Lumasiran Meets Primary End Point in Phase 3 Study in Patients With PH1

Drug maker Alnylam Pharmaceuticals has announced that the ILLUMINATE-A trial, a phase 3 study of lumasiran, an investigational RNA interference product targeting glycolate oxidase, met its primary end point in a study of patients with primary hyperoxaluria type 1 (PH1).

The ultrarare disease causes calcium oxalate crystals to form in the kidney and urinary tract and can lead to recurrent kidney stones and nephrocalcinosis.

In the trial, the proposed treatment, which is a subcutaneously administered product that silences hydroxyacid oxidase 1 and depletes the glycolate oxidase enzyme, met its primary end point of percent change from baseline, versus placebo, in 24-hour urinary oxalate excretion averaged across month 3 to month 6.

The drug also revealed what the company called an “encouraging safety and tolerability profile,” and the company reports that there were no serious adverse events in the study period.

“We are very pleased to report positive topline phase 3 results for lumasiran, our third wholly owned investigational RNAi therapeutic,” said Akshay Vaishnaw, MD, PhD, president of research and development at Alnylam.

“Patients living with PH1 and their families are faced with the burden of recurrent and painful stone events and a progressive and unpredictable decline in kidney function that ultimately results in end-stage renal disease and the need for intensive dialysis as a bridge to dual liver/kidney transplantation. The results from ILLUMINATE-A demonstrate that lumasiran can significantly reduce the hepatic production of oxalate, which we believe can thereby address the underlying pathophysiology of PH1,” added Vaishnaw.

The company is also conducting ILLUMINATE-B, a phase 3 study of lumasiran in children aged under 6. Results in that trial are expected by the middle of next year. ILLUMINATE-C will investigate the drug in patients of all ages who have advanced renal disease, and results are expected in 2021.

Alnylam plans to submit a New Drug Application for the product to the FDA in early 2020.