2013 MEDICINES IN DEVELOPMENT REPORT Neurological Disorders A Report on Disorders of the Brain, Spinal Cord and Nerves PRESENTED BY AMERICA’s biopharmACEUTICAL RESEARCH COMPANIES Biopharmaceutical Companies Researching and Developing Nearly 450 Medicines for Neurological Disorders Neurological disorders—such as epi- Other medicines in development target lepsy, multiple sclerosis and Parkinson’s amyotrophic lateral sclerosis (ALS), disease—inflict great pain and suffering brain injuries, Huntington’s disease, on patients and their families, and every spinal cord injury, cerebral palsy, and Medicines in Development year costs the U.S. economy billions stroke. Among the many promising new For Neurological Disorders of dollars. Biopharmaceutical research medicines in development are: companies are developing 444 new • medicines to prevent and treat neu- A medicine that prompts the immune Application system to protect neurons affected by Submitted rological disorders. The medicines in development are either in human clinical ALS. Phase III trials or under review at the Food and • Gene therapy for the treatment of Phase II Drug Administration. They include: Alzheimer’s disease. Phase I • 82 medicines for Alzheimer’s disease, • Gene therapy to reverse the effects of which afflicts more than 5 million Parkinson’s disease. Americans. The new medicines being developed by 82 82 • 82 medicines for pain—100 million biopharmaceutical research companies U.S. adults experience chronic pain. reflect a growing understanding of the underlying mechanisms of neurological • 62 medicines for brain tumors—nearly disorders, which fuels scientific progress 62 70,000 Americans are diagnosed and pharmaceutical research. These medi- each year with a primary brain tumor. cines offer patients hope that more effec- • 38 medicines for multiple sclerosis, tive treatments may soon be available. 38 which afflicts an estimated 500,000 Americans. 28 27 Contents • 28 medicines for epilepsy and sei- Key Issues ......................................2 zures, which impact more than Disease Facts ..................................7 3 million Americans. Medicines in Development ...............11 Glossary ...................................... 49 • 27 medicines for Parkinson’s disease, Drug Development/ which affects as many as 1 million Approval Process ....................... 51 s Pain Americans. Epilepsy Alzheimer’ Parkinson’s • 25 medicines for headache, includ- Brain Tumors ing migraine, a condition that affects Multiple Sclerosis more than 37 million people. Innovative Medicines in the Pipeline orders such as Duchenne muscular dystrophy (DMD). In DMD, DNA deletions cause mutations in important Of the 444 medicines in development in the United States genes that encode for dystrophin, a structural pro- listed in this report (see page 11), many present innovative tein found in normal muscle. The loss of this protein new ways to target diseases. Some of them include: causes muscle fibers to disintegrate faster than they can be regenerated. One medicine in development • Gene Therapy to Restore Neuronal Function in targets restoration of dystrophin function and, as dys- Alzheimer’s—A gene therapy for the treatment trophin expression increases, there have been demon- of Alzheimer’s disease in clinical trials is designed strated improvements in patients’ ability to walk. to deliver nerve growth factor (NGF) to the brain. NGF is a naturally occurring protein important for • Gene Therapy as a Possible Approach for Parkinson’s neuron survival. The gene treatment is injected into Disease—Inserting genes into cells can alter the im- the brain region where neuron degeneration occurs pact the genes have on the proteins that are involved in Alzheimer’s disease. It is thought that the result- in a particular disease. These genes might alter or ing sustained expression of NGF in the neurons can replace a mutated gene or produce a new thera- restore their lost function, leading to memory and peutic protein entirely. In Parkinson’s disease, there cognition improvement. are a number of treatments addressing the disease’s symptoms, but none that replace the lost nerve cells • Targeted RNAi Therapy Approach for Duchenne resulting from Parkinson’s or that would stop disease Muscular Dystrophy—In clinical trials, RNAi therapies progression. More than one gene therapy in clinical have shown potential in treating neuromuscular dis- 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 82 Application Submitted Amyotrophic Lateral Sclerosis (ALS) 8 Phase III Attention-Deficit/Hyperactivity Disorder 19 Phase II Brain Injury 8 Phase I Brain Tumors 62 Epilepsy 28 Genetic Disorders 14 Headache 25 Huntington’s Disease 7 Multiple Sclerosis 38 Muscular Dystrophy 7 Pain 82 Parkinson’s Disease 27 Spasticity 6 Spinal Cord Injury 9 Stroke 19 Other 33 2 Medicines in Development Neurological Disorders 2013 to deliver neurturin to restore cells damaged in Parkinson’s patients and to protect them from fur- ther degeneration; these inactivated viruses pres- OFALZHEIMER’S ent a safe way to get these important therapeutic IMPORTANCE TREATMENT 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 5 control over body movement, ultimately resulting MILLION in paralysis and death. The one drug approved to AMERICANS treat ALS can modestly slow progression of the disease, but new treatments are needed. As our scientific understanding of the disease has grown, ARE LIVING WITH ALZHEIMER’S DISEASE 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 15 by ALS. MILLION AMERICANS BY 2050, THE NUMBER OF PATIENTS COULD TRIPLE ALzheimer’s: WITHOUT EFFECTIVE TREATMENT 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 2013 2050 growing. Existing medicines are able to treat the symptoms of the disease but cannot slow, $ $ prevent, or reverse the progressive dementia. 203 1.2 Disease-modifying treatments that could BILLION TRILLION delay the onset of the disease could reduce the cost of care of Alzheimer’s patients in 2050 by $447 billion. Researchers continue ALZHEIMER’S COSTS SOCIETY $203 BILLION to unravel the mysteries of the disease AND COULD INCREASE TO $1.2 TRILLION BYBY 20502050 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 5 50 are thought to contribute to the death of 447 YEARS FEWER BILLION nerve cells. One medicine in development DELAYED = VICTIMS + SAVED has shown promise in reducing both brain ONSET plaques and tangles. A gene therapy also in clinical trials is being explored to restore lost DELAYING DISEASE ONSET BY 5 YEARS COULD RESULT IN neuron function. 50% FEWER PATIENTS/SAVEPATIENTS/SAVE $447 BILLION BYBY 20502050 Medicines in Development Neurological Disorders 2013 3 Advancing Biomedical Science Breakthrough Research in Over the past decade, scientific advances and new technolo- Neurological Disorders gies have dramatically changed how medicines are discov- Early research discoveries often fuel the drug development ered. This new information is critical to the development of pathways that biopharmaceutical company researchers un- new treatments for neurological disorders. Greater knowl- dertake. These discoveries help researchers target a specific edge of how diseases work at the genetic and molecular level disease through certain mechanisms that may have been has allowed researchers to pursue new targets for therapy unknown before. Some noteworthy recent scientific discover- and better predict how certain biopharmaceuticals will affect ies in the field of neurology include: specific subpopulations of patients. • Researchers at Mount Sinai Medical Center found • Bioinformatics —Bioinformatics use systems and 10 genes that account for half of the genetic risk for mathematical models to advance the scientific un- Alzheimer’s. derstanding of living systems. At its simplest level, bioinformatics involves the creation and maintenance • Research at the National Institutes of Health found of biological databases, including DNA sequences. that a protein linked with some early-onset Parkin- son’s disease cases regulates how the body processes • Biomarkers —Every disease leaves a signature of dietary fats. The study suggests there could be a link molecular “biomarkers” in our body—genes that turn between the defective protein and early-onset Parkin- on and off or proteins released into the bloodstream. son’s disease. Biomarkers measured in blood and other samples can tell us the state of our health and how we might • Scientists at the University of Chicago have uncovered respond to treatment. a previously unknown process of protein production where a single gene can create two separate proteins • Molecular Targeting—The idea behind molecular from the same messenger RNA simultaneously. They targeting is to design drugs that specifically attack the believe this discovery will open the door for new molecular pathways