Publications

The material below is provided to support scientific exchange. Any content about investigational therapeutics or investigational uses of locally approved products does not establish the safety or efficacy of these therapeutics or uses, and there is no guarantee of local regulatory approval.

For questions beyond a product’s authorized indications or for information not available here, please contact Alnylam Medical Information.

Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial

Publication Details

American Journal of Kidney Diseases

July 2022

Access Here

Author(s)

Mini Michael¹, Jaap W Groothoff², Hadas Shasha-Lavsky³, John C Lieske⁴, Yaacov Frishberg⁵, Eva Simkova⁶, Anne-Laure Sellier-Leclerc⁷, Arnaud Devresse⁸, Fitsum Guebre-Egziabher⁹, Sevcan A Bakkaloglu¹⁰, Chebl Mourani¹¹, Rola Saqan¹², Richard Singer¹³, Richard Willey¹⁴, Bahru Habtemariam¹⁴, John M Gansner¹⁴, Ishir Bhan¹⁴, Tracy McGregor¹⁴, Daniella Magen¹⁵

Affiliations

¹Division of Pediatric Nephrology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas; ²Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; ³Pediatric Nephrology Unit, Galilee Medical Center, Azrieli Faculty of Medicine, Bar Ilan University, Nahariya, Israel; ⁴Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; ⁵Division of Pediatric Nephrology, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; ⁶Nephrology - Medical Affairs, Al Jalila Children's Hospital, Dubai, United Arab Emirates; ⁷Hôpital Femme Mère Enfant en Centre d'Investigation Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon, ERKnet, Bron, France; ⁸Division of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; ⁹Nephrology and Renal Function Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, INSERM 1060, Lyon, France; ¹⁰Department of Pediatric Nephrology, Faculty of Medicine, Gazi University, Ankara, Turkey; ¹¹Department of Pediatrics, Hôtel-Dieu de France Hospital, Beirut, Lebanon; ¹²Pharmaceutical Research Center, Jordan University of Science and Technology, Irbid, Jordan; ¹³Renal Service, Canberra Health Services, Garran, ACT, Australia; ¹⁴Alnylam Pharmaceuticals, Cambridge, Massachusetts; ¹⁵Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel

Abstract

Rationale & Objective:

Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.

Outcome:

Primary end point: percent change in POx from baseline to month 6 (cohort A; not receiving hemodialysis at enrollment) and percent change in predialysis POx from baseline to month 6 (cohort B; receiving hemodialysis at enrollment). Pharmacodynamic secondary end points: percent change in POx area under the curve between dialysis sessions (cohort B only); absolute change in POx; percent and absolute change in spot urinary oxalate-creatinine ratio; and 24-hour urinary oxalate adjusted for body surface area.

Results:

All patients (N = 21; 43% female; 76% White) completed the 6-month primary analysis period. Median age at consent was 8 (range, 0-59) years. For the primary end point, least-squares mean reductions in POx were 33.3% (95% CI, −15.2% to 81.8%) in cohort A (n = 6) and 42.4% (95% CI, 34.2%-50.7%) in cohort B (n = 15). Improvements were also observed in all pharmacodynamic secondary end points. Most adverse events were mild or moderate. No patient discontinued treatment or withdrew from the study. The most commonly reported lumasiran-related adverse events were injection-site reactions, all of which were mild and transient.

Conclusions:

Lumasiran resulted in substantial reductions in POx with acceptable safety in patients with PH1 who have advanced kidney disease, supporting its efficacy and safety in this patient population.