Alglucosidase alfa 1.65g/1litre infusion bags

Aim: Treatment options for late-onset Pompe disease (LOPD) include enzyme replacement therapy (ERT) with alglucosidase alfa (alg), cipaglucosidase alfa plus miglustat (cipa + mig) and avalglucosidase alfa. However, only one randomized controlled trial (RCT) directly compared cipa + mig and alg and had relatively few ERT-naive patients. A multilevel network meta-regression (ML-NMR) integrated individual patient data and aggregate data into indirect treatment comparisons, with relative effects adjusted to any target population, to compare the efficacy of cipa + mig and alg. Materials & methods: A Bayesian ML-NMR was conducted to compare the efficacy of cipa + mig and alg for 6-minute walk distance (6MWD, meters) and percent predicted forced vital capacity (ppFVC) across any target population, using patientlevel and aggregate data from RCTs (PROPEL, COMET, LOTS) and phase I/II and open-label extension (OLE) trials (PROPEL OLE, LOTS OLE, COMET OLE, ATB200-02, NEO-1/NEO-EXT), adjusting for baseline covariates. Relative effect estimates were obtained for 6MWD and ppFVC change from baseline to week 52. Two networks were analyzed: network A (RCTs only) and network B (RCTs and single-arm OLE and phase I/II studies matched to comparator arms). To assess the impact of prior ERT exposure, simulations were conducted by only varying ERT duration among included covariates. Results: For cipa + mig compared with alg, both networks were associated with relative increases in 6MWD (mean difference [95% credible interval], Bayesian probability for network A: 13.48 m [6.79, 19.85], >99.9%; network B: 12.59 m [7.89, 17.45], >99.9%) and ppFVC (network A: 1.63% [0.71, 2.60], >99.9%; network B: 3.17% [2.53, 3.81], >99.9%). Network B suggested cipa + mig was favorable (>99.9%) in all groups for both end points and appeared more favorable with increasing ERT duration. Conclusion: Cipa + mig was associated with an improvement in 6MWD and ppFVC relative to alg independent of prior ERT exposure, which appeared more favorable when all available evidence was used. These data could inform decision-making in treating ERT-naive and ERT-experienced patients with LOPD.

Abstract licence: CC BY

Abstract: Pompe disease, also referred to as glycogenosis type II, is a rare, autosomal recessive disorder that results from the deficiency of the glycogen-degrading enzyme acid α-glucosidase. The classical form presents shortly after birth with muscle hypotonia, cardiac, and respiratory failure resulting in a fatal outcome. The late onset of Pompe disease has a very variable onset and disease presentation that often causes a delayed diagnosis. Until now enzyme replacement therapy with alglucosidase alfa is the only causative therapy option for Pompe patients that can slow down disease progression. However, uncertainty remains about the efficacy regarding survival and quality of life in Pompe patients under this very cost-intensive treatment. This paper provides a systematic review of the literature stressing different aspects of enzyme replacement therapy in infantile and late onset Pompe patients. Keywords: lysosomal storage disease, glycogenosis type II, acid maltase deficiency, IOPD, LOPD, enzyme replacement therapy

Abstract licence: CC BY-NC 3.0

Glycogen storage disease type 2, Pompe disease, is a progressive muscle disorder with a wide range of phenotypic presentations, caused by an inherited deficiency of the enzyme acid alpha-glucosidase. Although only a few patients have been treated with recombinant human alpha-glucosidase from rabbit milk since 2004, enzyme replacement therapy (ERT) with alglucosidase alfa has been licensed for the treatment of Pompe disease since 2006. Here, a systematic review [1] evaluates the clinical efficacy and safety of alglucosidase alfa treatment in juvenile and adult patients with late-onset Pompe disease (LOPD). Studies of alglucosidase alfa treatment in patients with LOPD, published up to October 2012, were identified using an electronic search of the EMBASE and MEDLINE databases, and manual searches of the reference lists. Data on ERT outcomes were extracted from the selected papers and analyzed descriptively. No statistical analyses were performed owing to data heterogeneity. Twenty-two studies containing clinical data from 437 LOPD patients were analyzed. Overall, at least two-thirds of patients were stabilized or exhibited improvements in creatine kinase levels, and muscular and/or respiratory function following treatment with alglucosidase alfa. Enzyme replacement therapy was well tolerated; the majority of adverse events were mild or moderate infusion-related reactions. Alglucosidase alfa treatment offers an effective and well tolerated treatment that attenuates the progression of LOPD in the majority of patients. Although first insights are upcoming, further research is required to investigate reliable prognostic factors such as age at treatment start, phenotypic presentation, and genotypic characteristics, of which may enable better clinical and therapeutic management of LOPD patients.

Abstract licence: CC BY 2.0