Rare Diseases

February 27, 2007

More than 300 Medicines Now in Development to Treat Rare Diseases

There are more than 300 medicines currently in development to treat or prevent hundreds of rare diseases, according to a new report released today by the Pharmaceutical Research and Manufacturers of America (PhRMA). Genetic Alliance and the National Organization for Rare Disorders (NORD) joined PhRMA in releasing the report. (Click here to see the full report.)

The National Institutes of Health estimates that there are approximately 6,000 rare diseases affecting 25 million Americans. A rare disease is defined as a condition affecting fewer than 200,000 people in the United States. In the past, treatment options for such conditions have been non-existent or limited, but approval of several new medicines in this research sector over the last few years has fostered great progress. Since 1995, more than 160 medicines were approved to treat rare diseases, compared to 108 in the decade before and fewer than 10 in the 1970s.

“Advances in science, such as a better understanding of molecular and genetic causes of disease, have given researchers important new insights to better treat rare diseases, which are often more complex than other diseases,” said Billy Tauzin, PhRMA president and CEO. “PhRMA member companies are committed to the search for treatments for these diseases and are making strides everyday.”

The report details progress by America’s pharmaceutical research companies with 303 medicines currently in human clinical trials or awaiting approval by the U.S. Food and Drug Administration (FDA).

Examples of medicines in development for rare diseases include:

A monoclonal antibody for chronic sarcoidosis, an immune system disorder.
A medicine for Lennox-Gastaut syndrome, a severe form of epilepsy.
Gene therapy for cystic fibrosis.
A medication for epidermolysis bullosa, a group of inherited disorders where skin blisters develop in response to minor trauma.
A medicine for Friedreich's ataxia, a genetic disorder.

“The companies undertaking the difficult and costly effort of developing drugs for rare disorders are making a profound impact on the lives of individuals and families with rare disorders,” said Sharon F. Terry, MA, president and CEO of the Genetic Alliance. “They focus on the question ’what matters’ for people living every day with these diseases.”

The Orphan Drug Act of 1983 provided tax relief and some market exclusivity for companies that develop an orphan drug. That legislation is credited with the explosion in drug approvals for rare diseases after 1983. Under the Orphan Drug Act, 1,679 medicines have been designated orphan drugs (not all are approved) as of January 10, 2007.

“Thanks to the Orphan Drug Act and the combined efforts of the patient community, scientific researchers and industry, treatments have been brought to market for many rare diseases that previously had none,” said Diane Edquist Dorman, vice president for public policy at the National Organization for Rare Disorders. “NORD thanks the pharmaceutical industry for all it has accomplished over the past quarter century, and we look forward to working with PhRMA to address the challenges to be faced in the next 25 years.”

“Biopharmaceutical research is entering an exciting new era with our growing understanding of the genome and powerful scientific research tools,” added Tauzin. “This is a time of hope for patients with rare diseases. Experts predict the number of orphan drugs will rise in the coming years as more new medicines are developed that target specific genetic disorders.”

Research on rare diseases includes: rare cancers such as liver cancer and melanoma; neurologic disorders such as multiple sclerosis and muscular dystrophy; infectious diseases such as anthrax and West Nile virus; and others such as cystic fibrosis.

SELECTED EXAMPLES OF ORPHAN DRUGS IN DEVELOPMENT FOR RARE DISEASES

Cancer, Stomach – Gastrointestinal stromal tumor (GIST) is a rare cancer affecting the digestive tract or the abdomen. GIST is a sarcoma (a cancer of the connective tissue or supportive tissue, such as bone, cartilage, fat, muscle, blood vessles and soft tissue), affecting about 4,000 people each year in the United States. It is believed to be caused by random, genetic mutations in the cell surface proteins called tyrosine kinase receptors. One medicine in development targets and inhibits multiple kinases involved in the formation of blood vessels (angiogenesis) and appears to reduce tumor growth.

CIAS1-associated periodic syndromes (CAPS) – A genetic auto inflammatory disorder that encompasses several rare diseases associated with mutations in the CIAS1 gene. Inflammatory symptoms of CAPS are due to mutations in the gene called “cryopyrin” (CIAS1). These mutations result in the body’s overproduction of interleukin-1 (IL-1), a protein that stimulates the inflammatory process. In excess, this protein can be harmful and has been linked to a variety of inflammatory diseases. One medicine in development is designed to attach to and neutralize the protein in the blood stream before it can attach to cell-surface receptors and generate signals that can trigger disease. Once the protein is attached to the medicine it cannot bind to cell surface receptors and is flushed from the body.

Epidermolysis bullosa (EB) – A group of inherited skin diseases where painful blisters and open sores develop in response to minor trauma. In severe cases, it can involve the eyes, tongue, and esophagus, and can produce scarring and disabling musculoskeletal deformities. One of every 50,000 live births is affected by some type of EB. A synthetic version of a molecule originally isolated from the thymus gland is a regulating molecule found in mammalian cells and plays an important role in the regeneration, remodeling, and healing of injured or damaged tissues.

Friedreich’s ataxia – A genetic, neurodegenerative disorder that can affect many systems in the body. Onset of symptoms is usually between the ages of five and 15. About 50,000 people in the United States have the disease. It is characterized by muscle weakness and loss of coordination (ataxia) in the arms and legs; vision impairment, hearing loss, and slurred speech; aggressive scoliosis (curvature of the spine); diabetes or carbohydrate intolerance; and an enlarged heart (cardiomyopathy). These symptoms reflect the death of cells in certain parts of the nervous system as a result of cell (mitochondrial) dysfunction. One small molecule in development may be able to prevent cell damage and increase the production of energy within impaired nerve a muscle tissue through preserving mitochondrial function and protecting cells from stress.

Lennox-Gastaut syndrome – A severe form of epilepsy that is characterized by frequent episodes of seizures and, in many cases, abnormal delays in coordination of mental and muscular activity. Seizures usually begin before four years of age. Seizure types, which vary among patients, include tonic (stiffening of the body, upward deviation of the eyes, dilation of the pupils, and altered respiratory patterns), atonic (brief loss of muscle tone and consciousness, causing abrupt falls), atypical absence (staring spells), and myoclonic (sudden muscle jerks). There may be periods of frequent seizures mixed with brief, relatively seizure-free periods. Lennox-Gastaut syndrome can be caused by brain malformations, perinatal asphyxia, severe head injury, central nervous system infection and inherited degenerative or metabolic conditions. In 30-35 percent of cases, no cause can be found. An estimated 1,400 to 4,500 new cases of the syndrome are diagnosed each year in the U.S. One medicine in development is focused on treating the seizures associated with the disease and has shown to reduce seizure frequency.

Leukemia – Chronic lymphocytic leukemia (CLL) affects about 10,020 people each year in the United States. CLL results from an injury to the DNA of a single cell, a lymphocyte, in the bone marrow. The condition is not present at birth and scientists do not yet understand what causes the change in the DNA. A monoclonal antibody in development works by binding a protein to certain tumor cells to enhance the destruction of the tumors and prevent its growth and survival. This process stimulates the body’s immune system to attack and kill the tumor cells. The medicine is also being tested in multiple myeloma, a cancer of the plasma cells. Plasma cells, part of the immune system, are one type of white blood cells. About 16,570 new cases of myeloma are diagnosed each year in the United States.

Sarcoidosis – A multi-system, autoimmune disorder characterized by the abnormal formation of inflammatory masses or modules (granulomas). Virtually any organ can be affected; however, granulomas most often appear in the lungs or the lymph nodes. Symptoms can occasionally appear suddenly but usually appear gradually. When viewing x-rays of the lungs, sarcoidosis can have the appearance of tuberculosis or lymphoma. One medicine in development targets specific proteins in the body’s immune system to help control the development of inflammation. The medicine attaches to and blocks the action of the protein.