Velaglucerase alfa Produces Clinical Benefits in Pediatric Subpopulation

Velaglucerase alfa is a novel enzyme replacement therapy being evaluated as a treatment for people with type 1 Gaucher disease. At the recent Lysosomal Disease Network World Symposium, Ari Zimran, a researcher with the Gaucher Clinic at Shaare Zedek Medical Center in Jerusalem, Israel, presented analyses of velaglucerase alfa therapy in pediatric patients enrolled in a phase III double-blind study (TKT032). TKT032 included 25 patients, of which 7 (28%) were aged 2 to 17 years. Eligible participants had Gaucher-related anemia and one or more of the following disease symptoms: thrombocytopenia, moderately enlarged spleen, or increased liver volume.

Investigators randomly assigned patients to receive a 1-hour infusion of 60 U/kg or 45 U/kg of velaglucerase alfa every other week for 1 year. For the subgroup analyses, results for the two treatment arms were combined. After 12 months of treatment, patients showed improvement from baseline across nearly all measures. Hemoglobin concentration increased a mean of 20% and platelet counts increased a mean of 54%. Normalized by body weight, mean spleen volume decreased 47% and mean liver volume normalized by body weight decreased 13%. Zimran said these outcomes were consistent with those seen in the overall study population. The sample size was too small, however, for the results to be considered statistically significant but Zimran described them as “remarkable.”

None of the children in the study experienced serious or severe adverse events related to treatment with velaglucerase alfa. The most common adverse events overall included headache, nasopharyngitis, pyrexia, nasal congestion, productive cough, vomiting, and injury. None of the pediatric patients developed antibodies to velaglucerase alfa. “We have shown an excellent safety profile,” Zimran said.

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Shire plc, the biopharmaceutical company that manufactures velaglucerase alfa using a proprietary gene activation technology, filed a New Drug Application with the FDA in 2009 and received fast-track designation. A decision is expected February 28, 2010. In an interview with last month, Zimran said velaglucerase alfa is likely to be similar to Cerezyme—the standard treatment for type 1 Gaucher disease—in safety and efficacy.