Dasabuvir

證據等級: L5

預測適應症: 5 個

Dasabuvir: From Hepatitis C Virus Infection to Hepatitis B Virus Infection

One-Sentence Summary

Dasabuvir (ABT-333) is a direct-acting antiviral originally used for chronic Hepatitis C Virus (HCV) Genotype 1 infection as part of the Viekira Pak combination regimen (ombitasvir/paritaprevir/ritonavir + dasabuvir). The TxGNN model predicts it may be effective for Hepatitis B Virus (HBV) infection with a prediction score of 99.37% (rank 9,325 overall). However, no clinical trials have directly evaluated dasabuvir for HBV treatment, and available literature only documents HBV as a safety monitoring endpoint during HCV co-infection therapy — yielding an L5 evidence level and a Hold recommendation.

Quick Overview

Item	Content
Original Indication	Chronic HCV Genotype 1 infection (inferred from drug class; no Saudi Arabia regulatory records available)
Predicted New Indication	Hepatitis B Virus (HBV) Infection
TxGNN Prediction Score	99.37%
Evidence Level	L5 (model prediction only; no direct clinical studies)
Saudi Arabia Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available from current regulatory records. Based on known pharmacological information, dasabuvir (development code ABT-333) is a non-nucleoside NS5B RNA-dependent RNA polymerase (RdRp) inhibitor that binds the thumb II allosteric pocket of the HCV NS5B protein. It is used exclusively in combination with ombitasvir/paritaprevir/ritonavir (Viekira Pak / Exviera), achieving sustained virological response (SVR12) rates exceeding 95% in HCV Genotype 1b patients.

The TxGNN model assigns a high score because HCV and HBV share substantial phenotypic overlap — both are hepatotropic viruses causing chronic liver disease, cirrhosis, and hepatocellular carcinoma risk, and they share transmission routes and patient populations. This disease-level proximity in the knowledge graph drives a strong association. Several trials in this evidence pack reflect how commonly patients are co-infected with both viruses.

However, pharmacological mechanism transferability is very limited. HBV replicates through a reverse transcriptase (RT) pathway encoded by its DNA polymerase, which is mechanistically and structurally distinct from the HCV NS5B RdRp. The thumb II allosteric binding pocket that dasabuvir occupies has no structural homologue in HBV reverse transcriptase. Established HBV antivirals (tenofovir, entecavir) work through nucleoside RT inhibition — a mechanism dasabuvir does not possess. The TxGNN high score reflects graph topology (hepatitis disease clustering), not validated pharmacological applicability to HBV.

Clinical Trial Evidence

All 14 retrieved trials evaluated dasabuvir in the context of HCV treatment. No trial has directly assessed dasabuvir's efficacy against HBV. The single most relevant trial (Grade B) monitored HBV only as a safety endpoint.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02555943	Phase 2/3	Completed	23	HCV/HBV co-infected patients receiving DAA therapy; primary endpoint was HCV SVR; HBV reactivation monitored as a safety indicator only — no anti-HBV efficacy evaluation
NCT01854697	Phase 3	Completed	311	MALACHITE-I: ABT-450/r/ombitasvir + dasabuvir vs telaprevir/pegIFN/RBV in treatment-naïve HCV GT1; no HBV component
NCT01939197	Phase 2/3	Completed	318	TURQUOISE-I: ombitasvir/paritaprevir/r ± dasabuvir ± RBV in HCV GT1/4 + HIV-1 co-infection; HCV SVR12 as primary endpoint, no HBV data
NCT02219477	Phase 3	Completed	36	TURQUOISE-CPB: OBV/PTV/r + dasabuvir + RBV in HCV GT1 decompensated cirrhosis; HCV safety and SVR12 only
NCT03423641	N/A	Completed	33,808	Post-marketing safety surveillance of DAA medications for HCV (including dasabuvir regimens); large observational study, HCV population only
NCT01995071	Phase 2	Completed	89	Dose-ranging study of ABT-493 and ABT-530 in HCV GT1; antiviral activity assessment in HCV, no HBV arm
NCT01464827	Phase 2	Completed	580	ABT-450/r ± ABT-267 ± dasabuvir ± RBV for 8–24 weeks in HCV GT1; evaluates antiviral activity and PK of dasabuvir combination
NCT01782495	Phase 2	Completed	129	CORAL-I: ABT-450/r/ombitasvir + dasabuvir ± RBV in liver or renal transplant recipients with HCV GT1/4; transplant special population, HCV-focused
NCT02493855	Phase 2	Completed	46	Viral load kinetics with OBV/ABT-450/r + dasabuvir ± ribavirin in HCV GT1a treatment-naïve; exploratory PK/PD study, no HBV
NCT00851890	Phase 2	Completed	30	Early dasabuvir (ABT-333) safety, tolerability, PK, and antiviral activity study in HCV GT1 patients; foundational dasabuvir characterization

None of the 14 retrieved trials include an HBV treatment arm or endpoint. Evidence level for dasabuvir in HBV: L5.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
29397016	2018	Cohort	J Viral Hepatitis	HBV reactivation risk in HBV+HCV co-infected cirrhosis patients (N=2,070 HCV) treated with ombitasvir/paritaprevir/r + dasabuvir + RBV; HBV monitored as safety concern, no anti-HBV efficacy data
28416221	2017	RCT	Lancet Gastroenterol Hepatol	GARNET Phase 3b: OBV/PTV/r + dasabuvir for 8 weeks in HCV GT1b without cirrhosis; high SVR12 rates confirmed; HCV efficacy only
28903508	2017	RCT Analysis	Clin Infect Dis	PrOD and ledipasvir/sofosbuvir regimens confer significant mortality benefit vs untreated HCV in a large VA cohort; demonstrates overall clinical value of dasabuvir-containing regimens
28762541	2018	Real-world Cohort	J Gastroenterol Hepatol	Real-world effectiveness and safety of PrOD in Taiwan HCV GT1b patients; confirms high SVR rates in East Asian population with HCV; no HBV data
25529080	2015	Review	Liver Int	Discusses pathways toward HCV eradication and HBV cure; highlights mechanistic distinctions between HCV DAAs and HBV antivirals and the separate drug development requirements
36515288	2022	Epidemiology	Voprosy Virusologii	HBV, HCV, and HDV prevalence and molecular genetic characterization in HIV-positive patients; illustrates HBV/HCV co-infection epidemiology relevant to co-infection treatment context
26043288	2015	Review	Rev Med Virol	Comprehensive review of HCV DAA development targeting NS3/4A, NS5A, and NS5B; explains dasabuvir's non-nucleoside NS5B inhibitor class and mechanism — highlights HCV specificity
30964552	2019	In vitro/Resistance	Hepatology	HCV protease inhibitor resistance-associated substitutions across major genotypes; resistance mechanisms in HCV context, relevant to understanding dasabuvir combination partner durability
26139639	2015	Review	Ann Pharmacother	Treatment considerations for special HCV GT1 populations (renal impairment, transplant, HIV co-infection) using dasabuvir-containing regimens; no HBV therapeutic discussion
28992878	2017	Review	Hepatobiliary Pancreatic Dis Int	Peginterferon alfa-2a role in the DAA era for HCV; contextualizes DAA positioning including dasabuvir regimens in markets with access constraints

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: Dasabuvir's mechanism of action — inhibiting the HCV NS5B thumb II allosteric pocket — has no structural equivalent in HBV, which replicates through a reverse transcriptase pathway that existing nucleoside/nucleotide analogues (tenofovir, entecavir) already address effectively. The TxGNN score of 99.37% reflects graph-based disease proximity between viral hepatitides, not mechanistically supported repurposing potential. With zero relevant clinical trials, no direct literature evidence, no Saudi Arabia market presence, and missing safety data, this candidate does not meet the threshold for further development investment at this time.

To proceed, the following is needed:

Preclinical mechanistic assessment: In vitro evaluation of dasabuvir against HBV DNA polymerase/RT activity, and computational docking analysis of the dasabuvir binding pose against HBV RT crystal structures
MOA documentation: Full DrugBank API retrieval for NS5B binding characterization, selectivity profile, and any reported cross-reactivity data against other viral polymerases
Safety profile: Obtain full package insert warnings and contraindications (SFDA/EMA/FDA label) to complete S1 safety screening — currently blocking formal safety evaluation
Mechanistic reconsideration: Given the structural mismatch between HCV NS5B and HBV RT, a formal mechanistic review should determine whether any indirect antiviral pathway (e.g., host immune modulation observed post-SVR) could justify continued investigation, or whether resources should be redirected to better-supported HBV repurposing candidates
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.