Lysosomal Storage Disease Market

LSDs are composed of a group of about 50 rare genetic disorders caused by the patients’ lack of specific lysosomal enzymes. In all, Nature Reviews estimates the worldwide prevalence of LSDs ranges from approximately 1,000 to 10,000 individuals depending on the specific type of LSD, as summarized below.1  LSDs are chronic diseases that, if untreated, lead to painful debilitation and death.  Their symptoms are severe and affect multiple tissues and organs of the body. The combination of the severity of the diseases, the high cost of caring for untreated patients and the relatively high cost of manufacturing enzyme replacement therapies has historically enabled Genzyme to obtain attractive pricing for its marketed enzyme replacement therapies, including Cerezyme, Fabrazyme, Myozyme and Aldurazyme.

           Lysosomal Storage Disease Global Prevalence

Pompe Disease	5,000 - 10,000
Gaucher Disease	5,000 - 10,000
Fabry Disease	4,000 - 5,000
Hurler, Huler-Scheie Syndrome (MPS I)	3,000 - 4,000
Hunter Syndrome (MPS II)	2,000
Maroteaux-Lamy Syndrome (MPS VI)	1,100
Niemann Pick-B Syndrome	1,000
Moquio Syndrome (MPS IV)	1,000

            Approximate number of individuals affected

The lysosome, commonly referred to as the cell’s recycling center, is the organelle that contains digestive enzymes responsible for the metabolism of macromolecules, such as carbohydrates, proteins, and lipids, into substances that the cell can utilize. LSDs, which are inherited diseases, are triggered when a genetic deficiency or defect in one of these digestive enzymes leads to the accumulation of substrates within the cell, thereby disrupting normal cellular function. This toxic buildup of unwanted molecules leads to painful disabilities and disease, affecting different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. Each LSD results from mutations in different genes that translate into a deficiency in the corresponding enzyme activity and is generally classified as a function of the abnormal accumulating molecule. Individuals afflicted with LSDs can die at an early age or suffer from a painfully debilitating disease for several decades. Babies with LSDs generally appear normal at birth, but symptoms appear progressively over the first few months of life. Examples of symptoms include changes in facial appearance, bone deformities, joint stiffness, pain, loss of skills such as speech as well as respiratory and cardiac problems. The severity of the individual disease is variable and correlated to the amount of residual enzyme activity produced by the defective gene. In some cases, patients die in their teens or earlier, while others survive into adulthood. LSDs are progressive diseases and symptoms may not appear until later in life. There is currently no cure for LSDs, and symptomatic treatment is the only available option.

Genzyme is the most well known company that has developed and markets enzyme replacement therapies for LSDs. Genzyme’s enzyme replacement therapies treat Gaucher, Fabry, Pompe and Mucopolysaccharidosis I diseases and achieved aggregate  worldwide sales of over $2.1 billion in 2008. Genzyme’s products are priced at approximately $200,000 to $350,000 per year per patient and have gross margins of approximately 78%.2  Shire plc (“Shire”), BioMarin Pharmaceutical, Inc. (“BioMarin”) and Actelion Pharmaceuticals Ltd. (“Actelion”) also market therapies for certain LSDs, as summarized below.