Phase 2 trial of JNJ-73763989-based regimen shows no HBsAg seroclearance at primary endpoint in HBeAg-positive CHB
This phase 2, single-arm trial enrolled 54 treatment-naïve, HBeAg-positive chronic hepatitis B patients. The intervention was a 36- to 52-week induction with JNJ-73763989 (200 mg every 4 weeks) plus nucleos(t)ide analogues, with or without bersacapavir (250 mg daily), followed by 12 weeks of add-on peginterferon alfa-2a (180 µg weekly). No comparator group was reported.
The primary endpoint was HBsAg seroclearance 24 weeks after stopping all treatment, which was achieved by 0 of 54 participants. However, 11 participants (20.4%) achieved HBsAg seroclearance at least once during the study, with 6 maintaining it until the 48-week follow-up. Mean HBsAg levels decreased substantially: by -2.85 logIU/mL at the end of induction, -3.61 logIU/mL at end of treatment, and -2.63 logIU/mL at follow-up. HBeAg seroclearance was achieved at least once by 16 of 53 participants (30.2%), with 12 maintaining it.
Adverse events were common, reported in 83.3% of participants during induction and 85.7% during the peginterferon alfa-2a phase. Key limitations include the small sample size, lack of a control arm, and the preliminary nature of the abstract data, which lacks statistical comparisons and full safety details. The regimen's complexity and high AE rate warrant caution.
For practice, this early-phase study shows a novel combination can induce significant HBsAg declines and transient seroclearance in some patients, but it failed its primary endpoint. The findings are hypothesis-generating for future combination strategies but do not support a change in current management.
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