Efficacy, safety profile, and immunogenicity of alglucosidase alfa produced at the 4,000-liter scale in US children and adolescents with Pompe disease: ADVANCE, a phase IV, open-label, prospective study

Hahn, Si Houn; Kronn, David; Leslie, Nancy; Peña, Loren; Tanpaiboon, Pranoot; Gambello, Michael J.; Gibson, James B.; Hillman, Richard E.; Stockton, David W.; Day, John W.; Wang, Raymond; Haack, Kristina An; Shafi, Raheel; Sparks, Susan; Zhao, Yang; Wilson, Catherine L; Kishnani, Priya S.

doi:10.1038/gim.2018.2

Cited by 26 publications

(53 citation statements)

References 27 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Numerous studies in children and adults have shown improvement of muscle strength, stabilization of pulmonary function, decreased fatigue, and extended survival. However, there is variation in response and not all patients respond equally well (Broomfield et al, 2016;de Vries et al, 2012;Gungor et al, 2016;Hahn et al, 2018;Kuperus et al, 2017;Papadopoulos et al, 2017;Regnery et al, 2012;Stepien, Whitby, Roberts, & Sharma, 2015;Strothotte et al, 2010;van Capelle et al, 2010;.…”

mentioning

confidence: 99%

Extension of the Pompe mutation database by linking disease‐associated variants to clinical severity

et al. 2019

View full text Add to dashboard Cite

Pompe disease is an autosomal recessive lysosomal storage disorder caused by disease‐associated variants in the acid alpha‐glucosidase (GAA) gene. The current Pompe mutation database provides a severity rating of GAA variants based on in silico predictions and expression studies. Here, we extended the database with clinical information of reported phenotypes. We added additional in silico predictions for effects on splicing and protein function and for cross reactive immunologic material (CRIM) status, minor allele frequencies, and molecular analyses. We analyzed 867 patients and 562 GAA variants. Based on their combination with a GAA null allele (i.e., complete deficiency of GAA enzyme activity), 49% of the 422 disease‐associated variants could be linked to classic infantile, childhood, or adult phenotypes. Predictions and immunoblot analyses identified 131 CRIM negative and 216 CRIM positive variants. While disease‐associated missense variants were found throughout the GAA protein, they were enriched up to seven‐fold in the catalytic site. Fifteen percent of disease‐associated missense variants were predicted to affect splicing. This should be confirmed using splicing assays. Inclusion of clinical severity rating in the Pompe mutation database provides an invaluable tool for diagnosis, prognosis of disease progression, treatment regimens, and the future development of personalized medicine for Pompe disease.

show abstract

mentioning

confidence: 99%

Extension of the Pompe mutation database by linking disease‐associated variants to clinical severity

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The CONSORT diagram was published previously. 8 The one excluded patient had previously received commercial 4000 L rhGAA. At consent, ages of IOPD patients were 1.0-15.5 years (mean ± SD, 4.4 ± 3.52 years; median, 3.4 years); those of LOPD patients were 1.1-18.7 years (mean ± SD, 6.0 ± 4.19 years; median, 6.1 years).…”

Section: Resultsmentioning

confidence: 99%

“…Further details are in ADVANCE efficacy publication supplementary materials. 8 All IOPD patients were analyzed together.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease

Kishnani

Gibson

Gambello

et al. 2019

Genetics in Medicine

Self Cite

View full text Add to dashboard Cite

on behalf of the Pompe ADVANCE Study Consortium Purpose: To characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date. Methods: Patients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments. Results: Of 113 enrollees (60 male/53 female) aged 1-18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T (n = 23), c.−32-13T>G (n = 13), and c.525delT (n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material-negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.−32−13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total %scores (mean ± SD, median, range): overall 46.3 ± 33.0% (47.9%, 0.0-100.0%), IOPD 41.6 ± 31.64% (38.9%, 0.0-99.7%), LOPD: 61.8 ± 33.2 (70.9%, 0.0-100.0%). Conclusion: ADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.

show abstract

“…Pompe disease (DP) or glycogenosis type II is a rare, progressive, autosomal recessive disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA, 3.2.1.20) [1] [2]. The multi-systemic lysosomal storage of glycogen and the release of other hydrolases into the cytoplasm cause cell death and autophagic pathway disorders, especially in the smooth, striated and cardiac muscles, nerve tissue and liver [3] [4] [5].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Technological Dependence Characteristics on a Series of Brazilian Cases with Infantile Onset Pompe Disease in Enzyme Replacement Therapy

Thomazinho¹,

Pelissari²,

Duarte³

et al. 2019

OJCD

View full text Add to dashboard Cite

Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement therapy (ERT), with recombinant human GAA for the early onset PD patient, a relevant field of clinical research due to the benefits regarding survival rate has been widely documented worldwide. Objective: To describe the clinical characteristics and the ERT effects in a series of Brazilian patients with infantile onset PD (IOPD) under ERT. Methods: Brazilian patients diagnosed with IOPD under ERT were recruited through their physicians participating in the International Pompe Disease Registry from 2009 to 2017. Data were collected by an online survey. Results: 10 IOPD patients were identified through the survey with a death rate of 30% and technology dependency rate reported as How to cite this paper:

show abstract

Efficacy, safety profile, and immunogenicity of alglucosidase alfa produced at the 4,000-liter scale in US children and adolescents with Pompe disease: ADVANCE, a phase IV, open-label, prospective study

Cited by 26 publications

References 27 publications

Extension of the Pompe mutation database by linking disease‐associated variants to clinical severity

Extension of the Pompe mutation database by linking disease‐associated variants to clinical severity

Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease

Clinical and Technological Dependence Characteristics on a Series of Brazilian Cases with Infantile Onset Pompe Disease in Enzyme Replacement Therapy

Contact Info

Product

Resources

About