Letter to the editor: Is the HBsAg response to RO7062931 an antisense effect?

Gane et al(1) suggest that HBsAg responses in chronic HBV infection to RO7062931, a GalNAc-conjugated antisense oligonucleotide (GalNAc-ASO) indicate target engagement (cleavage of HBV mRNA). The highly conserved target engagement with GalNAc-ASOs is well known from studies with numerous liver targets in humans. Exemplary studies (2, 3) illustrate a rapid and uniform ~1 log10 protein reduction within 15 days in all subjects, occuring with only a single dose and saturating with weekly to monthly dosing from 60mg (0.9 mg/kg) to 90mg (1.4 mg/kg). Given the rapid turnover of HBsAg (4, 5), target engagement with RO7062931 should be accompanied by similar HBsAg responses.