SARASAR® (lonafarnib) Clinical Studies

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SARASAR® (lonafarnib) Clinical Studies 2017-02-07T21:50:57+00:00

Phase 2a Study: NIH Phase 2 POC Study

Lonafarnib has been studied in a Phase 2a trial in patients with chronic hepatitis delta viral (HDV) infection. This NIH-conducted, double-blinded, randomized, placebo-controlled, dose ascending study evaluated two doses of lonafarnib, 100 mg twice daily and 200 mg twice daily for 28 days.  This proof-of-concept study is the first ever to evaluate lonafarnib, the first of a class of novel antiviral prenylation inhibitors, in patients infected with HDV.

A dose-dependent decrease in HDV RNA levels of 0.7 log IU/mL at 100 mg BID and 1.6 log IU/mL in the 200 mg BID arm compared to a 0.08 log IU/mL decrease in the placebo patients after 28 days of treatment was observed.  The decline in HDV RNA viral levels correlated with serum lonafarnib drug levels, providing further evidence for the efficacy of lonafarnib in chronic HDV.  In the study, lonafarnib was generally tolerated, with the most common adverse events in the treatment group being mild to moderate nausea and diarrhea.

Phase 2a Study Figure 1
Phase2aStudy-Graphic2

Eiger reported top-line results from the Phase 2a trial in November 2014 at the American Association of the Study of Liver Diseases (AASLD).  Results were published in 2015 (Koh C et al Lancet Infect Dis 2015; 15: 1167-74).

Phase 2 Study: LOWR HDV – 1

Lonafarnib has been studied in a Phase 2 trial in patients with chronic hepatitis delta viral (HDV) infection in Ankara, Turkey.  LOWR HDV – 1 (LOnafarnib With and without Ritonavir in Hepatitis Delta Virus-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. Lonafarnib is extensively metabolized by CYP3A4. Boosting lonafarnib with ritonavir was predicted to increase serum concentrations of lonafarnib, allowing for lower doses of lonafarnib to be administered.  Combinations of lonafarnib with pegylated interferon allows for evaluating additive effects of the two drugs.

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 HDV – 1 were anorexia, nausea, diarrhea, fatigue, and weight loss, and these appeared to be dose-dependent.

Eiger reported top-line results from the Phase 2 trial in April 2015 at the European Association for the Study of the Liver (EASL).

See clinicaltrials.gov: NCT02430181

Week 4 Reduction HDV

Phase 2 Study: LOWR HDV – 2

LOWR HDV – 2 (LOnafarnib With Ritonavir in Hepatitis Delta Virus-2) is a dose-finding Phase 2 study 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.  LOWR HDV – 2 is being conducted at Ankara University in Turkey and is currently enrolling patients. Eiger reported interim results from this on-going Phase 2 trial at the 2016 European Association for the Study of the Liver (EASL) meeting.

For more information, please visit clinicaltrials.gov: NCT02430194

Phase 2 Study: LOWR HDV – 3

LOWR HDV – 3 (LOnafarnib With Ritonavir in Hepatitis Delta Virus-3) is a Phase 2, randomized, placebo-controlled study of multiple once a day doses of lonafarnib boosted by ritonavir, with the aim to identify an optimal combination(s) for Phase 3 studies. LOWR HDV – 3 is being conducted at the NIH and dosing has been completed.

For more information, please visit clinicaltrials.gov: NCT02511431

Phase 2 Study: LOWR HDV – 4

LOWR HDV – 4 (LOnafarnib With Ritonavir in Hepatitis Delta Virus-4) is a Phase 2, open-label, dose-titration study of multiple twice a day doses of lonafarnib boosted by ritonavir, with the aim to identify optimal combination(s) for Phase 3 studies. LOWR HDV – 4 is being conducted at Hannover Medical School in Germany. LOWR HDV – 4 is being conducted at the NIH and dosing has been completed.

For more information, please visit clinicaltrials.gov: NCT02527707

Hepatitis Delta (HDV)

HDV Slide