#5036 the outcome of lumasiran treatment in 10 paediatric patients with primary hyperoxaluria type 1

Abstract Background and Aims In primary hyperoxaluria type 1 (PH 1) a rare enzymatic defect in the liver leads to a hepatic overproduction of oxalate. The resulting hyperoxaluria can cause nephrocalcinosis, urolithiasis and renal failure. Conservative treatment options such as hyperhydration, citrate and pyridoxine aim to slow the progression of the disease with a liver transplant currently being the only curative treatment. Since November 2020 Lumasiran is approved for use in patients with PH 1. Lumasiran reduces the hepatic oxalate production by RNA interference and may hence reduce hyperoxaluria. To date there is limited real world data available on the effectiveness of the treatment with Lumasiran. Method This observational study looked at the outcome of Lumasiran treatment in 10 patients under the age of 18 years with genetically confirmed PH 1. The primary end point was percentage reduction in plasma oxalate in the two patients on haemodialysis and percentage reduction of urinary oxalate excretion in the patients with preserved renal function. Secondary end points were change in nephrocalcinosis, urolithiasis and renal function. The follow up time was 6 months in one patient and 12 months in the other nine patients. Results Four of the patients were girls and the median age at the start of treatment was 5.25 years (range 0.3-17.9 years). One of the two patients on haemodialysis showed a decrease in plasma oxalate which allowed for a reduction of dialysis frequency from 5x/week to 3x/week whilst the other patient's dialysis had to be intensified due to worsening systemic oxalosis. In the patients with preserved renal function the median reduction of urinary oxalate was 71% (range 10–91%) after 6 months and 78% (range 61–86%) after 12 months. Two patients reached values in the age specific normal range (Matos et al.). Lumasiran was discontinued after 4 months in one patient and after 8 months in another one due to treatment failure. An improvement in nephrocalcinosis was seen in three patients and two patients showed a subjective reduction in urolithiasis. Renal function improved slightly in one patient and remained stable in the others. Injection site reactions were the only observed side effects. Conclusion Our data highlights the heterogeneity of the disease and treatment response to Lumasiran. Despite promising data regarding the benefits of Lumasiran 2 of 10 patients did not benefit from Lumasiran injections. Hence, it is imperative to regularly re-evaluate hyperoxaluria during treatment with Lumasiran. Ideally the data should be entered into a registry for PH 1 patients to monitor the effectiveness and side effects of this novel drug not only in the short- but also the long term.