Treatment Proves Highly Effective for Primary Hyperoxaluria Type 1

Lumasiran was very effective in improving levels of oxalate in a patient with primary hyperoxaluria type 1, a rare genetic disease. Findings were published in Frontiers in Pediatrics.

“Primary hyperoxaluria type 1 is a rare autosomal recessive disease…[that] results in the overproduction of oxalate which is mostly excreted by the kidneys in the form of calcium oxalate crystals,” authors wrote. “Oxalate deposition causes recurrent nephrolithiasis, nephrocalcinosis, and may eventually damage the tubules, leading progressively to a loss in kidney function and systemic oxalosis.”

The case report involved a patient who was 13 years of age and had received other forms of treatment since age 3, including hyperhydration, potassium citrate, and an average of 5 urological surgeries per year from 2015-2020.

The patient began receiving lumasiran subcutaneous injections at the end of March 2020. Lumasiran is a liver-directed RNA interference (RNAi) therapeutic agent.

Dosage was 3 mg/1 kg of body weight. The first 3 doses were administered once per month and maintenance doses were administered once every 3 months following.

After 1 month of treatment, researchers recorded a “rapid and sustained” reduction in urinary oxalate/creatinine ratio from .25 mol/mol to .08 mol/mol, noting that values <.06 mol/mol are considered normal. This effect remained throughout the 18-month follow-up period.

Treatment also resulted in a decrease of plasma oxalate levels from 32 micromol/L to 13 micromol/L. Normal values are <27 micromol/L.

“Normal plasma oxalate levels were reached immediately after the first dose and the values remained consistently low during the 18 months follow-up period,” authors said.

Treatment with lumasiran resulted in mean reductions in urinary oxalate and plasma oxalate levels of 70% and 60%, respectively.

Researchers also noted that estimated glomerular filtration rate (eGFR) remained stable before and after lumasiran was administered.

“Kidney ultrasonography, which was performed at baseline and at the time of each lumasiran injection, showed no substantial changes,” authors reported. “However, in the 18 months follow-up postlumasiran, no new stones were observed, and the existing ones did not increase in size. The patient did not suffer renal colic events and did not require urgent urological intervention.”

Lumasiran was “very effective” in lowering plasma oxalate and urinary excretion, researchers concluded.

“Though our paper has the main limitation of being a single case report, as far as we know, it covers the longest observation period after initiation of this novel RNAi therapy,” authors said.

Reference:
Chiodini B, Tram N, Adams B, Hennaut E, Lolin K, Ismaili K. Case report: sustained efficacy of lumasiran at 18 months in primary hyperoxaluria type 1. Front Pediatr. Published online January 5, 2022. 2022;9:791616. doi:10.3389/fped.2021.791616