Duvoglustat HCl Increases Systemic and Tissue Exposure of Active Acid α-Glucosidase in Pompe Patients Co-administered with Alglucosidase α

Priya Kishnani, Mark Tarnopolsky, Mark Roberts, Kumarswamy Sivakumar, Majed Dasouki, Mazen M. Dimachkie, Erika Finanger, Ozlem Goker-Alpan, Karl A. Guter, Tahseen Mozaffar, Muhammad Ali Pervaiz, Pascal Laforet, Todd Levine, Matthews Adera, Richard Lazauskas, Sheela Sitaraman, Richie Khanna, Elfrida Benjamin, Jessie Feng, John J. FlanaganJay Barth, Carrolee Barlow, David J. Lockhart, Kenneth J. Valenzano, Pol Boudes, Franklin K. Johnson, Barry Byrne

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Duvoglustat HCl (AT2220, 1-deoxynojirimycin) is an investigational pharmacological chaperone for the treatment of acid α-glucosidase (GAA) deficiency, which leads to the lysosomal storage disorder Pompe disease, which is characterized by progressive accumulation of lysosomal glycogen primarily in heart and skeletal muscles. The current standard of care is enzyme replacement therapy with recombinant human GAA (alglucosidase alfa [AA], Genzyme). Based on preclinical data, oral co-administration of duvoglustat HCl with AA increases exposure of active levels in plasma and skeletal muscles, leading to greater substrate reduction in muscle. This phase 2a study consisted of an open-label, fixed-treatment sequence that evaluated the effect of single oral doses of 50 mg, 100 mg, 250 mg, or 600 mg duvoglustat HCl on the pharmacokinetics and tissue levels of intravenously infused AA (20 mg/kg) in Pompe patients. AA alone resulted in increases in total GAA activity and protein in plasma compared to baseline. Following co-administration with duvoglustat HCl, total GAA activity and protein in plasma were further increased 1.2- to 2.8-fold compared to AA alone in all 25 Pompe patients; importantly, muscle GAA activity was increased for all co-administration treatments from day 3 biopsy specimens. No duvoglustat-related adverse events or drug-related tolerability issues were identified.

Original languageEnglish (US)
Pages (from-to)1199-1208
Number of pages10
JournalMolecular Therapy
Issue number5
StatePublished - May 3 2017


  • Pompe disease
  • enzyme replacement therapy
  • pharmacokinetics
  • pharmacological chaperone

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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