Alnylam makes case for lumasiran in infants ahead of FDA ruling  

John Maraganore casual
Alnylam CEO John Maraganore (Alnylam)

Alnylam has shared data from a phase 3 trial of its near-approval kidney disease drug lumasiran in children as young as three months. The RNAi therapy drove a 72% reduction in urinary oxalate from baseline, boosting Alnylam’s hopes of using the drug in a broad patient population.

Earlier this year, Alnylam filed for FDA approval of lumasiran on the strength of data linking it to a 65% drop in urinary oxalate in people with primary hyperoxaluria type 1 (PH1) aged six years and up. Last month, Alnylam followed up with news that lumasiran drove a “clinically significant” decline in urinary oxalate in children aged three to 72 months but held off on publishing the data.

Alnylam used American Society of Nephrology Kidney Week 2020 to share results from the phase 3 trial. Investigators tracked a 72% mean reduction in urinary oxalate across the 18 subjects over the first six months of the study, suggesting lumasiran works in both younger and older children.

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The secondary endpoints bolster Alnylam’s case. Half of the patients had urinary oxalate levels at or below 1.5 times the upper limit of normal. The data on urinary oxalate, a key driver of negative outcomes in PH1 patients, suggest lumasiran is working as intended. Lumasiran is designed to target the gene encoding for glycolate oxidase and, in doing so, reduce the production of oxalate.

Alnylam is building the case for the effect of lumasiran on other outcomes. Eight of the subjects had unilateral or bilateral improvements in nephrocalcinosis, a kidney disorder driven by the depositing of calcium. The other 10 subjects were stable.  

There was no change in renal stone events, potentially due to the relatively short duration of the trial. Alnylam has more data from the phase 3 trial that enrolled people aged six years and up. With 12-month results now available, Alnylam has linked reductions on oxalate levels to lower rates of renal stone events.

The 12-month update also provided evidence of the continued efficacy of lumasiran. The reduction in urinary oxalate from baseline held steady over the second six months of the study. 

Neither trial has seen a death, serious adverse event, discontinuation of treatment or withdrawal related to the study drug. Mild, transient injection site reactions were the most common drug-related adverse event, but only three of the 18 subjects in the study of infants had such responses. 

Alnylam is preparing to use the data to support the launch of lumasiran on both sides of the Atlantic under the brand name Oxlumo. The Committee for Medicinal Products for Human Use gave a positive opinion last week, putting Alnylam on the cusp of winning approval in Europe, and the FDA is set to make a decision by early December. 

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