Lumasiran: Dosing Administration Window

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The full Prescribing Information for OXLUMO® (lumasiran) is provided here. Alnylam Pharmaceuticals does not recommend the use of its products in any manner that is inconsistent with the approved Prescribing Information. This resource may contain information that is not in the approved Prescribing Information.

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SUMMARY

The recommended dosing regimen of lumasiran consists of monthly loading doses for 3 doses, followed by maintenance doses beginning 1 month after the last loading dose. Lumasiran is administered subcutaneously, and dosing is based on actual body weight.1

In the ILLUMINATE-A study, patients were randomized to receive either lumasiran or placebo loading doses once monthly for 3 doses, followed by maintenance doses every 3 months beginning 1 month after the last loading dose.2,3 After receiving the first loading dose of lumasiran, the second and third loading doses as well as the first maintenance dose were administered within a ±4 day dosing window during 6-month double-blind treatment period for patients initially randomized to lumasiran and during the 3-month blinded treatment extension period for patients initially receiving placebo. In the OLE period, doses from Month 12 through the end of the study were to be administered within a ±28 day dosing window.3
In the ILLUMINATE-B study, patients received lumasiran once monthly for 3 doses at a dose based on body weight category, followed by maintenance doses once monthly (patients weighing <10 kg) or once every 3 months (patients weighing ≥10 kg) beginning at Month 3.4,5 The second loading dose at Month 1, the third loading dose at Month 2, and doses from Month 3 through Month 6 were to be administered within a ±14 day dosing window. During the 54-month extension period, doses were to be administered within a ±14 day dosing window for patients weighing <10 kg or within a ±28 day dosing window for patients weighing ≥10 kg.5
In the ILLUMINATE-C study, patients received lumasiran once monthly (±14 days) for 3 doses at a dose based on body weight category, followed by maintenance doses once monthly (patients weighing <10 kg) or once every 3 months (patients weighing ≥10 kg) beginning at Month 3. Doses through Month 6 were to be administered within a ±14 day dosing window. Ongoing doses from Month 7 to the end of the study were to be administered once monthly (±14 days) in patients who weighed <10 kg or every 3 months (±28 days) in patients who weighed ≥10 kg.6,7

INDEX

Clinical Data – Label Information – Abbreviations – References

clinical data

ILLUMINATE-A

ILLUMINATE-A was a phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of lumasiran in adults and children ≥6 years old with PH1 and an eGFR ≥30 mL/min/1.73m2. Patients were randomized (2:1) to receive subcutaneous injections of lumasiran 3 mg/kg (N=26) or placebo (N=13) once monthly for 3 loading doses, followed by maintenance doses once every 3 months beginning 1 month after the last loading dose. The primary endpoint was the percent change from baseline in 24-hour UOx excretion corrected for BSA at 6 months (average of visits from Month 3 through 6). After the 6-month double-blind treatment period, all patients received lumasiran in an optional 54-month OLE.2 Of the 39 patients enrolled, 13 of the 13 in the placebo crossover arm and 24 of the 26 in the continuous lumasiran group completed treatment in the 54-month OLE.8

During the 6-month double-blind treatment period, patients were randomized (2:1) to receive loading doses of 3.0 mg/kg of lumasiran or placebo once monthly for 3 doses, followed by maintenance doses of 3.0 mg/kg of lumasiran every 3 months beginning 1 month after the last loading dose.2,3

For patients who received placebo during the double-blind period, a 3-month blinded treatment extension period enabled the transition to initiate lumasiran while investigators and patients remained blinded to the earlier double-blind period treatment assignment. For this reason, during the 3-month blinded treatment extension period, patients who had been randomized to lumasiran also received 2 monthly doses of placebo, so that all patients received blinded monthly treatment during this period (administered at the Month 6, 7, and 8 visits). At the Month 9 visit, all patients received their first open-label maintenance dose of lumasiran, marking the beginning of the OLE period, and lumasiran was administered every 3 months thereafter.9

After receiving the first loading dose of lumasiran, the second and third loading doses as well as the first maintenance dose were administered within a ±4 day dosing window during 6-month double-blind treatment period for patients initially randomized to lumasiran and during the 3-month blinded treatment extension period for patients initially receiving placebo. In the OLE period, doses from Month 12 through the end of the study were to be administered within a ±28 day dosing window.3

ILLUMINATE-B

ILLUMINATE-B (N=18) was a phase 3, open-label, single-arm study with a 6-month primary analysis period followed by an ongoing 54-month extension period to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in infants and young children <6 years old with PH1 and an eGFR >45 mL/min/1.73m2 (or normal serum creatinine for infants <12 months old). Patients received subcutaneous injections of lumasiran as determined by a body weight-based dosing regimen. The primary endpoint was the percent change from baseline in spot UOx:Cr at 6 months.4

During the 6-month treatment period, patients received loading doses of lumasiran once monthly for 3 doses at a dose based on body weight category, followed by maintenance doses once monthly (patients weighing <10 kg) or once every 3 months (patients weighing ≥10 kg) beginning at Month 3. Doses of lumasiran were required to be administered at least 21 days apart.4,5

The second loading dose at Month 1, the third loading dose at Month 2, and doses from Month 3 through Month 6 were to be administered within a ±14 day dosing window. During the 54-month extension period, doses were to be administered within a ±14 day dosing window for patients weighing <10 kg or within a ±28 day dosing window for patients weighing ≥10 kg.5

ILLUMINATE-C

ILLUMINATE-C was a phase 3, open-label, single-arm study with a 6-month primary analysis period followed by an ongoing 54-month extension period to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in full term infants to adult patients with advanced kidney disease with an eGFR ≤45 mL/min/1.73m2 (or elevated serum creatinine if <12 months old) and POx ≥20 µmol/L. Patients enrolled in the study included those not receiving hemodialysis in Cohort A (N=6) and those receiving hemodialysis in Cohort B (N=15). Patients received subcutaneous injections of lumasiran as determined by a body weight-based dosing regimen. The primary endpoints were the percent change from baseline in POx at 6 months (Cohort A) and percent change from baseline in predialysis POx at 6 months (Cohort B).6

During the 6-month primary analysis period, patients received loading doses of lumasiran once monthly (±14 days) for 3 doses at a dose based on body weight category, followed by maintenance doses once monthly (patients weighing <10 kg) or once every 3 months (patients weighing ≥10 kg) beginning at Month 3. Doses through Month 6 were to be administered within a ±14 day dosing window. Ongoing doses from Month 7 to the end of the study were to be administered once monthly (±14 days) in patients who weighed <10 kg or every 3 months (±28 days) in patients who weighed ≥10 kg. Doses of lumasiran were required to be administered at least 21 days apart.6,7

Oxlumo prescribing information – Relevant content

The DOSAGE AND ADMINISTRATION section provides the following information1:

Recommended Dosage

The recommended dosing regimen of OXLUMO consists of loading doses (monthly for 3 doses) followed by maintenance doses (beginning 1 month after the last loading dose) administered subcutaneously as shown in Table 1.

Dosing is based on actual body weight.

Table 1. OXLUMO Weight-Based Dosing Regimen

Body Weight	Loading Dose	Maintenance Dose (the maintenance dose should begin one month after the last loading does)
Less than 10 kg	6 mg/kg once monthly for 3 doses	3 mg/kg once monthly, beginning 1 month after the last loading dose
10 kg to less than 20 kg	6 mg/kg once monthly for 3 doses	6 mg/kg once every 3 months (quarterly), beginning 1 month after the last loading dose
20 kg and above	3 mg/kg once monthly for 3 doses	3 mg/kg once every 3 months (quarterly), beginning 1 month after the last loading dose

Missed Dose

If a dose is delayed or missed, administer OXLUMO as soon as possible. Resume prescribed monthly or quarterly dosing, from the most recently administered dose.

Abbreviations

BSA = body surface area; eGFR = estimated glomerular filtration rate; OLE = open label extension; PH1 = primary hyperoxaluria type 1; POx = plasma oxalate; UOx = urinary oxalate; UOx:Cr = urinary oxalate:creatinine ratio.

Updated 13 December 2024

References

1. OXLUMO (lumasiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals.

2. Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021;384(13):1216-1226. doi:10.1056/NEJMoa2021712

3. Alnylam Pharmaceuticals. Data on file. MED-ALL-GO1-2000101.

4. Frishberg Y, Hayes W, Shasha-Lavsky H, et al. Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 30-month analysis of the phase 3 ILLUMINATE-B trial. Front Pediatr. 2024;12. doi:10.3389/fped.2024.1392644

5. Alnylam Pharmaceuticals. Data on file. MED-ALL-GO1-2000064.

6. Michael M, Groothoff JW, Shasha-Lavsky H, et al. Lumasiran for advanced primary hyperoxaluria type 1: phase 3 ILLUMINATE-C trial. Am J Kidney Dis. 2023;81(2):145-155. doi:10.1053/j.ajkd.2022.05.012

7. Supplement to: Michael M, Groothoff JW, Shasha-Lavsky H, et al. Lumasiran for advanced primary hyperoxaluria type 1: phase 3 ILLUMINATE-C trial. Am J Kidney Dis. 2023;81(2):145-155. doi:10.1053/j.ajkd.2022.05.012

8. Saland JM, Lieske JC, Willey R, et al. Long-term efficacy and safety of lumasiran in patients with primary hyperoxaluria type 1: Final analysis of the ILLUMINATE-A trial. Presented at: American Society of Nephrology (ASN) Kidney Week; October 24-27, 2024; San Diego, CA, USA.

9. Supplement to: Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021;384(13):1216-1226. doi:10.1056/NEJMoa2021712


MED-ALL-GO1-2300043 3.0 Approved through Dec 2026

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