Chronic Hepatitis B Finite Treatment: Similar and Different Concerns With New Drug Classes.

Chronic hepatitis B, a major cause of liver disease and cancer, affects >250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative hepatitis B virus (HBV) therapies are underway, consisting of combinations of multiple novel agents with or without nucleos(t)ide reverse-transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, along with subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives, and regulatory agencies. This Viewpoints article outlines areas of consensus within our multistakeholder group for stopping finite therapies in chronic hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, predefined stopping criteria, predefined retreatment criteria, duration of investigational therapies, and follow-up after stopping therapy. Future research of unmet needs are discussed.

HDV RNA assays: Performance characteristics, clinical utility, and challenges.

Coinfection with HBV and HDV results in hepatitis D, the most severe form of chronic viral hepatitis, frequently leading to liver decompensation and HCC. Pegylated interferon alpha, the only treatment option for chronic hepatitis D for many years, has limited efficacy. New treatments are in advanced clinical development, with one recent approval. Diagnosis and antiviral treatment response monitoring are based on detection and quantification of HDV RNA. However, the development of reliable HDV RNA assays is challenged by viral heterogeneity (at least 8 different genotypes and several subgenotypes), intrahost viral diversity, rapid viral evolution, and distinct secondary structure features of HDV RNA. Different RNA extraction methodologies, primer/probe design for nucleic acid tests, lack of automation, and overall dearth of standardization across testing laboratories contribute to substantial variability in performance characteristics of research-based and commercial HDV RNA assays. A World Health Organization (WHO) standard for HDV RNA, available for about 10 years, has been used by many laboratories to determine the limit of detection of their assays and facilitates comparisons of RNA levels across study centers. Here we review challenges for robust pan genotype HDV RNA quantification, discuss particular clinical needs and the importance of reliable HDV RNA quantification in the context of drug development and patient monitoring. We summarize distinct technical features and performance characteristics of available HDV RNA assays. Finally, we provide considerations for the use of HDV RNA assays in the context of drug development and patient monitoring.

Twenty-five years of addressing cutting-edge scientific, policy, and regulatory issues through collaboration: The Forum for Collaborative Research.

Developing safe and effective drugs and other medical products is a complex and costly process. Drug development has been, historically, commonly competitive and uncollaborative, and this tendency toward a lack of interaction between stakeholders-the pharmaceutical industry, academia, regulatory agencies, healthcare providers, and communities, among others-can lead to missed opportunities to improve efficiency and, ultimately, public health. The Forum for Collaborative Research was established in 1997 to address current scientific, policy, and regulatory issues in global health through multistakeholder engagement and dialogue. By providing a neutral and safe space for discussion, the Forum's model has impacted how clinical trials in diverse health areas are conducted, supported broader and more equitable clinical trial participation, and accelerated delivery of new drugs. The Forum's focus and directions have shifted over time, and this responsiveness to the needs of the global health community will be critical to ensure that the Forum continues to support collaboration in global health. In this article, we present lessons learned from this innovative model of collaborative research and regulatory science, pioneered by the Forum for over 25 years, including the importance of collective ownership and governance by all stakeholders, and emphasis on common goals and advantages of collaboration.