Agalsidase beta
Sources réglementaires consultées
Contre-indications
Absolues
- Hypersensibilité potentiellement mortelle, y compris l’anaphylaxie, au produit ou à ses composants.
Mises en garde cliniques
- Mise en garde encadrée · Avertissement encadre: des reactions d'hypersensibilite, y compris l'anaphylaxie, et des reactions liees a la perfusion sont survenues; commencer dans un etablissement de sante disposant d'un soutien de reanimation. — FDA FABRAZYME prescribing information
- Mise en garde majeure · Des anticorps peuvent apparaitre; les patients ayant une maladie renale avancee ou une atteinte cardiaque necessitent une surveillance etroite selon la notice. — FDA FABRAZYME prescribing information
Interactions médicamenteuses
- SévèreChloroquine, amiodarone, benzoquinone ou gentamicine
Mécanisme: Eviter la coadministration en raison d'un risque theorique d'inhibition de l'activite intracellulaire de l'alpha-galactosidase A.
Recommandation: La coadministration requiert l'evaluation de l'equipe soignante.
CIMA AEMPS FT_01188001
Grossesse et allaitement
Pendant la grossesse, n'utiliser que si cela est clairement necessaire; pendant l'allaitement, decider avec l'equipe soignante d'interrompre l'allaitement ou le traitement.
Bibliographie récente (PubMed)
Fabry disease (FD) is an inherited lysosomal storage disorder, leading to multisystemic manifestations and causing significant morbidity and mortality. The aim of this narrative review is to present the current and novel therapeutic strategies in FD, including symptomatic and specific treatment options. A systematic literature search was conducted to identify relevant studies, including completed and ongoing randomized-controlled clinical trials (RCTs), prospective or retrospective cohort studies, case series and case reports that provided clinical data regarding FD treatment. A multidisciplinary symptomatic treatment is recommended for FD patients, personalized according to disease manifestations and their severity. During the last two decades, FD-specific treatments, including two enzyme-replacement-therapies (agalsidase alfa and agalsidase beta) and chaperone treatment with migalastat have been approved for use and allowed for symptoms' stabilization or even disease burden reduction. More therapeutic agents are currently under investigation. Substrate reduction therapies, including lucerastat and venglustat, have shown promising results in RCTs and may be used either as monotherapy or as complementary therapy to established enzymereplacement- therapies. More stable enzyme-replacement-therapy molecules that are associated with less adverse events and lower likelihood of neutralizing antibodies formation have also been developed. Ex-vivo and in-vivo gene therapy is being tested in animal models and pilot human clinical trials, with preliminary results showing a favorable safety and efficacy profile. The therapeutic landscape in FD appears to be actively expanding with more treatment options expected to become available in the near future, allowing for a more personalized approach in FD patients.
Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. NCT02795676.
Fabry disease is a rare but life-threatening, X-linked, inherited lysosomal storage disorder in which globotriaosylceramide is insufficiently metabolized because of reduced α-galactosidase A activity. Cellular globotriaosylceramide accumulation causes a multisystemic disease, which, if left untreated, reduces life expectancy in female and male individuals by around 10 and 20 years, respectively, leading to progressive renal failure, hypertrophic cardiomyopathy, cardiac arrhythmia, and premature cerebral infarction. The method of choice for confirming the diagnosis is the determination of reduced α-galactosidase A activity in leukocytes in male individuals and the molecular genetic detection of a disease-causing mutation in female individuals. Current approved treatment includes enzyme replacement therapy (agalsidase alfa [0.2 mg/kg body weight], agalsidase beta or pegunigalsidase alfa [both 1.0 mg/kg body weight]) every other week intravenously or, if a responding ('amenable') α-galactosidase A mutation is present, oral pharmacological chaperone therapy (migalastat 123 mg, every other day). Future therapeutic options may include substrate reduction therapy, gene therapy, messenger RNA therapy, and/or vesicle-packaged enzyme replacement therapy. This review presents current and future treatment options with advantages and disadvantages of the different treatment options.