BioMarin Pharmaceutical Inc. announced that it has initiated a pivotal phase III trial for N-acetylgalactosamine 6-sulfatase (GALNS or BMN 110), intended for the treatment of the lysosomal storage disorder Mucopolysaccharidosis Type IVA (MPS IVA), also called Morquio A Syndrome.

“In under two years, we have progressed the GALNS programme from clinical trial Application to initiation of the phase III trial. We have received FDA feedback and have finalized the design of the phase III pivotal trial,” said Jean-Jacques Bienaime, chief executive officer of BioMarin. “The study will be conducted at approximately 40 centres worldwide including Brazil, Japan, Taiwan, most Western European countries, Canada and the US The trial is expected to enroll approximately 160 subjects and will be the largest enzyme replacement therapy trial conducted. There are no therapeutic options for MPS IVA patients who have a high unmet medical need. Initiation of this well-designed pivotal study is an important milestone for both the company and the MPS IVA community.”

The phase III trial is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of GALNS in patients with MPS IVA. The study will explore doses of two mg/kg/week and two mg/kg/every other week for a treatment period of 24 weeks. The primary endpoint is the six-minute walk test, and the secondary endpoints are the three-minute stair climb test and urine Keratan Sulfate concentration.

Mucopolysaccharidosis IVA (MPS IVA, also known as Morquio A Syndrome) is a disease characterized by deficient activity of N-acetylgalactosamine 6-sulfatase (GALNS) causing excessive lysosomal storage of Keratan Sulfate (KS). This excessive storage causes a systemic skeletal dysplasia, short stature, and joint abnormalities, which limit mobility and endurance. Malformation of the thorax impairs respiratory function, and odontoid hypoplasia and ligamentous laxity cause cervical spinal instability and potential cord compression. Other symptoms may include hearing loss, corneal clouding, and heart valvular disease. Initial symptoms often become evident in the first five years of life. Depending on severity of the disease, age of diagnosis will vary.

The rate of incidence of MPS IVA is as yet unconfirmed and varies among different populations but estimates vary between 1 in 200,000 live births and 1 in 250,000 live births. There are several studies that have documented the incidence as high as 1 in 76,000 live births in Northern Ireland. The estimated prevalence is between 1,000 and 1,500 patients in the US, EU and Japan and between 1,500 to 2,000 patients in the rest of the world for a total of 2,500 to 3,500 patients. Over 1,000 MPS IVA patients worldwide have been identified through The International Morquio Organization (IMO) survey and the BioMarin MorCAP registry programme.

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions and it comprises of four approved products and multiple clinical and pre-clinical product candidates. Approved products include Naglazyme (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan (sapropterin dihydrochloride) Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany; and Firdapse (amifampridine phosphate), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS).