TY - JOUR
T1 - Phase 3 trial of lumasiran for primary hyperoxaluria type 1
T2 - A new RNAi therapeutic in infants and young children
AU - ILLUMINATE-B Workgroup
AU - Sas, David J.
AU - Magen, Daniella
AU - Hayes, Wesley
AU - Shasha-Lavsky, Hadas
AU - Michael, Mini
AU - Schulte, Indra
AU - Sellier-Leclerc, Anne Laure
AU - Lu, Jiandong
AU - Seddighzadeh, Ali
AU - Habtemariam, Bahru
AU - McGregor, Tracy L.
AU - Fujita, Kenji P.
AU - Frishberg, Yaacov
AU - Bacchetta, Justine
AU - Baudouin, Véronique
AU - Becker-Cohen, Rachel
AU - Tzvi Behr, Shimrit
AU - Ben-Shalom, Efrat
AU - Berdaguer, Maria
AU - Bockenhauer, Detlef
AU - Cochat, Pierre
AU - Coenen, Martin
AU - Cramer, Carl H.
AU - Deschênes, Georges
AU - Dossier, Claire
AU - Doye, Emilie
AU - Feldman, Liat Feraru
AU - Hohenadel, Maximilian
AU - Kaguelidou, Florentia
AU - Zebegret, Irina Libinson
AU - Lieske, John C.
AU - Maisin, Anne
AU - Milliner, Dawn S.
AU - Plonsky Toder, Moran
AU - Pollack, Shirley
AU - Portefaix, Aurélie
AU - Ranchin, Bruno
AU - Rinat, Choni
AU - Safdar, Adnan
AU - Schalk, Gesa
AU - Srivaths, Poyyapakkam R.
AU - Tran, Cheryl L.
AU - Van't Hoff, William
AU - Weinbrand-Goichberg, Jenny
AU - Weissman, Irith
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - Purpose: Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1. Methods: This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an estimated glomerular filtration rate >45 mL/min/1.73 m2, if aged ≥12 months, or normal serum creatinine, if aged <12 months. The primary end point was percent change in spot urinary oxalate to creatinine ratio (UOx:Cr) from baseline to month 6. Secondary end points included proportion of patients with urinary oxalate ≤1.5× upper limit of normal and change in plasma oxalate. Results: All patients (N = 18) completed the 6-month primary analysis period. Median age at consent was 50.1 months. Least-squares mean percent reduction in spot UOx:Cr was 72.0%. At month 6, 50% of patients (9/18) achieved spot UOx:Cr ≤1.5× upper limit of normal. Least-squares mean percent reduction in plasma oxalate was 31.7%. The most common treatment-related adverse events were transient, mild, injection-site reactions. Conclusion: Lumasiran showed rapid, sustained reduction in spot UOx:Cr and plasma oxalate and acceptable safety in patients aged <6 years with PH1, establishing RNA interference therapies as safe, effective treatment options for infants and young children.
AB - Purpose: Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1. Methods: This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an estimated glomerular filtration rate >45 mL/min/1.73 m2, if aged ≥12 months, or normal serum creatinine, if aged <12 months. The primary end point was percent change in spot urinary oxalate to creatinine ratio (UOx:Cr) from baseline to month 6. Secondary end points included proportion of patients with urinary oxalate ≤1.5× upper limit of normal and change in plasma oxalate. Results: All patients (N = 18) completed the 6-month primary analysis period. Median age at consent was 50.1 months. Least-squares mean percent reduction in spot UOx:Cr was 72.0%. At month 6, 50% of patients (9/18) achieved spot UOx:Cr ≤1.5× upper limit of normal. Least-squares mean percent reduction in plasma oxalate was 31.7%. The most common treatment-related adverse events were transient, mild, injection-site reactions. Conclusion: Lumasiran showed rapid, sustained reduction in spot UOx:Cr and plasma oxalate and acceptable safety in patients aged <6 years with PH1, establishing RNA interference therapies as safe, effective treatment options for infants and young children.
KW - Infants
KW - Lumasiran
KW - PH1
KW - RNAi
KW - Young children
UR - http://www.scopus.com/inward/record.url?scp=85121488214&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2021.10.024
DO - 10.1016/j.gim.2021.10.024
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C2 - 34906487
AN - SCOPUS:85121488214
SN - 1098-3600
VL - 24
SP - 654
EP - 662
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 3
ER -