Lumasiran RNAi PH1 Approval — ESENeph MCQ

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HardTubular DisordersLumasiran RNAi PH1 ApprovalESENeph

A 30-year-old woman with primary hyperoxaluria type 1 (PH1) confirmed by AGXT gene mutation has eGFR 55 mL/min/1.73m2 and recurrent calcium oxalate stones despite high fluid intake and pyridoxine. What targeted therapy has been approved for PH1?

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Correct answer: E — Lumasiran

Lumasiran is an RNA interference (RNAi) therapeutic that targets hepatic glycolate oxidase (HAO1) mRNA, reducing substrate availability for oxalate production. It was approved for PH1 based on the ILLUMINATE-A trial, demonstrating dramatic reduction in urinary oxalate excretion (~65% reduction). PH1 is caused by deficiency of alanine-glyoxylate aminotransferase (AGT, encoded by AGXT) in hepatic peroxisomes, leading to glyoxylate accumulation and conversion to oxalate. Lumasiran is administered subcutaneously monthly (loading) then quarterly. Pyridoxine (vitamin B6) is a cofactor for AGT and benefits ~30% of PH1 patients with responsive mutations. Tiopronin is for cystinuria.

Reference: Garrelfs et al 2021 – ILLUMINATE-A Trial; NICE HST18 – Lumasiran for PH1