Positive data reported on Alnylam’s investigational RNAi therapeutic for ultra-rare disease

pharmafile | July 30, 2021 | News story | Medical Communications  

Alnylam Pharmaceuticals has announced that its investigational RNAi therapeutic, lumasiran, has performed well in a Phase III study for the treatment of an ultra-rare disease, advanced primary hyperoxaluria type 1 (PH1).

PH1 affects an estimated one to three individuals per million in the United States and Europe and is characterised by oxalate overproduction in the liver. The excess oxalate results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis.

Lumasiran is targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – and is being investigated for the treatment of adult and paediatric patients with advanced PH1.

Topline results from the ILLUMINATE-C study show that at six months and relative to baseline, treatment with lumasiran resulted in a substantial reduction in plasma oxalate in patients with advanced disease, including those on haemodialysis.

Elevated plasma oxalate is directly related to the pathophysiology of oxalosis and results in systemic deposition of oxalate in extra-renal tissues, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers, and other serious manifestations.

Jeroen Valkenburg, General Manager of the lumasiran programme at Alnylam, said: “People with advanced PH1 suffer from severely impaired kidney function and may require an intensive dialysis regimen as a bridge to receiving a combined liver/kidney transplant – a procedure associated with high morbidity and lifelong immunosuppression.

“In ILLUMINATE-C, lumasiran reduced elevated levels of plasma oxalate that can lead to the morbidity and mortality associated with systemic oxalosis in this particularly vulnerable patient population.”

ILLUMINATE-C was a single arm, open-label, multinational study evaluating the safety and efficacy of lumasiran in PH1 patients of all ages with severe renal impairment, conducted at 13 sites across 10 countries.

Based on the trial results, the Alnylam plans to submit a Supplemental New Drug Application (sNDA) for lumasiran with the U.S. Food and Drug Administration (FDA) and a Type II Variation with the European Medicines Agency (EMA) in late 2021. In November 2020, lumasiran was approved by the FDA for the treatment of PH1 to lower urinary oxalate levels in paediatric and adult patients and by the EMA for the treatment of PH1 in all age groups.

Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation, said: “Patients with PH1 face devastating health challenges, especially those approaching or experiencing kidney failure, and these new results from the ILLUMINATE clinical development programme signal hope to some of the sickest and most severely impacted individuals in this patient community.”

Kat Jenkins

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