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Published on: December 20, 2017
Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease
Priya Sunil Kishnani1, Marc Nicolino, Thomas Voit
1Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. kishn001@mc.duke.edu
Insights
Recombinant human acid alpha-glucosidase (rhGAA) treatment improved survival, cardiac function, and motor skills in infants with Pompe disease. This therapy demonstrated safety and efficacy, offering better outcomes than expected without treatment.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Medicine
Background:
- Infantile-onset Pompe disease is a rare genetic disorder.
- It leads to progressive muscle weakness and organ damage.
- Enzyme replacement therapy is a potential treatment option.
Purpose of the Study:
- To evaluate the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in infantile-onset Pompe disease.
- To assess clinical outcomes including survival, cardiac function, growth, and motor development.
Main Methods:
- An open-label, multinational, multicenter study involving 8 infants with Pompe disease.
- rhGAA administered intravenously weekly for up to 153 weeks.
- Safety and efficacy monitored through adverse events, antibody titers, survival, ventilator use, echocardiograms, growth, and motor/cognitive function.
Main Results:
- After 52 weeks, 6 of 8 patients survived, and 5 were free from ventilators.
- Significant improvements observed in cardiomyopathy, growth, and cognitive function.
- Five patients achieved new motor milestones, with 3 walking independently; no drug-related deaths occurred.
Conclusions:
- rhGAA significantly improved ventilator-free survival in infantile-onset Pompe disease.
- The treatment demonstrated positive effects on cardiomyopathy, growth, and motor function.
- rhGAA is a safe and effective therapeutic option for this condition.
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.
