Skip to main content
 
Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
Stanford Health Care

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study HEPATOLOGY Yurdaydin, C., Keskin, O., Kalkan, C., Karakaya, F., Caliskan, A., Karatayli, E., Karatayli, S., Bozdayi, A., Koh, C., Heller, T., Idilman, R., Glenn, J. S. 2018; 67 (4): 1224–36

Abstract

In a proof-of-concept (POC) study, the oral prenylation inhibitor, lonafarnib (LNF), decreased hepatitis D virus (HDV) RNA during 4 weeks of treatment. Here, we explored optimal LNF regimens. Fifteen patients (five groups; 3 per group) completed dosing as follows: (1) LNF 200?mg twice-daily (BID; 12 weeks); (2) LNF 300?mg BID (12 weeks); (3) LNF 100?mg thrice-daily (5 weeks); (4) LNF 100?mg BID?+?pegylated interferon alfa (PEG-IFNa) 180?µg once-weekly (QW; 8 weeks); and (5) LNF 100?mg BID?+?ritonavir (RTV) 100?mg once-daily (QD; 8 weeks). Tolerability and efficacy were assessed. Higher LNF monotherapy doses had greater decreases in HDV viral load than achieved in the original POC study. However, this was associated with increased gastrointestinal adverse events. Addition of RTV 100?mg QD to a LNF 100?mg BID regimen yielded better antiviral responses than LNF 300?mg BID monotherapy and with less side effects. A similar improvement was observed with LNF 100?mg BID?+?PEG-IFNa 180?µg QW. Two of 6 patients who received 12 weeks of LNF experienced transient posttreatment alanine aminotransferase (ALT) increases resulting in HDV-RNA negativity and ALT normalization.The cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG-IFNa achieved more substantial and rapid HDV-RNA reduction, compared to historical responses with PEG-IFNa alone. Twelve weeks of LNF can result in posttreatment HDV-RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG-IFN. (Hepatology 2018;67:1224-1236).

View details for DOI 10.1002/hep.29658

View details for Web of Science ID 000428332600010

View details for PubMedID 29152762