ILLUMINATE-C Phase III open-label study of Oxlumo shows efficacy in primary hyperoxaluria type 1.- Alnylam Pharmaceuticals

Lumasiran resulted in substantial reductions in plasma oxalate (POx) in PH1 patients with chronic kidney disease (CKD) stage 3b-5, with or without dialysis. Elevated plasma oxalate is directly correlated with the pathophysiology of systemic oxalosis, a life-threatening complication of PH1. Lumasiran demonstrated an acceptable safety profile through Month 6, with mild injection site reactions (ISRs) as the most common drug-related adverse event.

ILLUMINATE-C enrolled 21 patients: six patients in Cohort A who did not require dialysis and 15 patients on hemodialysis in Cohort B. The primary efficacy endpoint of the study was the percent change in POx (Cohort A) and predialysis POx (Cohort B) from baseline to Month 6, averaged across Months 3 to 6. Treatment with lumasiran in Cohorts A and B, respectively, led to 33 percent and 42 percent mean reductions in POx and predialysis POx from baseline to Month 6. Reduction in POx was evident by Month 1 and persisted through the end of the 6-month primary analysis period. Lumasiran also demonstrated positive results across secondary endpoints, including patients in Cohort B achieving substantial reductions in POx area under the curve (AUC) 0-24h between dialysis sessions from baseline to Month 6, and lumasiran demonstrating consistent reductions across all measures of urinary oxalate in Cohort A. In addition, a similar magnitude of plasma glycolate increase, an exploratory endpoint in Cohorts A and B, was observed as compared to previously completed studies in patients with relatively preserved kidney function (ILLUMINATE-A and ILLUMINATE-B), suggesting similar pharmacodynamics of lumasiran regardless of kidney function.

Mild and transient ISRs were the most common drug-related AE reported in 24 percent (5/21) of patients. There were no deaths and no serious or severe AEs related to lumasiran. Furthermore, there were no treatment discontinuations or study withdrawals. Results from a separate modeling analysis were also presented at ASN Kidney Week, predicting a long-term reduction in kidney failure risk among PH1 patients treated with lumasiran, assuming prompt treatment at diagnosis. The clinical data were presented at a late-breaking session at the American Society of Nephrology (ASN) Kidney Week being held as a virtual event on November 4-7.