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A decade ago, drug firms were becoming disenchanted with RNA interference (RNAi) technology, which uses small interfering RNA (siRNA) molecules to turn down the expression of disease-causing genes. But the RNAi company Alnylam Pharmaceuticals has launched three commercial siRNA therapies in the past 3 years, and companies are investing in the genetic technology once again.
GlaxoSmithKline has signed an agreement with the RNAi company Arrowhead Pharmaceuticals to develop an siRNA therapy for nonalcoholic steatohepatitis (NASH), a form of fatty liver disease. The therapy, currently in a Phase 1/2 clinical trial, targets a gene, HSD17B13, that encodes an enzyme linked to inflammation in NASH. GSK will pay Arrowhead $120 million initially and up to $910 million in milestone payments.
And Novo Nordisk will acquire the RNAi company Dicerna Pharmaceuticals for $3.3 billion. The two firms began collaborating in 2019 on siRNAs that target more than 30 genes in liver cells as potential therapies for NASH, type 2 diabetes, obesity, and rare diseases. The first clinical trial from that partnership could begin in 2022.
Novo Nordisk will also gain Dicerna’s own pipeline. Dicerna’s most advanced program, currently in a Phase 3 trial, is an siRNA therapy for primary hyperoxaluria, a rare genetic disease in which the overproduction of oxalate in the liver can cause the formation of dangerous crystals in the kidney. Dicerna also has partnerships with multiple drug companies, including Alexion Pharmaceuticals, Alnylam, Boehringer Ingelheim, Eli Lilly and Company, and Roche.
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