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.
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.
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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.