First treatment for rare genetic condition

Morquio A syndrome (also known as mucopolysaccharidosis type IVA (MPS IVA)) is commonly diagnosed in early childhood and is life-long with no cure. People with Morquio A syndrome rarely live beyond the second or third decade of life, with respiratory and heart failure being the leading causes of mortality. As healthy children grow up, their endurance, as measured by the 6-minute walk test, improves and they can walk further each year.  However, the distance children with Morquio A syndrome can walk in six minutes falls every year as their endurance decreases.  By the time they are teenagers they have 75% less endurance than teenagers unaffected by Morquio A syndrome.(1,2) This lack of endurance leads to increased wheelchair use, loss of independence, high caregiver burden and poor quality of life.

By replacing the missing enzyme activity, Vimizim® significantly improves the endurance of patients with Morquio A syndrome as demonstrated by improved performance on the 6-minute walk test. In clinical trials, compared with placebo, patients treated with a once-weekly infusion of 2mg/kg of Vimizim® for just 24 weeks significantly increased the distance they could walk in six minutes.  The significant improvement seen in the walk test translates to an improved ability to perform endurance-based daily tasks, such as walking, bathing independently and getting dressed.

“This is fantastic news for all affected patients as they now have the choice of a disease modifying therapy to add to other measures to improve their quality of life. The impact for patients will be significant as they are now able to slow the progression of this devastating disorder,” said Dr Chris Hendriksz at Salford Royal NHS Foundation Trust, UK.

Morquio A syndrome, or mucopolysaccharidosis type IVA (MPS IVA), a rare lysosomal storage disorder, is a degenerative, potentially life-threatening, genetic condition that affects major organ systems in the body. It is caused by an inherited deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, a critical lysosomal enzyme responsible for the breakdown of cell waste products called glycosaminoglycans (GAGs). GALNS enzyme deficiency results in accumulation of the GAG substrates keratan sulphate (KS) and chondroitin-6-sulphate (C6S) in lysosomes (the cell waste disposal system) throughout the body. Accumulation of these GAG substrates leads to widespread, progressive cellular, tissue, and organ dysfunction, resulting in life-threatening complications.

Each individual with Morquio A syndrome is affected differently, with varied rates of disease progression and organ involvement. The syndrome can result in musculoskeletal complications leading to short stature as well as potentially severe heart, lung, nervous system, eyes, ears, nose and throat, liver, and dental problems. Life expectancy in Morquio A syndrome patients is limited and they rarely live beyond the second or third decade of life.

Morquio A syndrome impairs mobility and around 30-45% of people with the condition will use a wheelchair,(2,4)  reducing their quality of life and independence compared with more mobile patients.(5)  Parents of wheelchair bound patients spend more time and need to support patients completely for most aspects of life.(5) Reduced endurance and mobility can also hamper patients’ involvement in everyday activities,(6) such as at walking, bathing independently and getting dressed.

As Morquio A syndrome patients retain normal intelligence,(7) adult patients are able to work. However, a recent international patient-reported outcomes survey showed that around half of adults with Morquio A syndrome were unemployed.v The employed patients were more likely to be active and mobile; only 67% of employed patients used a wheelchair compared with all of the unemployed patients.(5) In addition, the level of unemployment among caregivers of people with Morquio A syndrome is high.(8)

There are an estimated 3000 people living with Morquio A syndrome in the developed world.

Vimizim® (elosulfase alfa) is an enzyme replacement therapy designed to target the underlying cause of Morquio A syndrome. It replaces the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme that is missing in people with Morquio A syndrome; a lack of this enzyme is responsible for the development of the condition. In a clinical trial of 176 Morquio A patients, those administered once-weekly Vimizim® 2mg/kg demonstrated a 22.5-metre (p=0.0174) improvement in the 6-minute walk test in only 24 weeks compared with patients taking a placebo. In the trial Vimizim was generally well tolerated.(3)

BioMarin, the makers of Vimizim®, develops and commercialises innovative biopharmaceuticals for serious genetic diseases and medical conditions. As part of the company’s commitment to patients and families with MPS, BioMarin has developed several enzyme replacement therapies for the treatment of MPS diseases. In fact, BioMarin has developed more treatments for MPS than any other biotech or pharmaceutical company. For additional information, please visit www.BMRN.com.