Alnylam Pharmaceuticals has just announced that they will be starting a Phase 2 trial for their RNAi therapeutic called Lumasiran. This trial will investigate both the safety as well as the efficacy of the therapy for recurrent kidney stone disease.
Lumasiran targets the hydroxyacid oxidase 1 (HAO1) gene which encodes glycolate oxidase. It has already been FDA approved as a treatment for pediatric patients and adult patients with primary hyperoxaluria type 1 (PH1) as it lowers urinary oxalate levels. Additionally, it’s been approved by the EMA for PH1.
Recurrent Kidney Stone Disease
Kidney stones themselves aren’t uncommon. About 1 out of every 11 people will face one at some point. 80% of these cases are caused by a buildup of calcium oxalate crystals. Kidney stones can cause UTIs, flank pain, painful urination, and blood within the urine. They can require surgery.
Some patients face recurrent calcium oxalate stone disease and elevated levels of urinary oxalate. Recurrent kidney stones can lead to a higher risk of chronic kidney disease (CKD), and ultimately end stage kidney disease (ESKD).
Recurrent kidney stone disease has limited treatment options and even when patients do everything they’re supposed to (diet changes, thiazide diuretics, citrate supplementation, lifestyle changes, etc.), sometimes kidney stones still occur. It is clear a new treatment option is needed.
Since most kidney stones are caused by high oxalate production, reducing urinary oxalate by silencing HAO1 could lead to reductions in stones.
Lumasiran targets HAO1 and inhibits the production of oxalate. As a result, researchers think it may prevent recurrent kidney stone disease.
Phase 2 Study
Lumasiran will be studied in a global Phase 2 trial which is double-blind and placebo-controlled. Researchers will study the safety, efficacy, pharmacodynamics, and pharmacokinetics of the treatment.
The trial will include 120 adult patients who have experienced at least two kidney stones within the last five years and who have high urinary oxalate levels.
Lumasiran will be administered subcutaneously at 284mg or 567mg. The treatment will be administered on day 1, on the 3rd month, on the 9th month, and on the 15th month. There will be a 6 month initial analysis and then a 9 month treatment extension.
The primary endpoint that will be studied is the percentage change in 24 hour urinary oxalate following 6 months of the therapy. The researchers will also evaluate the percentage of participants who reach a 20% or higher reduction. Additionally, they will measure the change in urinary calcium oxalate supersaturation at the 6 month mark.
You can read more about this investigative treatment and the upcoming Phase 2 study here.
