Rare Diseases Backgrounder: Selected Examples of Orphan Drugs in Development

Selected Examples of Orphan Drugs in Development For Rare Diseases Backgrounder

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. Nerve and muscle cells are particularly energy-demanding and are, therefore, more prone to cell damage or death due to mitochondrial dysfunction. One medicine in development may be able to prevent cell damage and increase the production of energy within impaired nerve and muscle tissue by preserving mitochondrial function and protecting cells from stress.

Lennox-Gastaut syndrome (LGS) – A severe form of childhood-onset 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 increases anti-seizure activity by enhancing the inhibition activity of the gamma-aminobutyric acid (GABA) neurotransmitter in the brain, of which patients with LGS have very low levels.

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 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 these proteins.

Stomach Cancer – 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 vessels and soft tissue), affecting about 4,500-6,000 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 inhibit tumor growth. It has also shown to prevent the proliferation of tumor cells lines while promoting cell death by directly targeting several oncogenic tyrosine kinase receptors.

Leukemia – Chronic lymphocytic leukemia (CLL) affects about 14,990 people each year in the United States, accounting for about one-third of all leukemia cases. CLL results from a mutation to the DNA of a lymphocyte, a type of white blood cell. This results in the replication and increase of abnormal lymphocytes in the blood which are unable to fight infection. The condition is not present at birth and scientists do not yet understand what causes the change in the DNA. A medicine in development targets the Bcl-2 protein, which appears to contribute to the resistance of cancer cells to chemotherapy. By reducing the amount of this protein in cancer cells, the medicine may enhance the effectiveness of chemotherapy.

Cushing’s Disease – Cushing’s disease is a rare but serious hormonal disorder caused by a pituitary gland tumor that triggers the production of excess cortisol. It is relatively rare – affecting an estimated 10 to 15 of every million people each year – and most commonly affects adults aged 20 to 50. It affects women five times more frequently than men. Complications of the disease can include osteoporosis, insulin resistance, high blood pressure, lipid disorders, kidney stones, mental illnesses and cardiovascular complications. A potential medicine in development aims to control excess cortisol secretion and its debilitating complications. The medicine targets multiple subtypes of a receptor for the hormone that controls the pituitary gland. The same medicine is also in development for acromegaly, a related hormonal disorder that develops when the pituitary gland produces too much growth hormone. There about 1,000 new cases of acromegaly diagnosed each year in the United States.

Orphan Drugs in Development for Rare Diseases, 2011

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