Edward Gane of Auckland Clinical Studies in
New Zealand presented findings from a phase 1 study evaluating the safety,
tolerability, pharmacokinetics and anti-HBV activity of RO7049389.
Part 1 of the study, which enrolled 65 healthy
volunteers without HBV, looked at the safety and pharmacokinetics of single
ascending oral doses ranging from 150mg to 2000mg, with and without food, and multiple
ascending doses ranging from 200mg to 600mg twice daily for 14 days. All were
men, about 70% were white, 16% were Asian and the median age was approximately
The second part, enrolling people with
chronic HBV infection, is assessing the drug's antiviral activity at multiple
doses. Gane reported findings from the first cohort of six patients treated
with 200mg RO7049389 twice daily for 28 days plus one placebo recipient. Five
were men, six were Asian, one was white and the median age was 40 years; three
were hepatitis B 'e' antigen (HBeAg) positive, which is more difficult to treat.
They were not currently on HBV treatment, did not have liver cirrhosis or high
ALT elevation and had a viral loads of least 2000 IU/ml if HBeAg negative or
20,000 IU/ml if HBeAg positive.
RO7049389 had a favourable pharmacokinetic
profile, with a half-life of 5.5 hours. Treatment was well tolerated by both
healthy volunteers and people with HBV. Only three people had adverse events that
were considered drug-related (nausea, abdominal upset, skin rash and headache)
and all were mild. There were no clinically meaningful changes in laboratory
All participants with hepatitis B who took
RO7049389 for four weeks experienced "rapid and profound" viral load suppression,
Gane reported. The median HBV DNA decline was -2.7 log10 and the
maximum decline was -3.4 log10. The three HBeAg-negative people,
who started with lower viral levels, became undetectable; viral load was still
declining in the HBeAg-positive participants.
Gane did not report changes in HBsAg or HBeAg levels,
but preclinical studies showed that higher doses of RO7049389 reduced HBsAg and HBeAg in mice.
"These preliminary data support the
further development of RO7049389 as a potential component of a novel
combination HBV cure regimen," the researchers concluded.
Gane said that other cohorts in this ongoing
study will evaluate higher doses and a once-daily dosing schedule.
In a related presentation, Lu Gao and colleagues of the Roche Innovation Centre in Basel reported
findings from a mouse study testing RO7049389 in combination
with the toll-like receptor 7 (TLR7) agonist RO7020531, a drug that activates T
cells, B cells and natural killer cells.
The combination produced sustained HBV DNA
suppression that lasted for six weeks after the drug was stopped in four of the
seven treated mice. It also led to HBsAg loss in five mice and some developed