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Positive Results Reported for Hepatitis D Drug Lonafarnib in Mid-Stage Trial
Positive results have been reported from a phase IIa study of lonafarnib in patients with chronic hepatitis delta virus (HDV) infection. The study was conducted at the National Institutes of Health Clinical Center in Bethesda, Maryland.
Lonafarnib is the first in a new class of antiviral agents known as prenylation inhibitors.
The double-blind, randomized, placebo-controlled, dose-ascending, proof-of-concept study evaluated treatment with two dosages of lonafarnib (100 mg twice daily [BID] and 200 mg BID) for 28 days.
A significant decrease in HDV RNA viral levels was observed after treatment with lonafarnib compared with placebo, including a statistically significant dose-dependent difference in the decline in HDV RNA virus between the 100 mg BID and 200 mg BID dosages compared with placebo. The decline in HDV RNA viral levels significantly correlated with serum lonafarnib drug levels.
Lonafarnib was generally well tolerated, with the most common adverse events in the treatment group being gastrointestinal-related.
Lonafarnib is a late-stage, orally active inhibitor of farnesyl transferase, an enzyme involved in the modification of proteins through a process called prenylation. HDV uses this host-cell process inside liver cells to complete a key step in its life cycle. Lonafarnib inhibits the prenylation step of HDV replication inside liver cells and blocks the virus’ ability to multiply. Since prenylation is a host process not under the control of HDV, and since lonafarnib inhibits prenylation, there is also a theoretical higher barrier to resistance with lonafarnib therapy, according to the drug’s developer (Eiger BioPharmaceuticals). Virus mutation, a common pathway to drug resistance, is not expected to be a potential pathway to lonafarnib resistance by HDV.
Hepatitis D is caused by infection with HDV and is considered to be the most severe form of viral hepatitis in humans. Hepatitis D occurs only as a co-infection in individuals with hepatitis B virus (HBV) infection, leads to more-severe liver disease than does HBV alone, and is associated with accelerated liver fibrosis, liver cancer, and liver failure. Approximately 15 million people worldwide have HDV infection. Globally, the infection is reported to be present in approximately 4% to 6% of chronic hepatitis B carriers.
Source: Eiger Biopharmaceuticals; December 22, 2014.