Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: A clinical study and review of the literature

Genet Med. 2020 May;22(5):898-907. doi: 10.1038/s41436-019-0738-0. Epub 2020 Jan 6.

PMID: 31904026

Aleena A. Khan, MBBS, Laura E. Case, PT, DPT, Mrudu Herbert, MD, MPH, Stephanie DeArmey, MHS, PA-C, Harrison Jones, PhD, Kelly Crisp, CCC-SLP, MA, Kanecia Zimmerman, MD, Mai K. ElMallah, MD, Sarah P. Young, PhD, Priya S. Kishnani, MD

Summary: This study reports the effects of higher recombinant human acid-α glucosidase (rhGAA) dosing regimen on clinical outcomes, efficacy, and safety profile in patients with IPD and early-onset LOPD. It is shown that in early-onset Pompe disease, higher rhGAA doses are safe, and improve gross motor outcomes, lingual ability, pulmonary function tests, and biochemical markers.

Abstract

Purpose: The standard dose of 20 mg/kg every other week of enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) is inadequate to stop the long-term progression of myopathy in Pompe disease. This study reports the effects of higher rhGAA dosing regimen on clinical outcomes, efficacy, and safety profile in patients with IPD and early-onset LOPD, who showed clinical plateau or decline with a standard dose of ERT.

Methods: Patients with infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) with onset before the age of 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation were studied retrospectively. The researchers were able to achieve long-term follow-up of up to 18 years. As the dosage was increased, physical therapy, lingual ability, biochemical, and pulmonary assessments were made.

Results: Higher doses of up to 40 mg/kg weekly were given to 11 patients with IPD (n = 7) or LOPD (n = 4). Gross motor function improved in 9/10 patients, lingual power improved in 6/6 patients, and pulmonary function improved in 4/11 patients. At 40 mg/kg weekly, there were significant reductions in urinary glucose tetrasaccharide, creatine kinase, aspartate aminotransferase, and alanine aminotransferase relative to lower doses (p < 0.05). No safety or immunogenicity concerns were observed at higher doses.

Conclusion: In early-onset Pompe disease, higher rhGAA doses are safe, and improve gross motor outcomes, lingual ability, pulmonary function tests, and biochemical markers. Dose escalation should be considered in patients with clinical and functional decline.

Keywords: alglucosidase alfa, Pompe disease, enzyme replacement therapy, high dose, recombinant human GAA