Alnylam Presents Positive Results from ILLUMINATE-B Phase 3 Study in Pediatric Patients with Primary Hyperoxaluria Type 1 at the American Society of Nephrology Kidney Week - Seite 2

ILLUMINATE-B 6-Month Results

Alnylam presented positive efficacy and safety results from the 6-month primary analysis (N=18) of the ILLUMINATE-B Phase 3 study of lumasiran in infants and children under the age of 6, with the youngest patient enrolled at 3 months of age. The efficacy results and safety profile of lumasiran were found to be similar to those observed in adults and children 6 years or older in the ILLUMINATE-A study. Treatment with lumasiran in ILLUMINATE-B led to a 72 percent mean reduction in spot urinary oxalate:creatinine ratio from baseline to Month 6, averaged across months 3 to 6 – the primary endpoint of the study. Lumasiran also demonstrated positive results across secondary endpoints, including proportion of patients (9/18 or 50 percent) achieving urinary oxalate levels at or below 1.5 times ULN^a.

Preliminary analysis of exploratory endpoints indicated improvements in nephrocalcinosis in 8 out of 18 patients (44 percent), while estimated glomerular filtration rates (eGFR) remained stable. At baseline, 14 of 18 patients had nephrocalcinosis. After 6 months of lumasiran treatment, no patients worsened, 10 remained stable, and eight showed bilateral (3 out of 8) or unilateral (5 out of 8) improvements in nephrocalcinosis. As expected, given the 6-month duration of the study, there was no change in the rate of renal stone events (RSEs)^b .

Lumasiran had an acceptable safety profile in infants and young children under the age of six. There were no deaths, severe adverse events, discontinuations of treatment or withdrawals from the study. One patient had a serious adverse event (SAE) of viral infection that was considered not related to lumasiran by the study investigator. The most common drug-related adverse events (AEs) were mild and transient injection site reactions (ISRs) reported in 3 of 18 (17 percent) patients. No clinically relevant changes in laboratory measures (including liver function tests), vital signs, or electrocardiograms related to lumasiran were observed.

ILLUMINATE-A 12-Month Results

As of the data cut-off date of May 1, 2020, results from the extension period of the ILLUMINATE-A Phase 3 study showed that patients initially randomized to lumasiran in the 6-month double-blind (DB) period who continued treatment with lumasiran through Month 12 (“lumasiran/lumasiran”; N=24) maintained their reduction in 24-hour urinary oxalate excretion, with a 64 percent mean reduction relative to baseline. The majority (88 percent) of patients in this group reached normal or near-normal levels (at or below 1.5x ULN)^a of urinary oxalate. In patients who were originally randomized to placebo in the DB period but crossed over to lumasiran (“placebo/lumasiran”; N=13), treatment with lumasiran led to a 57 percent mean reduction in 24-hour urinary oxalate excretion after six months of treatment; 77 percent of these patients reached urinary oxalate levels at or below 1.5 x ULN.