- Arrowhead Pharmaceuticals, a company aiming to make drugs with a technology known as RNA interference, announced Monday that it has licensed out an experimental medicine for a common liver disease to GlaxoSmithKline, in a deal that could potentially be worth more than a billion dollars.
- Called ARO-HSD, the medicine is designed to hinder the body from producing an enzyme involved in the metabolism of hormones, fatty acids and bile acids. ARO-HSD is currently being tested in a small clinical study of patients with NASH, or nonalcoholic steatohepatitis, a disease caused by the buildup of fat in the liver. It's estimated that NASH affects millions of people in the U.S. alone.
- Per deal terms, GSK is handing over $120 million upfront and, possibly, another $130 million if Arrowhead's drug generates positive data in a mid-stage study and then advances to a late-stage trial. Should the drug make it to market, Arrowhead could also receive additional milestone payments worth up to $780 million.
The optimism around drugs for NASH, at a high nearly three years ago, has since crested and crashed, as experimental treatments from Intercept Pharmaceuticals, Gilead, GenFit and Allergan were either delayed or failed in testing. A pipeline that in early 2019 looked set to deliver several new treatments for a disease fast growing in prevalence now appears a much more uncertain prospect.
But drugmakers are still investing. Gilead this year partnered with Novo Nordisk to test whether pairing two of its experimental therapies with the Danish drugmaker's approved medicine Ozempic could help reverse the liver damage that NASH causes. And just last week, Novo said it would buy Dicerna Pharmaceuticals, in part for the biotech's work in NASH.
Arrowhead specializes in the same kind of drugmaking technology that Dicerna does, using strands of nucleic acids to silence the expression of genes. Known as RNA interference, this Nobel Prize-winning science allows drugmakers to shut down the production of disease-causing proteins. Several RNAi drugs from Alnylam Pharmaceuticals are already approved in rare diseases.
Arrowhead, along with its new partner GSK, envision RNAi working for more common diseases like NASH, particularly as the liver is one of the most accessible targets for drugs using the technology. The drug at the center of their deal, ARO-HSD, is designed to reduce levels of an enzyme known as HSD17B13. According to the companies, when mutations in the gene encoding for the enzyme disable it, the risk of alcoholic hepatitis, liver cirrhosis and NASH are reduced.
Earlier this month, Arrowhead presented early data showing its drug nearly eliminated messenger RNA encoding for HSD17B13, which resulted in lower levels of the relevant protein. Half of the 18 NASH patients in the study experienced reductions in liver fat and a third had reduced liver stiffness, Arrowhead said in a Nov. 12 statement.
"The compelling genetic evidence linking HSD17B13 variants with protection of the liver from inflammatory injury suggests that there is an opportunity to produce a first-in-class medicine to reduce the clinical consequences of NASH," said John Lepore, head of research at GSK, in a statement on the companies' partnership Monday.
While GSK is putting up $120 million to license rights, much of the deal's value is back-loaded, with payments for positive trial data and reaching sales milestones should the medicine win approval.
ARO-HSD isn't Arrowhead's only experimental NASH drug. Johnson & Johnson is working with the company on another, which is aimed at a different target in the liver.