The lowdown: In April 2006, Genzyme received FDA approval for the recombinant enzyme Myozyme (alglucosidase alpha) — the first therapy approved for Pompe disease — manufactured at a limited capacity of 160 L at their Framingham plant. While Myozyme was being developed, in 2004 Genzyme spent US$53 million to expand the manufacturing capacity at its Allston Landing plant to produce the enzyme in 2,000 L batches. Now, the FDA has informed Genzyme that Myozyme produced at the larger scale will need a separate regulatory application because of differences in the carbohydrate structures compared with the original approved product. This is a cause for concern because Myozyme, which provides an exogenous source of alglucosidase alpha (deficiency of which causes Pompe disease), uses its carbohydrate groups to bind to receptors and enter its target cells to become activated through intracellular proteolytic cleavage.
To achieve FDA approval for Myozyme produced at the 2,000 L scale, the agency has recommended that Genzyme initiates a rolling BLA review process by submitting results from their Late Onset Treatment Study (LOTS) that achieved its coprimary efficacy endpoints in December 2007. The 90 patients enrolled in LOTS received Myozyme produced using the scaled-up process that has reportedly been approved in ∼40 countries worldwide.
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