Date: 2015-04-27
Type of information: Interim results
phase: 2
Announcement: interim results
Company: Eiger Biopharmaceuticals (USA - CA)
Product: lonafarnib
Action
mechanism: farnesyl transferase inhibitor. Lonafarnib is a late stage, orally active agent targeting farnesyltransferase, an enzyme involved in modification of proteins through a process called prenylation. Hepatitis delta virus uses this host cellular 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 life cycle at the stage of assembly. Since prenylation is carried out by a host enzyme there is a theoretical higher barrier to develop viral resistance mutations to lonafarnib therapy. Lonafarnib has been granted Orphan Drug Designation by the FDA and the European Medicines Agency (EMA), and Fast Track designation by US FDA. It is licensed from Merck & Co.
Disease: hepatitis delta viral (HDV) infection
Therapeutic area: Infectious diseases
Country: Turkey
Trial
details: LOWR-1 is an open-label, dose-ranging, proof-of-concept study to evaluate the safety and efficacy of fonafarnib with and without ritonavir boosting in patients chronically infected with delta hepatitis (HDV) (NCT02430181). LOWR-2 is an open-label, dose-ranging study to evaluate the safety and efficacy of fonafarnib with ritonavir boosting in patients chronically infected with delta hepatitis (NCT02430194).
Latest
news: * On April 27, 2015, Eiger BioPharmaceuticals announced the presentation of interim results of Phase 2 data of lonafarnib in patients with chronic hepatitis delta viral (HDV) infection. Data were presented from the LOWR HDV program, enrolled at Ankara University Medical School, Turkey, in a country where HDV is endemic. LOWR HDV - 1 (LOnafarnib With and without Ritonavir-1) is a parallel dose comparison study which randomized subjects to receive different doses of lonafarnib with or without ritonavir or pegylated interferon for four to twelve weeks. Interim data from 15 subjects who received lonafarnib alone or with ritonavir boosting or in combination with pegylated interferon all led to decreased viral loads. High doses (200 mg twice daily or 300 mg twice daily) of lonafarnib resulted in 1.6 and 2.0 log decline in viral loads after 4 weeks of treatment, respectively. A lower dose of lonafarnib (100 mg twice daily) with 100 mg daily ritonavir boosting or in combination with 180 mcg once weekly of pegylated interferon resulted in a 2.2 and a 1.8 log decline in viral load at week 4, respectively. At week 8, the mean viral load declines were 3.2 and 3.0 logs for subjects on lonafarnib with ritonavir or lonafarnib with pegylated interferon, respectively. The most frequently observed adverse events in LOWR-1 were anorexia, nausea, diarrhea, fatigue, and weight loss, and these appeared to be dose-dependent. LOWR HDV - 2 (LOnafarnib With Ritonavir-2) was recently initiated to test a range of doses of lonafarnib boosted by ritonavir, with the aim to identify optimal combination(s) for the next longer-term studies. \"The data generated thus far investigating lonafarnib combinations are very encouraging,\" said Cihan Yurdaydin, MD, Principal Investigator, Ankara University Medical School. \"We continue to conduct dose finding with lonafarnib boosted by ritonavir to identify the optimal balance of efficacy and tolerability, with a goal of viral clearance.\"
