Alnylam Completes Enrollment for ILLUMINATE-A Phase 3 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 (PH1)
− On Track to Report ILLUMINATE-A Topline Results in Late 2019 –
− In Addition, Company Reports Final Positive Results from Phase 1/2 Study of Lumasiran –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 17, 2019-- Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading RNAi therapeutics company, announced today that it has achieved full patient enrollment in its ILLUMINATE-A Phase 3 study of lumasiran, an investigational RNAi therapeutic targeting glycolate oxidase for the treatment of adults and children with primary hyperoxaluria type 1 (PH1). The study enrolled patients across 16 sites in eight countries. Alnylam is on track to report topline results from ILLUMINATE-A expected in late 2019 and, if positive, to submit filings for global regulatory approvals starting in early 2020. The Company also announced complete positive results from its Phase 1/2 clinical study and reiterated positive results from its ongoing Phase 2 open-label extension (OLE) study of lumasiran. Results will be presented at the 2019 Oxalosis & Hyperoxaluria (OHF) International Workshop being held in Boston, on June 21-22.
“We are pleased to have reached two important milestones for our PH1 program, timely completion of enrollment in ILLUMINATE-A – our Phase 3 pivotal study in adults and children – and successful completion of our Phase 1/2 study with positive final results,” said Pritesh J. Gandhi, PharmD, Vice President and General Manager, Lumasiran program at Alnylam. “We look forward to reporting topline results from the ILLUMINATE-A study expected in late 2019 and believe that lumasiran has the potential to provide a clinically meaningful treatment option for patients living with PH1.”
“With positive Phase 1/2 results where oxalate reduction was observed for every patient and with ongoing ILLUMINATE Phase 3 trials, we are hopeful for the future of our PH1 patient community who have limited options available to them,” said Kim Hollander, Executive Director,Oxalosis & Hyperoxaluria Foundation. “We look forward to continuing to work with Alnylam as they advance lumasiran through multiple Phase 3 studies designed to address the full spectrum of patients affected by PH1.”
In final Phase 1/2 study results, lumasiran demonstrated a mean maximal reduction in urinary oxalate of 75 percent (range: 43-92 percent) relative to baseline across all cohorts (1 mg/kg monthly, 3 mg/kg monthly, and 3 mg/kg quarterly; N=20). At 28 days post the last dose, the mean reduction relative to baseline was 66 percent. All patients (100 percent) achieved oxalate lowering to less than 1.5 times upper limit of normal (less than or equal to 0.69 mmol/24hr/1.73m2). Among patients receiving 3 mg/kg monthly or quarterly doses of lumasiran (N=12), 92 percent achieved urinary oxalate levels within the normal range (less than 0.46 mmol/24hr/1.73m2). Furthermore, lumasiran-treated patients across all cohorts (N=20) experienced a mean maximal decrease of 77 percent (range: 50-95 percent) in the ratio of urinary oxalate to creatinine – an additional measure of oxalate reduction that addresses the variability that is inherent in 24-hour urine collections.
Lumasiran results showed an acceptable safety and tolerability profile, with PH1 patients on study for a median of 9.8 months (range: 5.6 to 15.2 months); there were no study discontinuations. Serious adverse events (SAEs) were reported for one patient (33 percent) receiving placebo and four patients (20 percent) 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 one patient with kidney stones. Adverse events (AEs) were reported in two (66.7 percent) patients during placebo dosing and 20 (100 percent) patients after lumasiran dosing. The majority of AEs were mild or moderate in severity and were assessed as unrelated to study drug. Severe AEs were reported in one (33 percent) patient during placebo dosing (acute pyelonephritis) and one (5 percent) patient after lumasiran dosing (kidney stone); none were considered related to study drug by investigator. AEs reported in more than three patients receiving lumasiran were pyrexia (N=6); vomiting, cough, abdominal pain, headache (N=5 each); and rhinitis and nephrolithiasis (N=4 each). Self-limiting injection site reactions (ISRs) were reported in three (15 percent) patients receiving lumasiran; all mild or moderate and with none affecting dosing. Lumasiran was not associated with any clinically significant adverse laboratory findings, including liver function tests.
As previously reported, all patients (100 percent) who completed Phase 1/2 (N=20) continue dosing in the ongoing Phase 2 OLE phase of the study. As of February 2019, patients in the Phase 2 OLE study have received lumasiran for a median of four months (range: 0.03–8.36; N=18). Lumasiran dosing across all evaluable cohorts (N=9) resulted in mean maximal reduction in urinary oxalate of 72 percent (range: 41-90 percent) relative to Phase 1/2 baseline levels. Multiple doses of lumasiran demonstrated an acceptable safety and tolerability profile in patients with PH1, with no drug related SAEs and no discontinuations from study treatment.
The Company also recently presented a case study of a healthy human with mutations in the HAO1 gene, a validated target for the treatment of PH1, as well as results from research on the diagnostic journey of PH1 at the 56th Congress of the European Renal Association (ERA) and European Dialysis and Transplant Association (EDTA) held on June 13-16, 2019 in Budapest, Hungary. To view the results presented by Alnylam at the ERA-EDTA Congress, please visit www.alnylam.com/capella.