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Arrowhead and Glaxo Pen Down a $1B Pact for RNAi

With a $1 billion asset deal with Arrowhead Pharmaceuticals, GlaxoSmithKline is making its first big step into treating nonalcoholic steatohepatitis (NASH), a fatty liver disease. Arrowhead experimental early clinical-stage RNAi medicine ARO-HSD targets HSD17B13, a member of the hydroxysteroid dehydrogenase family involved in the hormone, fatty acid, and bile acid metabolism with a focus on NASH.

The disease produces a buildup of fat in the liver, which can eventually lead to scarring. It affects millions of people in the United States alone, mainly affecting obese patients or those with Type 2 diabetes.Christopher Anzalone, Ph.D., Arrowhead president, and CEO, told Fierce Biotech ahead of the purchase that he believes one of the reasons others have failed in this market is a concentration on reducing liver fat at the expense of preventing fibrosis.

Many past attempts to address the fat side of the equation in the liver have failed, and ARO-HSD offers a novel strategy to address the fibrosis side of the equation potentially. According to the genetic data, ARO-HSD may also have the potential to treat a variety of other fibrotic liver illnesses.Using RNAi is a relatively novel strategy, but it’s one that Alnylam—the RNAi leader and a former close competitor of Arrowhead—and partner Regeneron are testing in phase 1 trials with their candidate ALN-HSD. NASH, on the other hand, is a high-risk venture:

it has the potential to yield blockbuster sales for the business that gets it right, but poor efficacy, particularly in monotherapies and safety concerns, have impeded and delayed several NASH initiatives in recent years. With such a significant investment, however substantially backloaded, GSK will be hoping for better results, as well as a better outcome than the cancer deal it struck with Merck in Germany.

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