Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial

Klinge, Lars; Straub, Volker; Neudorf, Ulrich; Schaper, J.; Bosbach, T.; Görlinger, Klaus; Wallot, M.; Richards, Susan; Voït, Thomas

doi:10.1016/j.nmd.2004.10.009

Cited by 168 publications

(113 citation statements)

References 14 publications

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“…Results from several different trials with CHO enzyme and also transgenic enzyme from rabbit milk in earlier trials have shown that patients treated early in the disease, prior to the development of extensive tissue damage, are likely to have the best outcome 101–105. A clinical trial of 18 patients with classic infantile Pompe disease treated with CHO cell derived rhGAA at age ≤ 6 months was recently completed 106.…”

Section: Genetic Counseling Prenatal Diagnosis and Screeningmentioning

confidence: 99%

Pompe disease diagnosis and management guideline

Kishnani

Steiner

Bali

et al. 2006

Genetics in Medicine

493

583

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Section: Genetic Counseling Prenatal Diagnosis and Screeningmentioning

confidence: 99%

Pompe disease diagnosis and management guideline

Kishnani

Steiner

Bali

et al. 2006

Genetics in Medicine

493

583

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“…Furthermore, there are only a few reports on brain imaging in infants with classic Pompe disease. This may be attributed to the early mortality usually observed in untreated patients, the lack of close monitoring OF CNS parameters due to the historical endpoints chosen to prove the efficacy of ERT (Amalfitano et al 2001;Kishnani et al 2006bKishnani et al , 2007Klinge et al 2005; Van den Hout et al 2001, or to difficulties of cognitive testing and the risk of sedation for MRI in patients on ERT who may still have significant respiratory muscle weakness and/or cardiomyopathy. Furthermore, it also became evident that not all patients responded equally well to ERT regarding motor development, and it has been shown that this is dependent on CRIM status and hypothesized to be directly mediated by antibody response to ERT (Kishnani et al 2010).…”

Section: Discussionmentioning

confidence: 99%

CRIM‐negative infantile Pompe disease: 42‐month treatment outcome

Rohrbach

Klein

Köhli-Wiesner

et al. 2010

J of Inher Metab Disea

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Pompe disease is a rare lysosomal glycogen storage disorder characterized by deficiency of acid !-glucosidase enzyme (GAA) and caused by mutations in the GAA gene. Infantile-type Pompe disease is a multiorgan disorder presenting with cardiomyopathy, hypotonia, and muscular weakness, which is usually fatal. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) has recently been shown to be effective and subsequently yielded promising results in cross-reactive immunologic material (CRIM)-positive patients. CRIM-negative patients showed a limited response to ERT and died or were ventilator dependant. Over a period of 44 months, we monitored cognitive and motor development, behavior, auditory function, and brain imaging of a CRIM-negative infantile Pompe disease patient on rhGAA and monoclonal anti-immunoglobulin E (anti-IgE) antibody (omalizumab) treatment due to severe allergic reaction. Cardiorespiratory and skeletal muscle response was significant, with almost normal motor development. Cognitive development-in particular, speech and language-deviated increasingly from normal age-appropriate development and was markedly delayed at 44 months, unexplained by moderate sensorineural hearing impairment. Brain magnetic resonance imaging (MRI) at 18, 30, and 44 months of age revealed symmetrical signal alteration of the deep white matter. Titer values of IgG antibodies to rhGAA always remained <1:800. The potential role of omalizumab in immune modulation remains to be

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“…Because infantile-onset Pompe disease is a rapidly fatal disorder and clinical trials have shown that treatment with rhGAA can improve survival, cardiac and respiratory function, growth, and motor development, [5][6][7][8][9] ethics forbade using a placebo group in this study. Instead an untreated historic reference cohort was culled from a group of cases with infantile-onset Pompe disease identified through a retrospective chart review by Kishnani et al 10 The source group included 168 patients from nine countries and 33 different sites; 55% of patients were born in 1995 or later.…”

Section: Historical Control Groupmentioning

confidence: 99%

Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease

Nicolino

Byrne

Wraith

et al. 2009

Genetics in Medicine

260

209

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Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid ␣-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort. Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P Ͻ 0.001) and the risk of invasive ventilation by 58% (P ϭ 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid ␣-glucosidase; no patients withdrew from the study because of safety concerns. Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence. Genet Med 2009:11(3):210-219.

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Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial

Cited by 168 publications

References 14 publications

Pompe disease diagnosis and management guideline

Pompe disease diagnosis and management guideline

CRIM‐negative infantile Pompe disease: 42‐month treatment outcome

Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease

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