In patients with chronic delta hepatitis, lonafarnib (oral prenylation inhibitor), boosted with low dose ritonavir, is a promising all-oral therapeutic choice with maximal efficacy attained with the  addition of pegylated interferon alfa, as elucidated from single-center, open-label, phase II, dose-finding study published in Hepatology.

In the LOnafarnib With Ritonavir for HDV-2 (LOWR-2) study, the optimal combination of  ritonavir + lonafarnib ± pegylated interferon alfa with tolerability and effectiveness for long-term dosing was identified. This study aimed to investigate the effectiveness and safety at the end of therapy for up to twenty-four weeks in 55 people suffering from chronic hepatitis delta virus (HDV).

Participants were segregated into three groups: (i) High dose lonafarnib group (lonafarnib ≥ 75 mg orally twice a day + ritonavir; N=19; 12 weeks); (ii) All-oral low dose lonafarnib group (lonafarnib 25 or 50 mg orally twice a day + ritonavir; N=24; 24 weeks), and (iii) Combination of low dose lonafarnib with pegylated interferon alfa group (lonafarnib 25 or 50 mg orally twice a day + ritonavir + pegylated interferon alfa; N=12; 24 weeks).

The major outcome was  ≥ 2 log₁₀ decline or < lower limit of quantification (LLOQ) of HDV-RNA from the baseline at the end of treatment. Table 1 shows the percentage of participants achieving the major outcome.

Furthermore, multiple participants had well-tolerated transient post-therapy alanine aminotransferase (ALT) rise leading to alanine aminotransferase normalization and HDV RNA negativity. The percentage of grade II and III gastrointestinal side effects in the low vs. high dose groups were 22% (18/81) and 49% (37/76), respectively. The identified optimal regimens favor the first phase III (D-LIVR) study of lonafarnib to manage HDV.