Long-term treatment for primary hyperoxaluria type 1 with lumasiran results in sustained reduction in urinary oxalate with acceptable safety through 24 months, investigators concluded in a presentation during the National Kidney Foundation’s 2022 Spring Clinical Meetings in Boston, Massachusetts.
Lumasiran, an RNA interference (RNAi) therapeutic that reduces oxalate excretion, was approved by the FDA on November 23, 2020 for the treatment of primary hyperoxaluria type 1, a rare genetic disorder that causes excess production of oxalate. Primary hyperoxaluria type 1 can lead to kidney stones and loss of kidney function.
John Lieske, MD, of Mayo Clinic in Rochester, Minnesota, and colleagues reported 24-month data from the ongoing ILLUMINATE-A phase 3, placebo-controlled trial. The trial enrolled 39 patients aged 6 years or older with genetically confirmed primary hyperoxaluria and an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m2 or higher. At the start of the trial, investigators randomly assigned 26 patients to receive lumasiran and 13 to receive placebo. The trial had a 6-month primary analysis period followed by an extension period of up to 54 months in which all patients received lumasiran.
At 6 months, 24 of the 26 patients in the lumasiran arm entered the extension period in which they continued to receive lumasiran (the lumasiran/lumasiran [L/L] group), and all 13 patients initially in the placebo arm crossed over to lumasiran (the placebo/lumasiran [P/L] group).
Patients in the L/L group had a sustained reduction in 24-hour urinary oxalate. Their mean 24-hour urinary oxalate reduction after 24 months of lumasarin treatment compared with baseline was 58%, Dr Lieske’s team reported in a poster presentation. In the P/L group, the mean 24-hour urinary oxalate reduction after 18 months of lumasarin treatment compared with baseline was 49%.
The proportion of patients achieving normalization or near normalization of urinary oxalate excretion was 83% of the L/L group after 24 months of lumasarin treatment and 62% of the P/L group after 18 months of lumasarin treatment.
The mean reductions from baseline in plasma oxalate at 24 months were 56% and 61%, respectively. The eGFR remained stable in both treatment arms.
In the L/L group, kidney stone event rates decreased from 3.19 per person-year during the 12 months prior to obtaining patients’ informed consent for the trial to 0.80 per person-year at 24 months. In the P/L group, the kidney stone event rates decreased from 0.54 to 0.28 per person-year.
Mild and transient injection-site reactions, abdominal pain, and headache were the most common adverse events related to lumasiran treatment.
Disclosure: This research was supported by Alnylam Pharmaceuticals. Please see the original reference for a full list of disclosures.
Lieske J, Groothoff JW, Frishberg Y, et al. Efficacy and safety of lumasiran in patients with primary hyperoxaluria type 1: 24-month analysis of the ILLUMINATE-A trial. Presented at the National Kidney Foundation’s 2022 Spring Clinical Meetings, Boston, Massachusetts, April 6-10, 2022. Poster 340.