Lumasiran: Dosing Regimen

Lumasiran: Dosing Regimen

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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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INDEX

Label Information – Clinical Data – Abbreviations – References

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

For Patients on Hemodialysis

Administer OXLUMO after hemodialysis if administered on dialysis days.

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.

Clinical Data

Phase 1/2 Study

The Phase 1/2 study was a single-blind, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamics of subcutaneously administered lumasiran in healthy adult subjects (Part A) and patients with PH1 (Part B).2

• In Part A of the study, 32 healthy volunteers were randomized to receive a single SC dose of lumasiran 0.3 mg/kg (n=6), 1.0 mg/kg (n=6), 3.0 mg/kg (n=6), 6.0 mg/kg (n=6), or placebo (n=8).2
• In Part B of the study, patients with PH1 were randomized (3:1) to receive multiple doses of placebo (n=3), 1.0 mg/kg of lumasiran every 28 days for 3 doses (n=3), 3.0 mg/kg every 28 days for 3 doses (n=3), or 3.0 mg/kg every 84 days for 2 doses (n=3).2
• The OLE cohorts received doses of lumasiran at a dosage of 1.0 mg/kg every 28 days for 3 doses (n=4) or 3.0 mg/kg every 28 days for 3 doses (n=4).2

Doses of lumasiran demonstrated rapid and sustained reduction of UOx levels in patients with PH1 at doses of 1.0 mg/kg monthly, 3.0 mg/kg monthly, and 3.0 mg/kg once every 3 months. Results from the Phase 1/2 study demonstrated a more rapid and higher magnitude of UOx reduction relative to baseline in the 3 mg/kg monthly cohort compared to other cohorts. This allowed for an earlier steady state pharmacodynamic effect and led to the dose selection of the lumasiran Phase 3 clinical studies. All 20 patients enrolled in the Phase 1/2 Part B arm of the study completed the study and enrolled in the OLE.2

Phase 2 OLE Study

The Phase 2 OLE study was a multicenter, open-label, extension study to evaluate the long-term safety and tolerability of lumasiran in patients with PH1. Patients with PH1 previously dosed in the Phase 1/2 parent study were eligible to enroll in the Phase 2 OLE study.2,3

At the start of the study, patients received their original dose of lumasiran from the Phase 1/2 study. All patients were transitioned to the maintenance dose regimen of 3.0 mg/kg every 3 months following the completion of the patient’s respective starting doses.3

ILLUMINATE-A Study

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. After the 6-month double-blind treatment period, all patients received lumasiran in an optional 54-month OLE.4

During the 6-month double-blind treatment period, 39 patients were randomized (2:1) to receive loading doses of 3.0 mg/kg of lumasiran (n=26) or placebo (n=13) as a subcutaneous injection once monthly for 3 doses, followed by a maintenance dose of 3.0 mg/kg of lumasiran 1 month after the last loading dose. Patients that were originally randomized to the placebo arm received loading doses of 3.0 mg/kg of lumasiran at Months 6, 7, and 8 study visits during the extension period.4,5

ILLUMINATE-B Study

ILLUMINATE-B was a phase 3, open-label, single-arm study with a 6-month primary analysis period followed by a 54-month extended dosing period to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in full term 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).6

During the 6-month treatment period, 18 patients received loading doses (weight dependent) of lumasiran once monthly for 3 doses, followed by a maintenance dose once monthly or once every 3 months as recommended by weight-based dosing (Table 1).6 Continued weight-based dosing utilized the patient’s weight that was obtained 7 days prior to dosing during the extension period.7

ILLUMINATE-C Study

The ILLUMINATE-C study 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 PH1 with an eGFR ≤45 mL/min/1.73m2 (or elevated serum creatinine if <12 months old) and POx ≥20 µmol/L. Patients (N=21) enrolled in the study included those not receiving hemodialysis in Cohort A (N=6) and those receiving hemodialysis in Cohort B (N=15).8

Patients received loading doses (weight dependent) of lumasiran once monthly for 3 doses, followed by a maintenance dose once monthly or once every 3 months as recommended by weight-based dosing (Table 1). In patients on dialysis, lumasiran was administered no later than 120 minutes after receiving dialysis.8

Abbreviations

eGFR = estimated glomerular filtration rate; OLE = open-label extension; PH1 = primary hyperoxaluria type 1; POx = plasma oxalate; SC = subcutaneous; UOx = urinary oxalate.

Updated 04 November 2024

References

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

2.  Frishberg Y, Deschenes G, Groothoff JW, et al. Phase 1/2 study of lumasiran for treatment of primary hyperoxaluria type 1: a placebo-controlled randomized clinical trial. CJASN. 2021;16(7):1025-1036. doi:10.2215/CJN.14730920

3.  Frishberg Y, Groothoff JW, Hulton SA, et al. Long-term treatment with lumasiran: Final results from the phase 2 open-label extension study. Presented at: European Renal Association (ERA) Congress; May 23-26, 2024; Stockholm, Sweden.

4.  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

5.  Protocol for: 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

6.  Hayes W, Sas DJ, Magen D, et al. Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial. Pediatr Nephrol. 2023;38(4):1075-1086. doi:10.1007/s00467-022-05684-1

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

8.  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