title: Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.
abstract: Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy.
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Case
authors.affiliation: Genzyme, a sanofi company, Cambridge, Massachusetts, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Bjartmar
authors.affiliation: Genzyme, a sanofi company, Cambridge, Massachusetts, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Alberta Children's Hospital, Alberta, Canada.
authors.forename: Robin
authors.initials: R
authors.lastname: Casey
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, IL, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Clancy
authors.affiliation: University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Majed
authors.initials: M
authors.lastname: Dasouki
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: DeArmey
authors.affiliation: Infusion Associates, Grand Rapids, Michigan, USA.
authors.forename: Khan
authors.initials: K
authors.lastname: Nedd
authors.affiliation: Adirondack Pediatrics, Glens Falls, New York, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Nevins
authors.affiliation: The Royal Children's Hospital, Victoria, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Peters
authors.affiliation: Genzyme, a sanofi company, Cambridge, Massachusetts, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Phillips
authors.affiliation: Parker Hill Oncology & Hematology, PC, Roxbury Crossing, Massachusetts, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Spigelman
authors.affiliation: Children's National Medical Center, District of Columbia, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Tifft
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA. Electronic address: priya.kishnani@duke.edu.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056947:Enzyme Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects; D009465:Neuromuscular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011897:Random Allocation; D016896:Treatment Outcome; D055815:Young Adult; D000520:alpha-Glucosidases / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007074:Immunoglobulin G; D009465:Neuromuscular Agents; C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: Alglucosidase alfa; Clinical decline; Dose; Enzyme replacement therapy; Infantile onset; Late onset; Pompe disease