25 Oct, 2018 New Clinical Results from Phase 1/2 and Phase 2 OLE Studies of Lumasiran at ASN 2018 Annual Meeting
We presented new results from the Phase 1/2 and Phase 2 open-label extension (OLE) studies of lumasiran at the American Society of Nephrology (ASN) 2018 Annual Meeting, held October 23-28, 2018 in San Diego, CA.
Plasma oxalate data (N=10)* from the Phase 1/2 study were as of a data cut-off of August 15 and demonstrated a 75 percent mean maximal reduction (range: 57-94 percent) relative to baseline. Fifty percent of patients achieved plasma oxalate levels within the normal range (less than 1.6 µmol/L). Reductions in plasma oxalate paralleled sustained reductions in urinary oxalate, which were previously reported at the 2018 European Society of Paediatric Nephrology (ESPN) Annual Meeting; safety results for the Phase 1/2 study were also as reported at ESPN.
For those patients who have transitioned to the Phase 2 OLE study, which is designed to evaluate long-term safety and efficacy, the tolerability profile of lumasiran remains generally consistent with data from the Phase 1/2 study. Phase 2 OLE safety results (N=8) were based on a median study duration of 2.7 months (range: 0.03 to 3.02 months) since first dose. As of the data cut-off date of October 3, there were no discontinuations from study treatment. Serious adverse events (SAEs) were reported for two patients (25 percent), one with traumatic brain injury and contusion – sustained in a car accident – and one with nephrolithiasis**; none were assessed as related to study drug. Adverse events (AEs) were reported in five patients (63 percent); all were mild or moderate in severity and majority were assessed as unrelated to study drug. There were no reports of injection site reactions or clinically significant laboratory changes and increased glycolate levels were not associated with any safety findings.
We continue to be encouraged by the totality of data across the lumasiran program, and look forward to building upon that with the ongoing ILLUMINATE-A Phase 3 study. Further underscoring the maturation of this program, we are pleased to have expanded Alnylam Act® to cover PH1, and to have aligned with the FDA on a trial design for ILLUMINATE-B, a Phase 3 study of lumasiran in eight PH1 patients under six years of age with relatively preserved renal function.
*Number of patients with samples available for plasma oxalate assessment.
**SAE of nephrolithiasis occurred prior to patient receiving first dose of lumasiran in Phase 2 OLE study.