Statistically significant virologic and biochemical responses were observed in patients with chronic hepatitis delta virus (HDV) treated with lonafarnib-based regimens, according to topline results from the D-LIVR study.
In the phase 3 study (ClinicalTrials.gov Identifier: NCT03719313), patients were randomly assigned to receive either lonafarnib boosted with ritonavir (all-oral; n=178), lonafarnib boosted with ritonavir combined with peginterferon alfa (combination; n=125), or placebo (n=52). The primary endpoint was a composite of virologic and biochemical response rate (≥2 log decline in HDV RNA and alanine aminotransferase [ALT] normalization) at the end of the 48 week treatment period.
Findings showed that the all-oral and combination treatment arms demonstrated statistically significant composite responses of 10.1% (P =.0044) and 19.2% (P <.0001), respectively, compared with the placebo arm (1.9%). Virologic response was achieved by 14.6% (P =.0026) and 32% (P <.0001) of patients in the all-oral and combination treatment arms, respectively, compared with 3.8% of those in the placebo arm.
Moreover, ALT normalization was achieved by 24.7% (P =.003) and 34.4% (P <.0001) of patients in the all-oral and combination treatment arms, respectively, compared with 7.7% of those in the placebo arm. Statistically significant improvement in histological response rate (key secondary endpoint) was observed in patients treated with the combination therapy vs placebo.
The study also included a peginterferon alfa comparator arm (n=52). Findings showed a comparable composite response in the all-oral arm and the peginterferon alfa arm (10.1% vs 9.6%, respectively), while in the combination arm, the composite response was twice that of the peginterferon alfa arm (19.2% vs 9.6%, respectively).
Gastrointestinal side effects were reported to be the most frequent treatment emergent adverse events associated with the lonafarnib regimens.
“The results of this landmark study highlight 3 key findings,” said Ohad Etzion, MD, Director, Department of Gastroenterology and Liver Diseases at Soroka University Medical Center and D-LIVR study co-lead investigator. “First, a small subset of patients with chronic HDV infection may achieve virologic and biochemical improvements with an all-oral regimen after 48 weeks of treatment. Second, combining lonafarnib and ritonavir with peginterferon alfa demonstrated the potential to nearly double the response rate. And third, and perhaps most importantly, based on these data, combination treatment may lead to significant histologic improvement, a generally accepted surrogate for improved future clinical outcomes for patients.”
Additional data, including an analysis of a 24-week post treatment follow up, are expected to be reported in mid-2023.
Eiger announces both lonafarnib-based treatments in pivotal phase 3 D-LIVR trial in hepatitis delta virus (HDV) achieved statistical significance against placebo in composite primary endpoint. News release. Eiger. Accessed December 8, 2022. https://www.prnewswire.com/news-releases/eiger-announces-both-lonafarnib-based-treatments-in-pivotal-phase-3-d-livr-trial-in-hepatitis-delta-virus-hdv-achieved-statistical-significance-against-placebo-in-composite-primary-endpoint-301698023.html.