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Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children

Publication Details

Genetics in Medicine

December 2021

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Author(s)

David J Sas¹, Daniella Magen², Wesley Hayes³, Hadas Shasha-Lavsky⁴, Mini Michael⁵, Indra Schulte⁶, Anne-Laure Sellier-Leclerc⁷, Jiandong Lu⁸, Ali Seddighzadeh⁸, Bahru Habtemariam⁸, Tracy L McGregor⁸, Kenji P Fujita⁸, Yaacov Frishberg⁹; ILLUMINATE-B Workgroup

Affiliations

¹Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, MN; ²Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel; ³Department of Paediatric Nephrology, Great Ormond Street Hospital, London, United Kingdom; ⁴Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel; ⁵Division of Pediatric Nephrology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, TX; ⁶Department of Pediatric Nephrology, University of Bonn, Bonn, Germany; ⁷Hôpital Femme Mère Enfant and Centre d'Investigation Clinique Inserm, Hospices Civils de Lyon, ERKnet, Bron, France; ⁸Alnylam Pharmaceuticals, Cambridge, MA; ⁹Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

Abstract

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.

Conclusions:

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.