Safety of switching to Migalastat from enzyme replacement therapy in Fabry disease: Experience from the Phase 3 ATTRACT study

Hughes, D.A.; Nicholls, Kathy; Sunder‐Plassmann, Gere; Jovanović, Ana; Feldt‐Rasmussen, Ulla; Schiffmann, Raphael; Giugliani, Roberto; Jain, Vipul; Viereck, Christopher; Castelli, Jeffrey P.; Skuban, Nina; Barth, Jay; Bichet, Daniel G.

doi:10.1002/ajmg.a.61105

Cited by 13 publications

(10 citation statements)

References 11 publications

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“…The authors showed that renal function was maintained during 18 months of migalastat or ERT; moreover, migalastat significantly reduced cardiac mass compared with ERT, and no difference was reported on the other evaluated endpoints (renal, cardiac or cerebrovascular events, plasma lyso-Gb3 concentration, and patient-reported outcomes) [ 12 ]. Finally, the switch of treatment was well tolerated, as highlighted by the same authors in the following paper [ 13 ].…”

Section: Discussionmentioning

confidence: 96%

“…Although there has not been yet a consensus on when to choose migalastat over ERT, some criteria have been developed, which include: age 16 years and older, a confirmed amenable mutation, an eGFR > 30 mL/min/1.73 m 2 , compliance with every-other-day oral administration, and no intention by female patients to become pregnant. Patients' preference and hypersensitivity to ERT are also factors in considering the best treatment option [13]. Theoretically, the chaperoning of α-Gal by migalastat to lysosomes may better mimic natural enzyme trafficking and result in more constant α-Gal activity than ERT [12].…”

Section: Introductionmentioning

confidence: 99%

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Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data

Riccio¹,

Zanfardino

Ferreri

et al. 2020

Eur J Hum Genet

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The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18–66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data

Riccio¹,

Zanfardino

Ferreri

et al. 2020

Eur J Hum Genet

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“…After the approval of enzyme replacement therapy (ERT), it become the most popular treatment option for Fabry disease. Orally administered pharmacological chaperone migalastat hydrochloride also provide a beneficial effect on GLA amenable mutations [30]. Recent study showed that >28% Japanese families had amenable mutations to migalastat [31].…”

Section: Discussionmentioning

confidence: 99%

“…Recent study showed that >28% Japanese families had amenable mutations to migalastat [31]. However, timing the initiation of therapy is most crucial to get maximum beneficial effects [30,32,33]. The international guidelines for ERT are also being set up for presymptomatic patients [34].…”

Section: Discussionmentioning

confidence: 99%

Future clinical and biochemical predictions of Fabry disease in females by methylation studies of the GLA gene

Hossain

Wu²,

Yanagisawa³

et al. 2019

Molecular Genetics and Metabolism Reports

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Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-gal A). The clinical variability of the phenotypes of Fabry disease in females is still poorly understood. The degree of aberrant methylation of non-mutated alleles is thought to have significant effects on X-chromosome inactivation (XCI). We previously reported that one heterozygous Fabry female showing classical phenotypes had complete methylation of the non-mutated allele of the GLA gene. In this report, we summarized 36 heterozygous females with a clinical severity score based on the FAbry STabilization indEX (FASTEX). We measured their α-gal A activity and plasma/ serum globotriaosylsphingosine (lyso-Gb3) accumulation and performed electron microscopy of skin biopsies. We analyzed the methylation-sensitive restriction enzyme sites throughout the GLA gene, including the 5’UTR, and found a single Sac II site and multiple Hha I and Hpa II sites aggregated in exon 1 and the 5’UTR. One Hpa II sequence in exon 7 was also detected as a methylation-sensitive site. With methylation-sensitive restriction enzymes, methylated and non-methylated alleles could be separated, and the ratio of the methylation was quantified. We found a clear correlation between the severity of the phenotype and lyso-Gb3 accumulation for heterozygous Fabry disease in females. Methylation of the non-mutated allele was also proportionately correlated to the clinical severity score measured by FASTEX.

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“…In the opinion of Authors, and based on the results of the ATTRACT study, given the possibility of oral therapy and its efficacy and safety, switching to migalastat can be considered in: (i) unstable patients with clinical evidence of progression of FD, in particular GI symptoms, cardiac hypertrophy and CNS events, (ii) patients with uncontrolled infusion reactions, (iii) patients with oor compliance to i.v. chronic infusions, as shown in the ATTRACT trial [15,52].…”

Section: Migalastat In Patients With Ert Failure/intolerancementioning

confidence: 86%

The GALA project: practical recommendations for the use of migalastat in clinical practice on the basis of a structured survey among Italian experts

Chimenti

Nencini

Pieruzzi

et al. 2020

Orphanet J Rare Dis

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Background: Oral migalastat has recently been approved for the treatment of Anderson-Fabry disease (FD) in patients aged ≥16 years with amenable mutations on the basis of two phase III trials, FACETS and ATTRACT. However, with the introduction of migalastat into clinical practice, it is important to correctly identify the patients who may gain the most benefits from this therapy. Due to the relatively recent availability of migalastat, its role in clinical practice still has to be included in guidelines or recommendations. On these bases, a multidisciplinary group of Italian Experts in the treatment of FD has run the GALA project, with the aim to collect the opinions of expert physicians and to propose some starting points for an experience-based use of migalastat. Results: Overall, although studies and data from longer-term follow-up with migalastat are still emerging, available evidence is consistent in showing that this molecule does represent a suitable therapy for the treatment of FD, in patients aged ≥16 years and with amenable mutations. The use of migalastat as an oral option appears to be overall safe, and experience thus far indicates potential for improving quality of life, controlling GI symptoms, stabilizing renal function and reducing cardiac hypertrophy. Conclusion: Migalastat can be considered either as a first-line therapygiven its efficacy, extensive tissue penetration, convenient oral regimen, and the current limited therapeutic options availableor in patients on enzyme-replacement therapy (ERT) who experience side effects, with poor compliance to chronic i.v. therapy, or with clinical evidence of progression of the disease.

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Safety of switching to Migalastat from enzyme replacement therapy in Fabry disease: Experience from the Phase 3 ATTRACT study

Cited by 13 publications

References 11 publications

Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data

Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data

Future clinical and biochemical predictions of Fabry disease in females by methylation studies of the GLA gene

The GALA project: practical recommendations for the use of migalastat in clinical practice on the basis of a structured survey among Italian experts

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