Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication OXLUMO is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients [see Clinical Pharmacology (12.1) , Clinical Studies (14.1 , 14.2 , 14.3) ] . FDA label
Also known as ALN-GO1, OXLUMO
Lumasiran · 6 trials · 12 indications
Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.
Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort B, the baseline is defined as the mean of the last four pre-dialysis plasma oxalate samples collected prior to the first dose of lumasiran. In Cohort B, only pre-dialysis samples are utilized.
Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.
Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.
The primary endpoint is the percentage change in pre-dialysis plasma oxalate levels in non-primary hyperoxaluria patients with raised plasma oxalate levels who are receiving maintenance haemodialysis.
AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety analysis set included all participants who received any amount of study drug.
An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
| Arm | Type | Description |
|---|---|---|
| Lumasiran | EXPERIMENTAL | All patients will receive open-label lumasiran. |
| Placebo/Lumasiran | PLACEBO_COMPARATOR | Lumasiran-matching placebo (normal saline \[0.9% NaCl\]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period. |
| Lumasiran/Lumasiran | EXPERIMENTAL | Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period. |
| Lumasiran, treatment arm | EXPERIMENTAL | Treatment arm with Lumasiran |
| Placebo | PLACEBO_COMPARATOR | Placebo injection with 0.9% sodium chloride |
| Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M | EXPERIMENTAL | Participants enrolling from study 001B (NCT02706886), received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months \[Q3M\]) from Day 1 up to a maximum of Month 6. By Month 6, all participants were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 participants who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM \& 3 mg/kg Q3M, these participants were pooled into one arm as recommended by the Safety Review Committee (SRC). |
| Lumasiran (ALN-GO1): 3.0 mg/kg QM | EXPERIMENTAL | Participants enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all participants were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. |
| Part A: SAD: Placebo | PLACEBO_COMPARATOR | A single dose of matching placebo will be administered subcutaneously (SC). |
| Part A: SAD: Lumasiran 0.3 mg/kg | EXPERIMENTAL | A single dose of 0.3 mg/kg lumasiran will be administered SC. |
| Part A: SAD: Lumasiran 1.0 mg/kg | EXPERIMENTAL | A single dose of 1.0 mg/kg lumasiran will be administered SC. |
| Part A: SAD: Lumasiran 3.0 mg/kg | EXPERIMENTAL | A single dose of 3.0 mg/kg lumasiran will be administered SC. |
| Part A: SAD: Lumasiran 6.0 mg/kg | EXPERIMENTAL | A single dose of 6.0 mg/kg lumasiran will be administered SC. |
| Part B: MAD: Placebo | PLACEBO_COMPARATOR | Participants with primary hyperoxaluria type 1 (PH1) will be treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo treated participants will cross over to their respective Part B lumasiran arms in the Part B: MAD Study Day 85-End of Study Period and will then be treated with lumasiran. The estimated total time on study was up to 546 days. |
| Part B: MAD: Lumasiran 1.0 mg/kg qM | EXPERIMENTAL | Participants with PH1 will be treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
| Part B: MAD: Lumasiran 3.0 mg/kg qM | EXPERIMENTAL | Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
| Part B: MAD: Lumasiran 3.0 mg/kg q3M | EXPERIMENTAL | Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
| Name | Type | Description |
|---|---|---|
| Lumasiran | DRUG | Lumasiran will be administered by subcutaneous (SC) injection. |
| Placebo | DRUG | Placebo by SC injection |
| 0.9% Sodium Chloride (placebo) | DRUG | Placebo, subcutaneous injection, given as three monthly loading doses followed by one further maintenance dose. |
Inclusion Criteria: * Has documented diagnosis of primary hyperoxaluria type 1 (PH1) * Estimated glomerular filtration rate (eGFR) ≤45 mL/min/1.73 m\^2 for patients ≥12 months of age (\<12 months of age, must have serum creatinine considered elevated for age) * Meets plasma oxalate level requiremen...
Lumasiran is an RNA therapy developed for primary hyperoxaluria type 1 (PH1), a rare inherited disorder, and is also being studied in hyperoxalaemic patients on haemodialysis. Its clinical program covers primary hyperoxaluria, PH1, and haemodialysis-related hyperoxalemia, with a focus on reducing oxalate burden in these patient populations.
Lumasiran targets HAO1, the gene encoding glycolate oxidase, and acts as an RNAi inhibitor. By targeting HAO1, it is designed to reduce the production of oxalate, the toxic metabolite that accumulates in primary hyperoxaluria type 1 and drives kidney and cardiovascular complications in affected patients.
Lumasiran is developed by Alnylam Pharmaceuticals, Inc., which trades under the ticker ALNY. Alnylam is the sponsor of the clinical program evaluating lumasiran across primary hyperoxaluria type 1 and hyperoxalaemia in haemodialysis patients.
Lumasiran is in Phase 2 development for its haemodialysis indication, with a recruiting Phase 2 trial in hyperoxalaemic patients on haemodialysis. The primary hyperoxaluria type 1 program has completed Phase 3 studies, including trials in infants, children, and adults. Lumasiran is an investigational RNA therapy.
Lumasiran has been studied in three completed Phase 3 trials in primary hyperoxaluria type 1: NCT04152200 in advanced PH1, NCT03905694 in infants and young children, and NCT03681184 in children and adults. A Phase 2 trial, NCT06225544, is recruiting hyperoxalaemic patients on haemodialysis in Germany.
Across the reported trials, 112 patients have been enrolled in lumasiran studies. This includes 50 patients in the recruiting Phase 2 haemodialysis trial NCT06225544, 21 in NCT04152200, 18 in NCT03905694, and 39 in NCT03681184. The trials are randomized, double-blind, and placebo-controlled.