GSK Goes All-In on NASH in $1 Billion Arrowhead Pact

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GlaxoSmithKline has signed an exclusive license deal with Arrowhead Pharmaceuticals to develop and commercialize Arrowhead's investigational RNA interference (RNAi) drug to treat nonalcoholic steatohepatitis (NASH). 

ARO-HSD, the RNAi in focus, will be evaluated in a Phase I/II trial that will assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of its ability to target HSD17B13 as a treatment for NASH. HSD17B13 is part of the hydroxysteroid dehydrogenase family that metabolizes fatty acids, hormones and bile acids. Loss of function mutation in this component has been observed to provide a strong shield against alcoholic cirrhosis, hepatitis and NASH. It has also demonstrated the ability to reduce the risk for the said diseases in non-carriers by 30% to 50%. 

NASH is an advanced type of non-alcoholic fatty liver disease (NAFLD) that's caused by fat buildup in the liver that eventually leads to organ scarring. It is common in patients who are overweight or obese. To date, there is no standard of treatment for NASH but interventions to slow its progression involve drastic lifestyle changes such as losing weight and adopting a healthy diet. Unaddressed NASH that leads to scarring can lead to a deadly condition called cirrhosis.

Under the terms of the deal, GSK will pay $120 million to Arrowhead upfront. The latter will also be eligible for future payments amounting to $30 million when the Phase II trial starts and $100 million upon the successful completion of the Phase II study and when the first patient for Phase III has been dosed. If the Phase III trial delivers positive results, Arrowhead stands to gain as much as $190 million in additional payments at the first commercial sale and then another $590 million maximum in sales-related milestones hit. 

In exchange, GSK will get to exclusively develop and commercialize ARO-HSD in all territories, except Greater China (which remains with Arrowhead). GSK will also be responsible for any further clinical development and commercialization globally. 

"GSK has a global reach and impressive capabilities in the clinical development and commercialization of important medicines. As the work continues towards progressing further Phase 2 studies and planning Phase 3 studies for ARO-HSD, we believe this agreement with GSK furthers the potential of ARO-HSD as a promising new investigational therapeutic for patients with NASH and other liver diseases. We look forward to enabling GSK to advance ARO-HSD towards the millions of patients worldwide who do not have adequate treatment options," said Christopher Anzalone, Ph.D., the president and chief executive officer of Arrowhead, in a statement. 

As of this writing, ARO-HSD is being investigated in a Phase I/II single and multiple-dose escalating trial involving 74 normal healthy volunteers and patients diagnosed with NASH or suspected to have NASH. Other exploratory objectives of the test include the use of liver biopsy to assess different measures of drug activity. 

The transaction has yet to receive clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 but is expected to close by the first quarter of 2022.

Earlier this month, Arrowhead announced that it is entering a Phase I clinical study with Janssen Pharmaceuticals to explore a siRNA therapeutic called JNJ-75220795 also as a potential treatment for NASH. Under this arrangement, Janssen will use Arrowhead's TRIM platform.

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