# Mathematical Modeling of HDV RNA, HBV DNA, and HBsAg Dynamics during Lonafarnib-Based Therapy: Insights from the LOWR HDV-1 Study

Source: [Mathematical Modeling of HDV RNA, HBV DNA, and HBsAg Dynamics during Lonafarnib-Based Therapy: Insights from the LOWR HDV-1 Study](<https://www.sota2.com/research/paper/6a2b9299d33dfb23e783b063>)

Collection index: [llms.txt](<https://www.sota2.com/research/llms.txt>)

Data updated: 2026-06-13T05:00:13.110Z

Authors: Adquate Mhlanga, Louis Shekhtman, Rami Zakh, Sarah Duehren, Ashish Goyal, Alexander Churkin, Vladimir Reinharz, Danny Barash, Jeffrey Glenn, Ohad Etzion, Scott J. Cotler, Cihan Yurdaydin, Harel Dahari

Published: 2026-06-11T14:16:09.000Z

## Abstract

Lonafarnib (LNF) is an investigational drug targeting hepatitis delta virus (HDV) but not hepatitis B virus (HBV), providing a unique opportunity to model HDV kinetics and how changes in HDV affect HBV. We performed a detailed kinetic analysis and developed a mathematical model to explain serum HBV DNA, HDV RNA and hepatitis B surface antigen (HBsAg) kinetics in 15 HBV/HDV coinfected patients receiving LNF-based treatment. After a delay of 0-2 days, patients experienced a rapid 1st-phase HDV-decline followed by either a viral plateau, 2nd slower-decline phase, or viral breakthrough (VB). LNF monotherapy led to a flat-partial-response (often followed by VB), while LNF combination therapy with ritonavir or pegylated interferon-$\\alpha$ (PEG-IFN$\\alpha$) was associated with a biphasic HDV decline (without VB). All treatments except LNF+PEG-IFN$\\alpha$ had at least one patient experiencing an increase in HBV on-treatment. Our model successfully reproduced the observed HDV and HBV kinetics. We estimated an HDV RNA half-life of 1.26 days \[95% confidence interval, CI: 1.05--1.47\] in serum and treatment efficacy of 94% in inhibiting HDV RNA production across all treatments \[95% CI: 89%--97%\], as reflected by the 1st phase HDV decline. The 2nd phase of HDV decline was explained by a time-dependent increase in efficacy, reaching a maximum of 98.9%. The model explained the increase in serum HBV DNA by a median 4-fold \[interquartile range, IQR: 1--28\] increase in HBV DNA production rate when HDV declined below an inhibitory threshold. The stability of serum HBsAg was explained by a constant number of HBsAg-producing cells.

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## Original sources and implementation

[Original paper](<https://arxiv.org/abs/2606.13386>)

[PDF](<https://arxiv.org/pdf/2606.13386.pdf>)