Lumasiran in the Management of Patients with Primary Hyperoxaluria Type 1: From Bench to Bedside

Figures & data

Table 1 Registered Preclinical and Clinical Trials Involving Lumasiran

Study Name	NCT Identifier	Phase	Status	Population	End Date
Study of lumasiran in healthy adults and patients with primary hyperoxaluria type 1	NCT02706886	I/II	Completed	Part A: Healthy subjects Part B:  ● Aged 6–64 years  ● 24-hour urinary oxalate excretion > 0.7 mmol/24 h per 1.73 m2 ● eGFR > 45 mL/min/1.73 m2	-
OLE	NCT03350451	II	Active, not recruiting	Adults and children affected by PH1	June 2023
ILLUMINATE-A	NCT03681184	III	Active, not recruiting	PH1 patients:  ● ≥ 6 years of age  ● eGFR ≥ 30 mL/min/1.73 m2	January 2024
ILLUMINATE-B	NCT03905694	III	Active, not recruiting	PH1 patients:  ● < 6 years of age  ● eGFR > 45 mL/min/1.73 m2 if ≥ 12 months of age  ● not abnormally high sCr if < 12 months of age	August 2024
ILLUMINATE-C	NCT04152200	III	Active, not recruiting	PH1 patients:  ● eGFR ≤ 45 mL/min/1.73 m^2 if ≥ 12 months of age  ● elevated sCr if < 12 months of age  ● stable hemodialysis allowed	July 2025
BONAPH1DE	NCT04982393	Prospective observational study	Recruiting	Patients diagnosed with PH1 will be managed and treated per routine clinical practice	September 2028

Table 2 Clinical Trials’ Most Relevant Results for Lumasiran

Clinical Trials	Results		AE**
	UOx*	POx*
ILLUMINATE-A	● Lumasiran determined a 65% mean reduction in UOx in treated patients vs 12% reduction in placebo patients ● 84% lumasiran-treated patients reached UOx at or < 1.5 x ULN^† (= 0.771 mmol/24 h/1.73m^2) vs 0% of placebo patients ● 52% of lumasiran-treated patients reached normal ranges of UOx vs 0% of placebo patients		No serious adverse events. The adverse events were mainly injection site reactions (erythema, pain, pruritus, swelling)
ILLUMINATE-B	● Lumasiran determined a 72% mean reduction in spot urinary oxalate: creatinine ratio ● 50% of lumasiran-treated patients reaching UOx at or < 1.5 x ULN^† ● 9% of lumasiran-treated patients reached UOx < ULN^†
ILLUMINATE-C		● 33% of reduction in POx* in cohort A (6 patients with advanced PH1 not on hemodialysis at study start) ● 42% of reduction in pre-hemodialysis POx in cohort B (15 PH1 patients on hemodialysis)	24% injection site reactions

Abbreviations: *UOx, urinary oxalate; Pox, plasma oxalate; **AE, adverse events; ^†ULN, upper limit of normal.

Table 3 Recommended Lumasiran Regimens Based on Body Weight, Currently Approved in the US and EU

Body Weight	Loading Dose	Maintenance Dose (Begin 1 Month After the Last Loading Dose)
Less than 10 kg	6 mg/kg once monthly for 3 doses	3 mg/kg once monthly
10 kg to less than 20 kg	6 mg/kg once monthly for 3 doses	6 mg/kg once every 3 months (quarterly)
20 kg and above	3 mg/kg once monthly for 3 doses	3 mg/kg once every 3 months (quarterly)