BMN701 Phase 3 in rhGAA Exposed Subjects with Late Onset Pompe Disease

  • Research type

    Research Study

  • Full title

    A Phase 3 Switchover Study of the Efficacy and Safety of BMN701 (GILT-tagged Recombinant Human GAA) in rhGAA Exposed Subjects with Late-Onset Pompe Disease

  • IRAS ID

    135259

  • Contact name

    Derralyn Hughes

  • Contact email

    rmgvdah@ucl.ac.uk

  • Sponsor organisation

    Biomarin Pharmaceutical, Inc.

  • Eudract number

    2013-001768-48

  • Clinicaltrials.gov Identifier

    NCT01924845

  • Research summary

    This is a Phase 3 open label study investigating a new molecule, BMN701, for the treatment of Late-onset Pompe disease in patients current receiving rhGAA (commercially available GAA). Pompe disease is a progressive, life limiting disease with patients experiencing progressive muscle weakness caused by the accumulation of glycogen in skeletal and cardiac muscle. Glycogen accumulation results from alpha-glucosidase (GAA) deficiency, an enzyme important in glycogen metabolism. Life expectancy is reported to relate to the age of onset of disease, and residual GAA activity, with premature death resulting from respiratory failure.

    The study molecule, BMN 701, utilises a Glycosylation Independent Lysosomal Targeting ’GILT’ tag to deliver recombinant human alpha glucosidase (rhGAA) to lysosomes of skeletal and cardiac muscle via interaction with the IGF-2 cell surface receptor. Licensed rhGAA therapy currently uses other modes of lysosomal delivery. Concentrations of delivered GAA achieved in licensed drugs are low and efficacy is limited. It is anticipated that BMN701 with its GILT tag may be more efficacious at delivering rhGAA to lysosomes. The potential benefits of treatment in a progressive and ultimately fatal condition, in which current medications have limitations, are attractive.

    The objective of this single arm, open-label, switch-over study is to test the ability of BMN 701 (GILT tagged rhGAA) to improve respiratory function and endurance in patients with Pompe disease currently treated with rhGAA. Ambulatory patients who have mild to moderate respiratory impairment will switch directly to receive BMN 701 20 mg/kg by IV infusion every other week. The change in value in the primary endpoint, Maximum Inspiratory Pressure (MIP) and secondary endpoints, Maximum Expiratory Pressure (MEP) and 6 minute walk distance (6MWD), will be measured as the difference between the Baseline value and the Week 24 value within each individual subject.

  • REC name

    West Midlands - Coventry & Warwickshire Research Ethics Committee

  • REC reference

    13/WM/0373

  • Date of REC Opinion

    1 Nov 2013

  • REC opinion

    Further Information Favourable Opinion