Alnylam announces ILLUMINATE-A trial meets primary, secondary endpoints
Alnylam announced that the ILLUMINATE-A Phase 3 study of lumasiran, an investigational RNAi therapeutic targeting glycolate oxidase, or GO, in development for the treatment of primary hyperoxaluria type 1, or PH1, met its primary efficacy endpoint and all tested secondary endpoints. Specifically, lumasiran met the primary efficacy endpoint of percent change from baseline, relative to placebo, in 24-hour urinary oxalate excretion averaged across months three to six. The study also achieved statistically significant results for all six tested secondary endpoints. Lumasiran also demonstrated an encouraging safety and tolerability profile. Based on these results, the company plans to submit a new drug application, or NDA, and file a marketing authorization application, or MAA, for lumasiran in early 2020. ILLUMINATE-A, a randomized, double-blind, placebo-controlled trial, designed to enroll approximately 30 patients with PH1 ages six and above, at 16 study sites, in eight countries around the world, is the largest interventional study conducted specifically in PH1. Patients were randomized 2:1 to lumasiran or placebo, with lumasiran administered at 3 mg/kg monthly for three months followed by quarterly maintenance doses. The primary endpoint for the study was the percent change from baseline in 24-hour urinary oxalate excretion averaged across months three to six in patients treated with lumasiran as compared to placebo. At six months, lumasiran met the primary endpoint in patients with PH1 and achieved statistically significant results for all six hierarchically-tested secondary endpoints, including the proportion of lumasiran patients that achieved near-normalization or normalization of urinary oxalate levels, relative to placebo. There were no serious or severe adverse events in the study, and results showed that lumasiran was generally well tolerated with an overall profile generally consistent with that observed in Phase 1/2 and open-label extension studies of lumasiran. Full ILLUMINATE-A study results will be presented in an oral plenary session on March 31, 2020 at OxalEurope International Congress. The company is also conducting ILLUMINATE-B - a global Phase 3 study of lumasiran in PH1 patients less than six years of age, with results expected in mid-2020, and ILLUMINATE-C - a global Phase 3 study of lumasiran in PH1 patients of all ages with advanced renal disease, with results expected in 2021.