• Je něco špatně v tomto záznamu ?

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies

M. Holida, A. Linhart, A. Pisani, N. Longo, F. Eyskens, O. Goker-Alpan, E. Wallace, P. Deegan, C. Tøndel, U. Feldt-Rasmussen, D. Hughes, A. Sakov, R. Rocco, EB. Almon, S. Alon, R. Chertkoff, DG. Warnock, S. Waldek, WR. Wilcox, JA. Bernat

. 2025 ; 48 (1) : e12795. [pub] 20241009

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, klinické zkoušky, fáze III, multicentrická studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc25002910

Grantová podpora
Protalix Biotherapeutics

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25002910
003      
CZ-PrNML
005      
20250206103936.0
007      
ta
008      
250121s2025 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1002/jimd.12795 $2 doi
035    __
$a (PubMed)39381863
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Holida, Myrl $u Division of Medical Genetics and Genomics, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
245    12
$a A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies / $c M. Holida, A. Linhart, A. Pisani, N. Longo, F. Eyskens, O. Goker-Alpan, E. Wallace, P. Deegan, C. Tøndel, U. Feldt-Rasmussen, D. Hughes, A. Sakov, R. Rocco, EB. Almon, S. Alon, R. Chertkoff, DG. Warnock, S. Waldek, WR. Wilcox, JA. Bernat
520    9_
$a Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a mladý dospělý $7 D055815
650    12
$a alfa-galaktosidasa $x aplikace a dávkování $x terapeutické užití $7 D000519
650    _2
$a rozvrh dávkování léků $7 D004334
650    12
$a enzymová substituční terapie $x metody $7 D056947
650    12
$a Fabryho nemoc $x farmakoterapie $7 D000795
650    _2
$a polyethylenglykoly $x aplikace a dávkování $7 D011092
650    12
$a rekombinantní proteiny $x aplikace a dávkování $x terapeutické užití $7 D011994
650    _2
$a sfingolipidy $x krev $7 D013107
650    _2
$a výsledek terapie $7 D016896
650    _2
$a trihexosylceramidy $x krev $7 D014281
655    _2
$a časopisecké články $7 D016428
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Linhart, Aleš $u Charles University, General University Hospital, Prague, Czech Republic
700    1_
$a Pisani, Antonio $u Department of Public Health, University Federico II of Naples, Naples, Italy
700    1_
$a Longo, Nicola $u Pediatrics Medical Genetics, University of Utah, Salt Lake City, Utah, USA
700    1_
$a Eyskens, François $u Antwerp University Hospital UZA, Edegem, Belgium
700    1_
$a Goker-Alpan, Ozlem $u Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, Virginia, USA
700    1_
$a Wallace, Eric $u University of Alabama at Birmingham, Birmingham, Alabama, USA
700    1_
$a Deegan, Patrick $u Lysosomal Disorders Unit, Cambridge University Hospitals NHS Foundation Trust and University of Cambridge, Cambridge, UK
700    1_
$a Tøndel, Camilla $u University of Bergen and Haukeland University Hospital, Bergen, Norway
700    1_
$a Feldt-Rasmussen, Ulla $u Department of Endocrinology and Metabolism, Rigshospitalet and Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
700    1_
$a Hughes, Derralynn $u LSDU, Royal Free London NHS Foundation Trust, and University College London, London, UK
700    1_
$a Sakov, Anat $u DataSights Ltd, Haifa, Israel
700    1_
$a Rocco, Rossana $u Chiesi Farmaceutici S.p.A, Parma, Italy
700    1_
$a Almon, Einat Brill $u Department of Product Development, Protalix Biotherapeutics, Carmiel, Israel
700    1_
$a Alon, Sari $u Department of Product Development, Protalix Biotherapeutics, Carmiel, Israel
700    1_
$a Chertkoff, Raul $u Department of Product Development, Protalix Biotherapeutics, Carmiel, Israel
700    1_
$a Warnock, David G $u University of Alabama at Birmingham, Birmingham, Alabama, USA
700    1_
$a Waldek, Stephen $u University of Sunderland, Sunderland, UK
700    1_
$a Wilcox, William R $u Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
700    1_
$a Bernat, John A $u Division of Medical Genetics and Genomics, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA $1 https://orcid.org/0000000320336129
773    0_
$w MED00002747 $t Journal of inherited metabolic disease $x 1573-2665 $g Roč. 48, č. 1 (2025), s. e12795
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39381863 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250121 $b ABA008
991    __
$a 20250206103931 $b ABA008
999    __
$a ok $b bmc $g 2262979 $s 1238917
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2025 $b 48 $c 1 $d e12795 $e 20241009 $i 1573-2665 $m Journal of inherited metabolic disease $n J Inherit Metab Dis $x MED00002747
GRA    __
$p Protalix Biotherapeutics
LZP    __
$a Pubmed-20250121

Najít záznam

Citační ukazatele

Možnosti archivace