BioMarin is paying $22 million up front to acquire ZyStor Therapeutics, a Wisconsin-based biotech firm developing enzyme replacement therapies (ERTs) for lysosomal storage disorders (LSDs). ZyStor shareholders could receive another $93 million contingent on the achievement of certain development, regulatory and commercial milestones.
The acquired firm's lead candidate ZC-701 is expected to start in clinical trials during early 2011 as a potential treatment for Pompe disease. The product comprises a fusion of insulin-like growth factor 2 and alpha glucosidase. ZyStor claims preclinical studies suggest ZC-701 has a 10-fold higher affinity for the mannose-6-phosphate (M6P) receptor than Genzyme’s alglucosidase alfa product Myozyme®, and will be able to deliver much higher levels of enzyme to the lysosomes of muscle cells.
BioMarin notes that ZyStor’s Pompe disease product could also be developed faster than its own Pompe disease candidate, BMN-103, and result in lower development costs, much lower cost of goods and reduced capital investment. “The acquisition of ZyStor gives us the opportunity to introduce a superior product for fulfil an unmet medical need and is a perfect fit in our core business,” states Jean-Jacque Bienaime, BioMarin CEO. “It not only provides us with a promising product candidate for Pompe disease but also an exciting new platform technology.”.
ZyStor says estimates suggest the worldwide market for ERTs against LSDs reached some $2.8 billion in 2008, and the total market for Pompe disease is currenty estimated to be worth more than $1 billion. The firm is developing a pipeline of ERTs based on its Glycosylation Indpendent Lysosomal Targeting (GILT) technology. GILT is designed to directly deliver the functional enzyme needed to correct the metabolic process in the lysosomes of LSD patients . The technology embeds a target directing GILT peptide tag within the therapeutic enzyme, as a means to promote the enzyme’s internalization into diseased cells. This is accomplished through binding of the GILT tag to the M6P receptor found on the surface of the target cell, ZyStor explains.
This approach is expected to result in a number of benefits compared with traditional approaches to ERT. These include less expensive manufacturing of the ERT because M6P does not need to be incorporated into the product in order to achieve therapeutic uptake by the cells. ZyStor says data also suggest GILT may be able deliver enzymes across the blood-brain barrier, opening up new potential avenues for treating LSD patients with neurological pathologies.
BioMarin currently has three FDA-approved products on the market. Kuvan® is an oral small molecule therapeutic for the treatment of phenylketonuria (PKU) that was developed in partnership with Merck Serono. Naglazyme® is BioMarin’s internally developed and commercialized product for the treatment of mucopolysaccharidosis VI (MPS VI). Aldurazyme® for the treatment of mucopolysaccharidosis I (MPS I), was developed through a 50/50 joint venture with Genzyme. The firm achieved net product revenues of $315.7 million in 2009, up 25.4% on 2008.
BioMarin’s clinical pipeline includes the Phase II-stage PEG-PAL for the treatment of phenylketonuria, and 6R-BH4, for the treatment of peripheral arterial disease. An N-acetylegalactosamine-6 sulfatase (GALNS) ERT is in Phase I development for Morquio A syndrome. BMN-195 is a small molecule inducer of utrophin gene expression, which is also undergoing Phase I testing as a potential therapy for Duchenne muscular dystrophy.
Genzyme reported Myozyme sales of $92.1 million in the second quarter of 2010, up 16 per cent compared with the same period in 2009. Myozyme sales for calendar year 2009 were $325 million, and are projected to reach $470-500 in 2010. In May FDA approved Genzyme’s Lumizyme® specifically for the treatment of patients aged eight years and over with late-onset (non-infantile) Pompe disease.