HBV Forum Overview

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Overview:

A platform for ongoing multi-stakeholder engagement, dialogue, and collaboration to advance the regulatory sciences for diagnosis and treatment of HBV and HBV/HDV co-infection, focusing on finite (curative) treatment. The hallmark of the Forum is the inclusion of all stakeholder groups, including patient and advocacy organizations, academia, federal agencies, industry, professional societies, and other relevant entities. The Forum works closely with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), providing a trans-Atlantic regulatory scope and breadth to the deliberations. In other words, our work brings pragmatic and practical results in the drug development process, keeping up with major regulatory policy advances, such as the 21st Century Cures Act and subsequent adaptations. More recently, we are engaging with regulatory authorities in Africa (South Africa, Zimbabwe, Nigeria, Egypt). The Forum’s contribution to resolving regulatory issues in our disease areas is well documented in consensus reports, collaborative analyses, and in standardized information sources.

Since 2016, the HBV Forum has convened experts in hepatology, virology, immunology, biomarker discovery/development, diagnostics, clinical research from academia, regulatory agencies, industry, patient organizations, research consortia such as ICE-HBV, and professional societies to discuss, deliberate and generate consensus on critical issues identified by HBV Forum members and prioritized by a Steering Committee of key opinion leaders. If warranted, these topics are taken up by working groups for output development which are often published in peer-reviewed journals as collaborative analyses, consensus reports, position statements, and more.


Goals:

  • provide scientific guidance to facilitate discussion between industry, regulatory agencies, the academic and patients’ communities and community advocates in the areas of HBV and HDV drug development.
  • facilitate evolving consensus, based on real-time scientific development in the areas of appropriate methodologies for novel therapeutics and diagnostics, clinical trial design and standardization of definitions.
Working Group Activities
 
Ongoing Working Groups Completed Working Groups
Immune Checkpoint Inhibitors Working Group to understand overall utility and clinical value from a riskbenefit perspective of anti-PD-1/anti-PD-L1 immune checkpoint inhibitors in a CHB patient population. This group conducted a literature review of immune-related adverse events (IrAEs) in cancer to understand the potential risks of IrAEs in a less advanced, potentially healthier (non-cancer) CHB patient population. To understand potential benefits, the group assessed publicly available data on clinical trials evaluating ICIs targeting PD-1-PD-L1 in CHB patient populations. These data were presented in a poster at The Liver Meeting 2024. Manuscript in Progress. HDV RNA Assays sub-Writing Group published a Review summarizing available research-based and commercial HDV RNA assays, discussing technical features of assays that result in substantial variability in performance characteristics, and outlining implications for the use of HDV RNA assays in drug development and patient monitoring of HDV RNA levels in trials.

Stopping Finite Therapies Working Group published a Viewpoints article on consensus in developing a framework for stopping novel agents and combination regimens for treatment of CHB when measuring offtreatment efficacy of investigational therapies.
Baseline Biomarker Working Group to determine the scope/breath of patient and viral heterogeneity in clinical trials to identify potential gaps and to contribute to our understanding of how this diversity may impact treatment response. This HBV Forum and Forum Data & Analysis Center collaboration entails collecting baseline biomarker data from completed phase 2 and phase 3 studies. Pharmaceutical sponsors are invited to share de-identified and/or anonymized baseline data. Forum staff have completed a clinical trials tracker and began to invite companies to join this project. Capsid Assembly Modulators Working Group published a joint statement on behalf of both the HBV Forum and ICE-HBV on standardizing nomenclature of core protein-targeting antivirals, promoting definition consensus.

Immune Monitoring Working Group published an article identifying a) a set of basic assays to facilitate cross-trial and cross-study comparison and b) biomarkers for immune-based interventions.
HDV Diagnostic Assay Development Working Group to facilitate development of HDV diagnostic assay development through collaboration in protocol design and biobank sample sharing. This working group is developing a protocol for assay development, with participation of all interested diagnostic manufacturers and non-industry HDV virology experts. Simultaneously, members are identifying sources of samples (US, EU and other countries with high HDV prevalence) for distribution among developers. The collaboration will ameliorate the challenges posed by scarce HDV sample availability and reduce cost/resources for everyone. Surrogate Endpoints Working Group published a meta-analysis to strengthen the link between surrogate markers and long-term clinical outcomes

Diagnostic/Biomarker sub-Working Group to develop clarity on what is needed for biomarker acceptance and validation for HBV drug/diagnostic development. Created the “Inventory of diagnostics approval status by US-FDA and the EU”.
MAPPED Working Group (Mechanisms of Action and Patient Populations: Emphasizing Diversity) to contribute to understanding of recent HBV program failures by consideration of how diversity of patients and different mechanisms of action could be leveraged for better trial outcomes. Manuscript in progress.

Standardizing HBV Nomenclature Working Group to facilitate a reassessment and potential standardization of nomenclature for HBV disease stages to support the clinical practice and therapeutic development fields. Manuscript in progress to outline current nomenclature challenges and call for collaboration amongst liver societies, the patient community, and other groups.		 Treatment Combination Working Group to provide clarity on the requirements of novel agents in clinical development and to identify mechanisms to speed up the development of combination of different promising agents across companies.

Liver Safety Monitoring sub-Working Group published an article to facilitate consensus on terminology and definitions to use when testing the safety and efficacy of novel therapeutic agents for chronic HBV when used alone or in combination with other investigational or approved anti-HBV agents.
HBV-HDV Clinical Research in Africa Working Group to facilitate and promote HBV and HDV drug and diagnostic development in Africa. Working together with Africa-based and global hepatitis organizations, we foster collaboration among existing clinical research networks, African organizations (regulatory authorities, community organizations, national agencies), highlight the benefits that clinical research participation brings to affected communities, and the opportunities for accelerating access through more efficient registration of new therapeutics and diagnostics across the continent.