsillc.com

Other


18F-AV-133imaging agent

Avid RadiopharmaceuticalsPhiladelphia, PA

neurodegenerative disorders (diagnosis)

Phase I/IIwww.avidrp.com

Abilify®

aripiprazole (once-weekly)

Otsuka America PharmaceuticalRockville, MD

Tourette’s syndrome Phase IIIwww.otsuka.com

ABT-354(serotonin-6 receptor antagonist)


neurological disorders Phase Iwww.abbvie.com

ABT-384 AbbVieNorth Chicago, IL

neurological disorders(see also Alzheimer’s)

Phase I completedwww.abbvie.com

Ampyra®

fampridine sustained releaseAcorda TherapeuticsArdsley, NY

cerebral palsy(see also stroke)


AP-1101 Ariel PharmaceuticalsBroomfield, CO

neuroprotection against postoperative cognitive decline and memory loss in patients undergoing extracorporeal cardiopulmonary bypass

Phase II

Botox®


juvenile cerebral palsy(see also headache, pain)

Phase IIIwww.allergan.com

BYM338(type II-B activin receptor modulator mAb)


inclusion body myositis Phase IIwww.novartis.com

CX1739(AMPA receptor agonist)

Cortex PharmaceuticalsGlen Rock, NJ

central sleep apnea Phase Iwww.cortexpharm.com

davunetide intranasal(Orphan Drug)

Allon TherapeuticsVancouver, Canada

progressive supranuclear palsy(Fast Track)(see also Alzheimer’s, Parkinson’s)

Phase II/IIIwww.allontherapeutics.com



Other


ecopipam(D1 dopamine receptor antagonist)

Psyadon PharmaceuticalsGermantown, MD

Tourette’s syndrome(see also genetic)

Phase I/IIwww.psyadonrx.com

EVP-0334(HDAC inhibitor)


neurodegenerative disorders Phase Iwww.envivopharma.com

Firdapse™amifampridine(Orphan Drug)


Lambert-Eaton myasthenic syndrome Phase IIIwww.catalystpharma.com

Gilenya®

fingolimodNovartis PharmaceuticalsEast Hanover, NJ

chronic inflammatorydemyelinatingpolyradiculoneuropathy

Phase IIIwww.novartis.com

glycerol phenylbutyrate(Orphan Drug)

Hyperion TherapeuticsSouth San Francisco, CA

hepatic encephalopathy Phase II completedwww.hyperiontx.com

human immune globulin (subcutaneous)

CSL BehringKing of Prussia, PA

chronic inflammatory demyelinating polyradiculoneuropathy

Phase IIIwww.cslbehring.com

idebenone(Orphan Drug)

Columbia University New York, NY Santhera PharmaceuticalsLiestal, Switzerland

MELAS syndrome(see also multiple sclerosis)

Phase IIwww.santhera.com

interleukin-7 CytherisRockville, MD

progressive multifocal leukoencephalopathy

Phase IIwww.cytheris.com

IPX159 IMPAX PharmaceuticalsHayward, CA

restless legs syndrome Phase IIwww.impaxpharma.com

MK-8616 (sugammadex)


neuromuscular blockade application submittedwww.merck.com

NBI-98854(VMAT2 inhibitor)

Neurocrine BiosciencesSan Diego, CA

drug-induced dyskinesia(Fast Track)

Phase IIwww.neurocrine.com

NH001(apomorphine subcutaneous)(Orphan Drug)

NeuroHealing PharmaceuticalsWaban, MA

coma(Fast Track)

Phase IIwww.neurohealing.com



Other


NNZ-2566(cytokine inhibitors/neuropeptide receptor modulator)

Neuren PharmaceuticalsBethesda, MD

Rett syndrome(Fast Track)(see also brain injury)

Phase Iwww.neurenpharma.com

OCR-002(ornithine phenylacetate) (Orphan Drug)

Ocera TherapeuticsSan Diego, CA

hepatic encephalopathy in patientswith acute liver failure (iv)(Fast Track)--------------------------------------hepatic encephalopathy in patients with liver cirrhosis (oral)(Fast Track)

Phase IIwww.ocerainc.com

-----------------------------------------Phase Iwww.ocerainc.com

placulumab Cephalon (Teva)Frazer, PA

sciatica Phase I/IIwww.tevapharm.com

pomaglumetad(LY2140023 monohydrate)


CNS disorders Phase Iwww.lilly.com

SD-809(VMAT inhibitor)


drug-induced dyskinesias, Tourette’s syndrome(see also Huntington’s)

Phase Iwww.auspexpharma.com

Soliris®

eculizumab (Orphan Drug)

Alexion PharmaceuticalsCheshire, CT

myasthenia gravis, severe and relaps-ing neuromyelitis optica

Phase IIwww.alxn.com

SPI-017 Sucampo PharmaceuticalsBethesda, MD

lumbar spinal stenosis Phase IIwww.sucampo.com

SPI-3608 Sucampo PharmaceuticalsBethesda, MD

spinal stenosis Phase Iwww.sucampo.com

Tardoxyl™pyridoxal phosphate

Medicure PharmaSomerset, NJ

drug-induced dyskinesia(Fast Track)

Phase IIwww.medicure.com

uridine triacetate (PN401)

Wellstat TherapeuticsGaithersburg, MD

neurodegenerative disorders Phase Iwww.wellstattherapeutics.com

vigabatrin(GABA-AT inhibitor)


Tourette’s syndrome Phase I/IIwww.catalystpharma.com


Glossary

Alzheimer’s disease—The most com-mon form of dementia, characterized by progressive and chronic deterioration of cognitive functions, including memory, thinking and reasoning. Early manifes-tations include forgetfulness, impaired ability to focus, and changes in mood and personality. As the disease progresses, there is a loss of computational ability, in addition to word-finding problems and dif-ficulty with ordinary activities. Ultimately, the disease leads to severe memory loss, complete disorientation, social withdrawal, loss of independence, and is fatal.

amyotrophic lateral sclerosis (Als)—Also known as Lou Gehrig’s disease, the most common of the motor neuron dis-eases, a group of rare disorders in which the nerves that control muscular activity degenerate within the brain and spinal cord causing weakness and wasting of the muscles.

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

attention deficit/hyperactivity disorder (ADHD)—ADHD is a complex neurologi-cal impairment that results in an over-active behavior pattern and a difficulty concentrating. While it primarily affects children, a growing number of adults are being diagnosed with the disorder. Boys are affected about three times as often as girls. Children with ADHD are fidgety, impulsive, reckless, irritable, emotionally immature and sometimes aggressive. Because their attention span is short, they do not conform to orderly routine. ADHD often leads to anti-social acts and difficulty learning, although IQ is normal. No definite cause has been established, but some researchers now believe genet-ics plays a role.

cerebral palsy—A general term for disor-ders of movement and posture resulting from damage to the brain in pregnancy, during birth, in the newborn period or in early childhood.

dementia—Degeneration of central nervous functions, such as memory and

learning capacity. The natural decline of these functions with age is grossly exag-gerated in dementia.

Duchenne muscular dystrophy—An inherited disorder that involves rapidly worsening muscle weakness. Other muscular dystrophies get worse much more slowly. Duchenne’s is caused by a defective gene. Because of the way the disease is inherited, males are more likely to develop symptoms than are women.

epilepsy—Recurrent seizures—transient neurological abnormalities caused by abnormal electrical activity in the brain—or temporary alteration in one or more brain functions. Seizures are a symptom of brain dysfunction and can result from a wide variety of diseases or injury.

Fast Track—A process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The status is assigned by the U.S. Food and Drug Administration. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. Gener-ally, determining factors include whether the drug will have an impact on such factors as survival, day-to-day function-ing, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially superior to existing therapy. Once a drug receives Fast Track designa-tion, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.

Friedreich’s ataxia—An inherited disease that causes progressive dam-age to the nervous system resulting in symptoms ranging from gait disturbance and speech problems to heart disease. “Ataxia,” which refers to coordination

problems such as clumsy or awkward movements and unsteadiness, occurs in many different diseases and conditions.

glioblastoma multiforme—The most common and most malignant of the as-trocytomas. The tumor grows so fast that it increases pressure in the brain, produc-ing headaches, slowed thinking, and if severe enough, sleepiness and coma.

glioma—A type of brain tumor arising from the supporting glial cells within the brain. Gliomas make up about 60 percent of all primary brain tumors.

Huntington’s disease—Huntington’s chorea is an uncommon, inherited dis-ease in which degeneration of the basal ganglia (structures deep in the brain) results in chorea (rapid, jerky, involuntary movements) and dementia (progressive mental impairment).

lennox-Gastaut syndrome—Character-ized by seizures and mental retardation in infants and young children.

metastases/metastatic—Areas of sec-ondary cancer that have spread from the primary or original cancer site.

migraine—Severe headache result-ing from an abnormal dilation of blood vessels deep within the brain. It can last from two hours to several days and is often accompanied by nausea, vomiting and sensitivity to noise and/or light.

multiple sclerosis (Ms)—Progressive disease of the central nervous system in which scattered patches of the covering of nerve fibers (myelin) in the brain and spinal cord are destroyed. Symptoms range from numbness and tingling to paralysis and incontinence.

muscular dystrophy—Inherited muscu-lar disorder of unknown cause in which muscle fibers slowly degenerate. Duch-enne MD is the most common type.

myasthenia gravis—A chronic autoim-mune neuromuscular disease character-ized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. The hallmark of myasthenia gravis


Glossary

is muscle weakness that increases during periods of activity and improves after periods of rest.

neuroblastoma—A tumor of the adrenal glands or sympathetic nervous system (the part of the nervous system respon-sible for certain automatic body func-tions, such as the control of heart rate). Neuroblastomas are the most common extracranial (outside the skull) solid tumors of childhood.

neuropathic pain—Caused by disease, inflammation, or damage to the periph-eral nerves, which connect the central nervous system (brain and spinal cord) to the sense organs, muscles, glands, and internal organs.

neuropathy—Disease, inflammation, or damage to the peripheral nerves, which connect the central nervous system to the sense organs, muscles, glands, and internal organs.

Orphan Drug—A drug to treat a disease that has a patient population of 200,000 or less, or a disease that has a patient population of more than 200,000 and a developmental cost that will not be re-covered from sales in the United States.

Parkinson’s disease—Chronic neurologic disease of unknown cause, characterized by tremors, rigidity and an abnormal gait.

Phase 0—First-in-human trials conduct-ed in accordance with FDA’s 2006 guid-ance on exploratory Investigational New Drug (IND) studies designed to speed up development of promising drugs by es-tablishing very early whether the tested compound behaves in human subjects as was anticipated from preclinical studies.

Phase I—Safety testing and pharmaco-logical profiling in humans.

Phase II—Effectiveness testing in humans.

Phase III—Extensive clinical trials in humans.

postherpetic neuralgia—A burning pain that may recur at the site of an attack of shingles months or even years after the illness.

prodrug—An inactive medicine that becomes active inside the body through metabolic processes. Prodrugs can be used to improve how a specific medi-cine is absorbed, distributed, metabo-lized or excreted.

restless legs syndrome—Restless legs syndrome is an overwhelming urge to move the legs usually caused by uncomfortable or unpleasant sensations in the legs.

spinal cord injury—Damage to the spinal cord which can cause loss of sensation, muscle weakness or paralysis.

stroke—Usually caused by atheroscle-rosis. It results in death or serious brain damage, such as paralysis or loss of speech. An ischemic stroke is caused by blocked or narrowed arteries that prevent sufficient blood and oxygen from reaching the brain.

Tourette syndrome (TS)—A neurologi-cal disorder characterized by repetitive, involuntary movements and vocalizations called tics. The early symptoms of TS are typically noticed first in childhood, with the average onset between the ages of 3 and 9. TS occurs in people from all ethnic groups; males are affected about three to four times more often than females. It is estimated that 200,000 Americans have the most severe form of TS, and as many as 1 in 100 exhibit milder and less complex symptoms such as chronic motor or vocal tics. Although TS can be a chronic condition with symptoms lasting a lifetime, most people with the condition experience their worst tic symptoms in their early teens, with improvement occurring in the late teens and continuing into adulthood.

The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” data-base based on the latest information. Report current as of July 18, 2013. The medicines in this report include medicines being developed by U.S. based companies conducting trials in the United States and abroad, PhRMA-member companies conducting trials in the United States and abroad, and foreign companies conducting clinical trials in the United States. The information in this report may not be comprehensive. For more 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 © 2013 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

the drug discovery, development and approval process

The U.S. system of new drug approvals is perhaps the most rigorous in the world.

It takes 10-15 years, on average, for an experi-mental drug to travel from lab to U.S. patients, according to the Tufts Center for the Study of Drug Development. Only five in 5,000 com-pounds that enter preclinical testing make it to human testing. And only one of those five is approved for sale.

On average, it costs a company $1.2 billion, including the cost of failures, to get one new medicine from the laboratory to U.S. patients, according to a recent study by the Tufts Center for the Study of Drug Development.

Once a new compound has been identified in the laboratory, medicines are usually developed as follows:

Preclinical Testing. A pharmaceutical company conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the compound is evalu-ated for safety.

Investigational New Drug Application (IND). After completing preclinical testing, a com-pany files an IND with the U.S. Food and Drug Administration (FDA) to begin to test the drug

in people. The IND shows results of previous experiments; how, where and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in the animal studies; and how the compound is manufac-tured. All clinical trials must be reviewed and ap-proved by the Institutional Review Board (IRB) where the trials will be conducted. Progress reports on clinical trials must be submitted at least annually to FDA and the IRB.

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

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

Clinical Trials, Phase III—The drug is given to a larger, more diverse patient population, often involving between 1,000 and 3,000 patients (but sometime many more thousands), to gener-

ate statistically significant evidence to confirm its safety and effectiveness. They are the lon-gest studies, and usually take place in multiple sites around the world.

New Drug Application (NDA)/Biologic License Application (BLA). Following the completion of all three phases of clinical trials, a company analyzes all of the data and files an NDA or BLA with FDA if the data successfully demonstrate both safety and effectiveness. The applications contain all of the scientific information that the company has gathered. Applications typically run 100,000 pages or more.

Approval. Once FDA approves an NDA or BLA, the new medicine becomes available for physi-cians to prescribe. A company must continue to submit periodic reports to FDA, including any cases of adverse reactions and appropriate quality-control records. For some medicines, FDA requires additional trials (Phase IV) to evaluate long-term effects.

Discovering and developing safe and effective new medicines is a long, difficult, and expensive process. PhRMA member companies invested an estimated $48.5 billion in research and develop-ment in 2012.

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

PRE-

DIS

COV

ERY

DRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG

3 – 6 Y E A RS 6 – 7 Y E A RS 0. 5 – 2 Y E A RS

100 – 300 1,000 – 3,00020 –80

PHASE 2

PHASE 3

PHASE 1

IND

SU

BM

ITTE

D

ND

A S

UB

MIT

TED

PHA

SE 4

: PO

ST-M

AR

KET

ING

SU

RVEI

LLA

NCE

NUMBER OF VOLUNTEERS

ONE FDA-APPROVED

DRUG

5,000 – 10,000

COMPOUNDS

250 5

Drug Discovery and Development: A LONG, RISKY ROAD

Medicines in Development Neurological Disorders 2013

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