Arrowhead RNAi drug clears hepatitis B antigen in clinic

hepatitis B virus
The hepatitis B virus (University of Wisconsin–Madison)

Arrowhead Pharmaceuticals’ RNAi therapy ARC-520 has cleared the hepatitis B surface antigen from a patient in a small study. The seroclearance gives a boost to Arrowhead as it plots a path back from safety concerns that derailed ARC-520 in 2016.

Pasadena, California-based Arrowhead designed ARC-520 to turn the body’s RNAi machinery on hepatitis B RNA transcripts, thereby reducing levels of viral proteins and RNA and enabling the immune system to mount more effective attacks. Arrowhead shelved the candidate following deaths in nonhuman primates. But, with ARC-520’s successor now in the clinic, Arrowhead has posted data suggesting the RNAi approach has promise on the efficacy front.

The data come from an eight-person extension to an earlier ARC-520 study. Having received a single intravenous dose in the original trial, the participants received up to nine more hits in the extension.    


Share your opinion. Take our five minute survey.

How do you select the most suitable advanced dosage forms for new molecules in your development pipelines? Share your insights in this 5-minute survey. The first 50 qualified respondents will receive a $5 Amazon gift card.

For one patient, the regimen was strong enough to clear out the hepatitis B surface antigen HBsAg. The level of the antigen in the patient fell quickly following treatment with ARC-520 and the antiviral entecavir. Other drugs can trigger seroclearance but there is scope to improve on the therapies. The experience of serocleared patients shows the status is associated with good long-term outcomes. 

RELATED: Arrowhead snaps after trial hold as it targets major layoffs, ditches programs

Other participants in the extension experienced declines in HBsAg levels. 

Arrowhead’s decision to drop ARC-520 means the data are irrelevant for that asset. But they provide a source of confidence in the RNAi-based approach to treating hepatitis B that lives on in ARO-HBV. Arrowhead began dosing participants in a 60-patient phase 1/2 trial of the candidate last month.   

The follow-up candidate works in a similar way to ARC-520, muting hepatitis B genes to give the immune system a chance to rally. It is early days for ARO-HBV—the trial is due to wrap up in around a year—but the data shared this week suggest the rationale is sound.   

Shares in Arrowhead ticked up 6% in premarket trading.

Suggested Articles

The FDA rejected the new drug application for golodirsen, the follow-up to Exondys 51, Sarepta’s first treatment for Duchenne muscular dystrophy.

Levi Garraway is set to take up one of the biggest hot seats in biopharma when he becomes the next chief medical officer at Roche.

The FDA approved a new device for people suffering from advanced heart failure who are not able to receive treatment from other devices.