Alnylam reports updated ‘positive’ results from Phase 1/2 study of lumasiran

Alnylam Pharmaceuticals announced updated positive results from its Phase 1/2 clinical study of lumasiran, an investigational, subcutaneously administered RNAi therapeutic targeting glycolate oxidase for the treatment of primary hyperoxaluria type 1. The company also announced the initiation of ILLUMINATE-A, a global Phase 3 pivotal trial of lumasiran in children and adults with PH1. The study will enroll approximately 30 patients and is designed in alignment with FDA with a primary endpoint based on reduction of urinary oxalate at six months. Alnylam expects to report topline results from ILLUMINATE-A in late 2019 and, if positive, submit filings for regulatory approval starting in early 2020. New results from the Phase 1/2 study were as of a data cut-off date of August 15, 2018. Lumasiran demonstrated a mean maximal reduction in urinary oxalate of 75 percent relative to baseline across cohorts dosed at 1 mg/kg monthly or 3 mg/kg monthly or quarterly. The mean reduction relative to baseline was 66 percent when measured 28 days post last dose. All patients achieved oxalate lowering to less than 1.5 times the upper limit of normal. Among patients receiving 3 mg/kg monthly or quarterly doses of lumasiran, 83 percent achieved urinary oxalate levels within the normal range. Furthermore, lumasiran-treated patients in all cohorts experienced a mean maximal decrease of 76 percent in the ratio of urinary oxalate to creatinine – a corroborative measure of oxalate reduction that addresses the variability that is inherent to 24 hour urine collections. The Phase 1/2 safety results in patients with PH1 were based on a median study duration of seven months since first dose. As of the data cut-off date, there were no discontinuations from study treatment. Serious adverse events were reported for one patient receiving placebo and five patients receiving lumasiran; none were related to study drug. The placebo patient experienced acute pyelonephritis and kidney stones. The lumasiran patients with SAEs included one patient with vomiting, one patient with abdominal pain, fever and vomiting, one patient with gastroenteritis, and two patients with kidney stones. Adverse events were reported in three patients during placebo dosing and 19 patients after lumasiran dosing. The majority of AEs were mild or moderate in severity and were assessed as unrelated to study drug. Injection site reactions were reported in three patients receiving lumasiran. ISRs were mild or moderate in severity and were self-limiting. Lumasiran was not associated with any clinically significant adverse laboratory findings. In patients receiving lumasiran, plasma glycolate levels increased consistent with the pharmacology of lumasiran and results from healthy volunteers in Part A of the Phase 1/2 study. This increase was not associated with any safety findings.

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