Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease - PubMed (original) (raw)

Clinical Trial

doi: 10.1016/j.jpeds.2006.02.035.

Marc Nicolino, Thomas Voit, R Curtis Rogers, Anne Chun-Hui Tsai, John Waterson, Gail E Herman, Andreas Amalfitano, Beth L Thurberg, Susan Richards, Mark Davison, Deyanira Corzo, Y T Chen

Affiliations

Clinical Trial

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease

Priya Sunil Kishnani et al. J Pediatr. 2006 Jul.

Abstract

Objective: To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.

Study design: We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use, echocardiograms, growth, and motor and cognitive function.

Result: After 52 weeks of treatment, 6 of 8 patients were alive, and 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated; no death was drug-related.

Conclusion: rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.

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Conflict of interest statement

Conflict of Interest: P.S.K., A.A., and Y.T.C. have received research/grant support from Genzyme Corporation. P.S.K. and M.N. are members of the Pompe Disease Advisory Board for Genzyme Corporation. Y.T.C. has served as a consultant for Genzyme Corporation. If therapy for Pompe disease proves successful commercially, Duke University and the inventors of the cell line used to generate the enzyme used in this clinical trial (CHO-1 in this manuscript) may benefit financially pursuant to the Duke University’s Policy on Inventions, Patents, and Technology Transfer.

Figures

Figure 1

Figure 1

Antibody titers against rhGAA with time. Log dilution titer is shown in the left y-axis; dilution titer is shown in the right y-axis.

Figure 2

Figure 2

LVMI results with time. LVMI was calculated from 2-dimensional echocardiography by a central cardiologist reader.

Figure 3

Figure 3

Mean weight and length z-scores with time.

References

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