Significant Hepatitis B Virus RNA Declines With ABI-H0731 Plus Nucleos(t)ide Inhibitor: Presented at EASL

By Walter Alexander

VIENNA, Austria -- April 17, 2019 -- In patients with chronic hepatitis B, the combination of ABI-H0731, an investigational core protein inhibitor, plus a nucleos(t)ide inhibitor (Nuc) demonstrates superior antiviral activity versus Nuc alone, according to a study presented here at The International Liver Meeting, the 54th Annual Meeting of the European Association for the Study of the Liver (EASL).

The 2 clinical trials included treatment-naive (study 202) and virologically suppressed (study 201) patients, respectively, with both showing significant declines in hepatitis B virus RNA, said Jacob Lalezari, MD, Quest Clinical Research, San Francisco, California, on April 13.

“Hepatitis B virus cure is a tremendous unmet medical need,” Dr. Lalezari said, “with >250 million people chronically infected with hepatitis B virus globally.”

The problem is that Nucs, the current standard of care, fail to fully eliminate virus or inhibit formation of covalently closed circular DNA, which is thought to be the form of the virus responsible for both chronic hepatitis B infection and persistent viral infection after antiviral treatment.

“Cure is not possible without elimination of residual virus,” stated Dr. Lalezari.

Core protein inhibitors block multiple steps in the viral replication cycle, achieve deeper levels of viral inhibition than Nucs alone, and can interdict formation of covalently closed circular DNA.

The double-blind phase 2a ABI-H0731 studies 201 and 202 enrolled 73 and 25 patients, respectively, with patients in the former receiving 3:2 standard-of-care Nuc therapy plus ABI-H0731 or Nuc plus placebo and those in the latter study receiving 1:1 entecavir plus ABI-H0731 or entecavir plus placebo. The primary endpoints were 24-week log10 decline in hepatitis B surface antigen/hepatitis B e-antigen for study 201 and log10 decline in hepatitis B virus DNA at weeks 12 and 24 in study 202.

Dr. Lalezari said that treatment was well tolerated, with no serious adverse events, treatment-related discontinuations, or interruptions in either study. Adverse events and laboratory abnormalities were generally considered unrelated to the study drugs.

Mean declines in hepatitis B virus DNA and RNA were significantly greater (faster and deeper) on combination therapy. In study 202, among treatment-naive hepatitis B e-antigen-positive subjects, the 2.27 and 2.54 declines in weeks 12 and 24, respectively, with the ABI-H0731-entecavir combination were significantly greater (P < .005/P< .005) than the 0.44 and 0.61 log10 declines with entecavir alone for hepatitis B RNA. Similarly, for hepatitis B DNA, the log10 declines at 12 and 24 weeks were significantly greater (P< .011/P< .005) for the combination (4.54 and 5.94, respectively) than for entecavir alone (3.29 and 3.99, respectively).

In study 201, among Nuc-suppressed hepatitis e-antigen-positive patients, mean log10 declines of RNA were significantly greater at 12 and 24 weeks for ABI-H0731-entecavir (2.34 and 2.20, respectively) than for Nuc alone (0.05 and 0.15, respectively). Also, 24-week assays of longitudinal serum samples showed residual declines below detection (2-5 IU/mL) only with the combination therapy.

Press conference moderator Markus Cornberg, Hannover Medical School, Hanover, Germany, commented, “It is great to see that new [hepatitis B virus] treatments are being developed. This hepatitis B core protein inhibitor shows an effect on hepatitis B virus RNA levels and thus an additional antiviral efficacy. However, it is too early to conclude if this treatment could lead to hepatitis B virus cure.”

[Presentation title: Interim Safety and Efficacy Results of the ABI-H0731 Phase 2a Program Exploring the Combination of ABI-H0731 With Nuc Therapy in Treatment-Naive and Treatment-Suppressed Chronic Hepatitis B Patients. Abstract LB-06]

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