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FDA advisory committee recommends approval of 2,000-L alglucosidase alfa
Alglucosidase alfa is approved for treatment of Pompe disease, a rare genetic disorder that affects approximately 2,000 Americans.
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The FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 16 to 1 that alglucosidase alfa should be produced at the 2,000-L bioreactor scale for the treatment of late-onset Pompe disease.
Genzyme is seeking a U.S. Biologics License Application for alglucosidase alfa (Myozyme) at the 2,000-L scale. The FDA approved a 160-L scale in April 2006, which is currently sold in 43 countries. However, there is not enough manufacturing capacity to produce all of the drugs needed at the 160-L scale, according to Genzyme.
The FDA meeting focused on clinical data from the Late Onset Treatment Study (LOTS), a randomized, double-blind, placebo-controlled trial of 90 patients with Pompe disease. The analysis revealed no statistically significant difference in rate of change in the six-minute walk test between the 2,000-L product and placebo based on the amended, pre-specified statistical analysis of the primary efficacy endpoints. However, based on the original statistical analysis plan, the FDA reported a 28.1-meter estimated change from baseline in distance walked during a six-minute walk test between the 2,000-L product and placebo (P=.035). Based on both analysis plans, there was a 3.4% difference in percent predicted upright forced vital capacity in favor of the 2,000-L product (P=.006). Safety analysis revealed increased immunogenicity and risk for anaphylaxis with the 2,000-L product.
“This analysis of the safety and efficacy of replacement therapy in Pompe disease represents a difficult, complex decision. There is no other enzyme treatment modality for this often devastating disease and there are issues regarding supply,” said acting chair Kenneth D. Burman, MD, chief of the Endocrine Section, Department of Medicine at Washington Hospital Center.
John R. Teerlink, MD, associate professor of medicine at the University of California, San Francisco, voted against the 2,000-L product, stating, “I do not believe there was any statistically, very persuasive evidence of clinically meaningful efficacy here. I think we are being given a false choice between approving the 2,000-L scale agent or nothing, given that the 160-L scale product is currently available and theoretically,160-L production could be expanded.”
The committee voted unanimously that the 2,000-L product should not be restricted to the adult-onset population. Genzyme has proposed a 2,000-L scale indication limited to patients with symptom-onset after 2 years of age and without hypertrophic cardiomyopathy. Additionally, the committee voted that post-marketing studies should be required to continue assessing the updated effectiveness and safety of alglucosidase alfa.
Formal FDA action is expected by Nov. 29, 2008. – by Katie Kalvaitis