Dicerna Announces Dosing of First Patient in Phase 1 Clinical Trial of DCR-HBVS for the Treatment of Chronic Hepatitis B Virus
May 16, 2019
— Clinical Proof-of-Concept Data Expected in Fourth Quarter of 2019 —
“Dosing of the first patient in the DCR-HBVS-101 trial signals a major
step toward our ultimate goal of developing a viable therapeutic option
for patients with chronic hepatitis B virus, a serious liver infection
that can result in advanced liver disease or liver cancer if not treated
The DCR-HBVS-101 clinical trial is a Phase 1, randomized, placebo-controlled study designed to evaluate the safety and tolerability of DCR-HBVS in healthy volunteers (HVs) and in patients with non-cirrhotic chronic HBV infection. Secondary objectives are to characterize the pharmacokinetic profile of DCR-HBVS and to evaluate preliminary pharmacodynamics and antiviral efficacy on plasma levels of hepatitis B surface antigen (HBsAg) and HBV DNA in blood.
DCR-HBVS is comprised of a single GalXC molecule that targets HBV messenger RNAs within the HBsAg gene sequence region. Preclinical studies with a standard mouse model of HBV infection showed DCR-HBVS led to greater than 99% reduction in circulating HBsAg, suggesting a level of HBsAg suppression (both in magnitude and duration of suppression) that may be greater than that achieved from targeting within the X gene sequence region.
“Given the encouraging inhibitory activity of DCR-HBVS in animal
studies, its favorable preclinical safety profile, and the lack of major
safety signals among healthy volunteers dosed thus far in the
DCR-HBVS-101 trial, we eagerly anticipate the results from patients with
chronic hepatitis B who are treated with DCR-HBVS,” said
DCR-HBVS-101 Trial Design
The DCR-HBVS-101 clinical trial is divided into three phases or groups:
- In Group A, 30 HVs are to receive a single ascending-dose of DCR-HBVS (0.1, 1.5, 3, 6, or 12 mg/kg) or placebo, with a four-week follow-up period.
- Group B is a single-dose arm in which eight participants with HBV who are naïve to nucleoside analog therapy will receive a 3 mg/kg dose of DCR-HBVS or placebo; these participants will be followed for at least 12 weeks. The Company expects to initiate Group B dosing in the third quarter of 2019, in parallel with Group C at the 3 mg/kg dose level.
- Group C is a multiple ascending dose arm in which DCR-HBVS (1.5, 3, or 6 mg/kg) or placebo will be administered to 18 participants with HBV who are already being treated with nucleoside analogs, with a treatment and follow-up period of 16 weeks or more. The first participant dosed was from this group, at a dose of 1.5 mg/kg.
Study participants in Groups B and C, in whom HBsAg will have dropped by more than 1 log10 IU/mL below baseline at their last scheduled study visit, will continue to be followed until their HBsAg level is less than 1 log10 IU/mL below the baseline value.
For more information about the DCR-HBVS-101 clinical trial, please visit www.clinicaltrials.gov and use the identifier NCT03772249.
About Chronic Hepatitis B Virus (HBV) Infection
Hepatitis B virus (HBV) is the world’s most common serious liver
infection, with more than 292 million patients chronically infected,
according to an estimate by the
DCR-HBVS is an investigational drug in development for the treatment of chronic hepatitis B virus (HBV) infection. Current therapies for HBV, such as nucleoside analogs and pegylated interferon, aim to suppress the virus; however, although these treatments can provide long-term viral suppression if taken continuously, they rarely lead to a long-term functional cure, as measured by the clearance of HBV surface antigen (HBsAg) and sustained HBV deoxyribonucleic acid (DNA) suppression in patient plasma or blood. By contrast, DCR-HBVS targets HBV messenger RNA (mRNA) and leads to greater than 99% reduction in circulating HBsAg, as observed in mouse models of HBV infection. Those data suggest that DCR-HBVS may induce long-term clearance of intrahepatic and serum HBsAg.
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements. Such
forward-looking statements are subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statements. Examples of forward-looking statements
include, among others, statements we make regarding: (i) the enrollment
and successful screening of patients in the Phase 1 clinical trial of
DCR-HBVS; (ii) the expectation of human proof-of-concept data from the
Phase 1 trial in the fourth quarter of 2019; (iii) the therapeutic and
commercial potential of the GalXC™ platform, including DCR-HBVS; (iv)
research and development plans and timelines related to GalXC, including
DCR-HBVS; and (v) the potential of our technology and drug candidates in
our research and development pipeline. The process by which an early
stage investigational therapy such as DCR-HBVS and an early stage
platform such as GalXC could potentially lead to an approved product is
long and subject to highly significant risks. Applicable risks and
uncertainties include those relating to our clinical research and other
risks identified under the heading "Risk Factors" included in our most
recent Form 10-Q filing and in other future filings with the
Hepatitis B Foundation. Facts and Figures. 2019. Available at: http://www.hepb.org/what-is-hepatitis-b/what-is-hepb/facts-and-figures/. Accessed on January 17, 2019.