Johnson & Johnson has presented clinical trial data linking short-term treatment with RNAi therapy JNJ-3989 to sustained reductions in markers of hepatitis B infection. The data drop comes as J&J runs 48-week phase 2b trials of the Arrowhead-partnered drug in the pursuit of a functional cure.
Investigators administered three doses of JNJ-3989 to participants in 56 days to evaluate whether giving the RNAi therapy in combination with an existing treatment can degrade viral RNA and inhibit DNA formation to reduce levels of HBsAg, the surface antigen of the hepatitis B virus. The study then tracked the subjects for 48 weeks after the administration of the final dose of JNJ-3989.
By the end of the follow-up, 15 of the 38 patients who initially responded to JNJ-3989 still had a -1.0 log10 IU/mL or greater reduction in HBsAg. The average 392-day reduction in HBsAg among the 15 sustained responders was around -2.0 log10 IU/mL.
The HBsAg levels of some of the sustained responders were close to J&J’s -1.0 log10 IU/mL cutoff and trending up at the end of the follow-up. That suggests the percentage of participants classed by J&J as sustained responders could fall if their HBsAg levels are assessed again in the future.
J&J also looked at the effect of JNJ-3989 on levels of hepatitis B RNA and two other viral antigens. The analyses followed the same broad pattern as the HBsAg assessment, with the levels in some subjects rebounding in the weeks and months after the last dose while staying suppressed in some of their peers.
No new drug-related adverse events were seen from day 85 to day 392. One abnormal liver function test was reported. No additional grade 3 or 4 laboratory abnormalities during the treatment phase were reported.
J&J’s researchers hailed the clinical data as the first time a “siRNA therapy resulted in sustained, off-treatment >=1log10 IU/mL reductions in HBsAg through to 48 weeks” after the last dose. The goal now is to show such sustained reductions in a larger group of patients than the 40-subject cohort evaluated in the phase 2 trial.
The ongoing phase 2b trials will provide a clearer picture of whether J&J can deliver on its ambition to develop a functional cure and establish JNJ-3989 as a competitor in a market being targeted by rivals including Roche and Vir Biotechnology. J&J, Vir and Roche, through its partnership with Dicerna Pharmaceuticals, have shown their assets deliver similar short-term reductions in HBsAg in relatively small trials. The focus now is on delivering lasting reductions in larger clinical trials.
J&J and its rivals are committing sizable sums to their pursuit of the hepatitis B opportunity. Roche paid Dicerna $200 million to secure the global license to RG6346, while J&J handed Arrowhead $250 million to pick up JNJ-3989.