Emerging treatments
Lonafarnib
Lonafarnib, a prenylation inhibitor, inhibits the farnesyl transferase that is involved in modifying the hepatitis D virus (HDV) antigen so that it can be incorporated into the hepatitis B virus surface antigen (HBsAg). The efficacy of lonafarnib was demonstrated in a small pilot study of 14 patients with chronic HDV infection, followed over 28 days, with a dose-dependent drop in HDV RNA levels that correlated with the lonafarnib serum concentration.[62] By adding ritonavir (a protease inhibitor) to boost the lonafarnib serum level, the antiviral response improved and the gastrointestinal adverse effects decreased. Adding peginterferon alfa improved the antiviral effect further.[63] The D-LIVR study, which is yet to be published, randomised 407 patients with chronic HDV infection to receive lonafarnib boosted with ritonavir alone (all-oral) or in combination with peginterferon alfa (combination). The composite primary endpoint was a ≥2 log decline in HDV RNA and normalisation of alanine transaminase at the end of 48 weeks of treatment compared with placebo. Patients on the all-oral therapy and combination therapy showed a composite response of 10.1% (P=0.0044) and 19.2% (P <0.0001), respectively, compared with those receiving placebo (1.9%).[64] Similarly, histological response (defined as ≥2-point improvement in histological activity index and no worsening of Ishak fibrosis scoring) improved with treatment in 35 of 66 patients (53%, P=0.0139) in the combination group versus 8 of 30 patients (27%) receiving placebo. Lonafarnib has been granted orphan drug designation in some countries for the treatment of HDV infection, and is approved in some countries for other indications.
Tobevibart/elebsiran
The combination of tobevibart (an investigational monoclonal antibody) and elebsiran (an investigational small interfering RNA) has been granted fast-track designation by the US Food and Drug Administration, following positive preliminary phase 2 trial data. The phase 2 clinical trial is ongoing.[65]
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