Inside Look: Janssen’s HBV Asset Licensed From Arrowhead Could Become Treatment Franchise Cornerstone

illustration of Hepatitis B in bloodstream

Six months after forging a hepatitis B drug development deal valued at more than $3.7 billion with Arrowhead Pharmaceuticals, Janssen Pharmaceutical presented data that showed its RNA interference (RNAi) therapeutic candidate exhibited robust effects on the liver disease that takes the lives of more than 900,000 people annually.

At the 2019 European Association for the Study of the Liver (EASL) International Liver Congress in Vienna, Austria, Janssen, a division of Johnson & Johnson, and Arrowhead unveiled data from an ongoing Phase I/II clinical study of JNJ-3989. The trial. AROHBV1001 is a double-blind, single dose escalating study in healthy volunteers and open-label, multi-dose escalating study in patients with chronic hepatitis B.

James Merson, Global Therapeutic Area Head for Infectious Diseases at Janssen Research & Development, told BioSpace ahead of the presentation that the data presented at the conference is a key finding. Although the data is still young and faces years of study, Merson said Janssen is highly excited by the findings. He speculated that the data from the study could eventually set the stage for a potential functional cure for HBV, much like HCV has seen with the development of medications like Gilead Science’s Harvoni and Sovaldi.

So far, in the Phase I/II trial, the RNAi product previously known as ARO-HBV targets the hepatitis RNA specifically and stops it making surface antigens, Merson said.

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The ongoing Phase II portion of the trial assesses three subcutaneous doses of JNJ-3989 administered weekly to monthly in HBeAg-positive or negative chronic hepatitis B patients. Study data showed the RNAi therapeutics rapidly reduced hepatitis B surface antigen (HBsAg) in patients that had 24 weeks or more of HBsAg assay results to thresholds possibly associated with improved chances of HBsAg seroclearance in many patients, after only three doses. Additionally, JNJ-3989 reduced all measurable viral products, including HBsAg in hepatitis B e-antigen (HBeAg) positive or HBeAg negative patients.

In the presentation, Arrowhead said duration of pharmacologic effect from the asset persisted for more than four months after last dose. Additionally, the companies noted that JNJ-3989 administered subcutaneously was well tolerated at doses up to 400 mg in all chronic hepatitis B patients.

In the trial, 168 total doses, three doses each, were administered to 56 chronic hepatitis B patients. There were no trial dropouts and Arrowhead, which presented the data at the liver conference, said that there were no drug-related serious adverse events (SAE) reported during the trial.

There are between 270 million and 300 million HBV cases across the globe. It is a difficult disease to treat, Merson said. Likening HBV to HIV, current treatment options do not eliminate the source of the viral infection. If you stop taking medication for HBV, the virus will return and the liver disease will continue to progress, he said.

“We want to increase the functional cure rate,” Merson told BioSpace from Austria. “Hepatitis C has been a big success story but this has been fundamentally challenging.”

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There is hope that the asset Janssen licensed from Arrowhead will be part of the platform on which J&J plants its flag for hepatitis B treatment. During the liver conference, the two companies said JNJ-3989 “exhibits characteristics desirable for a cornerstone therapy in finite regimens aimed at HBsAg seroclearance in patients with chronic hepatitis B infection.”

Janssen and Arrowhead made multiple presentations at the liver conference and the hope is that one or more of these will become weapons against this disease. With the liver conference having come to a close, Merson said Janssen’s next step will be to work out which of the molecules in the pipeline will be able to be combined to “give a high cure.” While he said the company wants to see those high cure rates, it will take work and years of research to determine how high of a cure rate can be achieved. Merson said in its arsenal against HBV, Janssen has multiple assets, which means the company has multiple shots on goal.

“That will be our focus in the coming years,” Merson said.

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