RO7049389 is safe, well tolerated in chronic hepatitis B treatment
Core protein allosteric modulator RO7049389 was safe and demonstrated antiviral activity in patients with chronic hepatitis B infection, according to research published in Lancet Gastroenterology and Hepatology.
“Current treatment options for patients with chronic HBV infection comprise two classes of drugs: subcutaneously administered interferon preparations and orally administered nucleotide analogues. Neither treatment achieves a high rate of functional cure, defined as sustained loss of hepatitis B surface antigen with or without seroconversion to [hepatitis B surface] antibody (anti-HBs) positivity,” Man-Fung Yuen, MD, PhD, of the University of Hong Kong, and colleagues wrote. “Thus, there is a huge unmet medical need for well-tolerated therapies for chronic HBV infection that can achieve a higher rate of functional cure with a finite course of treatment.”
In a multicenter, randomized, placebo-controlled phase 1 study, researchers investigated the safety, pharmacokinetics and antiviral activity of RO7049389 in 37 patients with HBV (62% men) aged 18 to 60 years. A previous study confirmed its safety and tolerability among healthy study participants. Investigators randomly assigned patients to receive RO7049389 dosed at 200 mg twice daily, 400 mg twice daily, 200 mg once daily, 600 mg once daily, 1,000 mg once daily or placebo for 4 weeks. Following final dosage, post-treatment follow-up took place at 12 weeks. Researchers noted a mean HBV DNA concentration of 5.9 log10 IU/mL at baseline across all treatment groups.
The data showed mean HBV DNA concentration declines from baseline of 2.44 log10 IU/mL in the 200 mg twice daily group, 3.33 log10 UI/mL in the 400 mg twice daily group, 3 log10 IU/mL in the 200 mg once daily group, 2.86 log10 IU/mL in the 600 mg once daily group and 3.19 log10 IU/mL in the 1,000 mg once daily group Mean HBV DNA concentration decline was 0.34 log10 IU/mL in the placebo group.
The most common adverse events included headache (16%), increased alanine aminotransferase level (16%), increased aspartate aminotransferase level (13%), upper respiratory tract infection (13%) and diarrhea (10%); all adverse events were of mild or moderate intensity.
“In conclusion, 28 days of RO7049389 treatment up to a daily dose of 1,000 mg was safe and well tolerated, and demonstrated substantial HBV DNA and HBV RNA declines in both HBeAg-positive and HBeAg-negative patients,” Yuen and colleagues added. “These results provide proof of mechanism for further clinical development of RO7049389 as a component of novel combination anti-HBV regimens for patients with chronic HBV infection.”