MeDiCiNes iN DevelopMeNt 2013 Neurological Disorders

2013 REPORT

Medicines in Development

Neurological Disorders

A Report on Disorders of the Brain, Spinal Cord and Nerves

presented by america's biopharmaceutical research companies

Multiple

Epilepsy Sclerosis

Medicines in Development For Neurological Disorders

Application Submitted Phase III Phase II

Phase I

82

82

62

38

28

27

ParkinsPoani'sn

Biopharmaceutical Companies Researching and Developing Nearly 450 Medicines for Neurological Disorders

Neurological disorders--such as epilepsy, 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 neurological 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 seizures, which impact more than 3 million Americans.

?27 medicines for Parkinson's disease, which affects as many as 1 million Americans.

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 medicines offer patients hope that more effective treatments may soon be available.

Contents

Key Issues.......................................2 Disease Facts...................................7 Medicines in Development................11 Glossary....................................... 49 Drug Development/

Approval Process........................ 51

?25 medicines for headache, including migraine, a condition that affects more than 37 million people.

BraAilznhTeiummeorr'ss

Innovative Medicines in the Pipeline

Of 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 resulting 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 protein 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 dystrophin expression increases, there have been demonstrated improvements in patients' ability to walk.

?Gene Therapy as a Possible Approach for Parkinson's Disease--Inserting genes into cells can alter the impact 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 therapeutic 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

Medicines in Development for Neurological Disorders By Disease and Phase

Some medicines are listed in more than one category

Alzheimer's Disease Amyotrophic Lateral Sclerosis (ALS) Attention-Deficit/Hyperactivity Disorder

Brain Injury Brain Tumors

Epilepsy Genetic Disorders

Headache Huntington's Disease

Multiple Sclerosis Muscular Dystrophy

Pain Parkinson's Disease

Spasticity Spinal Cord Injury

Stroke Other

8 19

8

14 7 7

28 25

38

27 6

9 19 33

82 62

82

Application Submitted Phase III

Phase II

Phase I

2

Medicines in Development Neurological Disorders 2013

to deliver neurturin to restore cells damaged in Parkinson's patients and to protect them from further degeneration; these inactivated viruses present 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 neurodegenerative 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 create 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.

Medicines in Development Neurological Disorders 2013

IMPORTANCEOF

ALZHEIMER'S

TREATMENT

5

MILLION

AMERICANS

ARE LIVING WITH ALZHEIMER'S DISEASE

15

MILLION

AMERICANS

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

2013

$203 BILLION

2050

$1.2

TRILLION

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

5 50% 447 YEARS

= + DELAYED

ONSET

FEWER

VICTIMS

$

BILLION SAVED

DELAYING DISEASE ONSET BY 5 YEARS COULD RESULT IN

50% FEWER PATIENTS/SAVE $447 BILLION BY 2050

3

Advancing Biomedical Science

Over the past decade, scientific advances and new technologies have dramatically changed how medicines are discovered. This new information is critical to the development of new treatments for neurological disorders. Greater knowledge 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 understanding of living systems. At its simplest level, bioinformatics involves the creation and maintenance of biological databases, including DNA sequences.

? B iomarkers--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.

? M olecular Targeting--The idea behind molecular targeting is to design drugs that specifically attack the molecular pathways that cause disease without disrupting the normal functions in our cells and tissues.

? N anotechnology--You can't see it, but soon it will be everywhere. Nanotechnology is the science of building microscopic devices at the molecular and atomic levels. In medicine, nanotechnology may also be used to help diagnose and treat diseases.

? P ersonalized 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 Disorders

Early research discoveries often fuel the drug development pathways that biopharmaceutical company researchers undertake. These discoveries help researchers target a specific disease through certain mechanisms that may have been unknown before. Some noteworthy recent scientific discoveries 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 Parkinson'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 Parkinson'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 mutation 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.

4

Medicines in Development Neurological Disorders 2013

? 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 inhibitor 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 Biotechnology 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 effective in treating brain disorders such as Huntington's, Alzheimer's, and Parkinson's.

Public/Private Partnerships Critical to Advancing Science

Collaboration 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 leading 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 agencies, non-profit organizations, and biopharmaceutical industry members. The goal of the Initiative is to track Alzheimer's disease progression, establish quality standards, and validate biomarkers to be used in clinical

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.

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 candidates. 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 biopharmaceutical research companies, academic institutions, regulatory agencies, patient advocacy groups, research foundations, scientific associations and consultants that work collaboratively through a precompetitive partnership to accelerate development of therapeutics for neurodegenerative diseases.

Medicines in Development Neurological Disorders 2013

5

New Neurological Medicines Approved for Patients

The new medicines being developed today build on the medical progress seen over the last decade or so. Below are examples 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 therapeutically inactive until metabolized in the body. It is intended to provide a safer, abuse-resistant and effective alternative to amphetamine-based therapies for ADHD.

Alzheimer's Disease

? Namenda? (memantine) is the first treatment approved 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)

? TecfideraTM (dimethyl fumarate; BG-12) is a first-line oral treatment for relapsing forms of MS. It is believed 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 inflammation 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 channel blocker approved for the adjunctive treatment of partial-onset seizures in adults. While the exact mechanism 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.

6

Medicines in Development Neurological Disorders 2013

Selected Facts about Neurological Disorders

Alzheimer's Disease and Other Dementias1

?An estimated 5.4 million Americans have Alzheimer's disease (AD). Today, someone in America develops AD every 68 seconds. 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.

Amyotrophic Lateral Sclerosis2

?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.

Brain Injury3

?According to the U.S. Centers for Disease Control (CDC) Injury Prevention Center, the leading causes of traumatic brain injury (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.

Brain Tumors4

?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 nervous 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.

Medicines in Development Neurological Disorders 2013

7

Selected Facts about Neurological Disorders

Epilepsy5

?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.

Genetic Disorders6

?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.

Headache

?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 sufferers 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 productivity. The annual U.S. direct medical costs attributable to migraine were estimated at $1 billion in 1999.7

Huntington's Disease9

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

8

Medicines in Development Neurological Disorders 2013

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download