siRNA JNJ-73763989 decreases HBsAg and HDV RNA in NA-treated hepatitis D patients but may cause ALT flares.
J HepatolMay 15, 2026 (epub)
Clinical ResearchGastroenterology
Heiner Wedemeyer, Ed Gane, Kosh Agarwal et al.
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In 30 seconds
The REEF-D study, a phase II randomized controlled trial, evaluated the siRNA JNJ-73763989 in 22 adults with chronic hepatitis D. The treatment led to a ≥2 log 10 IU/ml reduction in HDV RNA in 24% of participants receiving JNJ-3989 compared to none in the deferred group. However, 71% of active-arm participants experienced ALT elevations.
Key findings
- 24% of participants in the active arm achieved a ≥2 log 10 IU/ml reduction in HDV RNA.
- 71% of active-arm participants experienced ALT elevations leading to treatment discontinuation.
- Mean reductions at TW48 were 1.75 log 10 IU/ml for HBsAg and 1.52 log 10 IU/ml for HDV RNA in the active arm.
Why it matters
The findings highlight the potential of JNJ-3989 in reducing viral load in chronic hepatitis D, but also raise concerns about ALT elevations, which are critical for managing patient safety and treatment strategies.