AMSTERDAM — Lower doses of Sarasar, used in combination with ritonavir and pegylated interferon, effectively suppressed hepatitis delta virus and seemed to normalize ALT, according to a presenter at the International Liver Congress.
“Based on the data I have provided here, we recommend that all-oral low dose combination and triple therapy with lonafarnib 25 mg [twice daily] should be considered for further development,” Cihan Yurdaydin, MD, chair in gastroenterology at the University of Ankara Medical School and chief of the Hepatology Institute, University of Ankara, said during his presentation.
In this LOWR-2 study, Yurdaydin and colleagues looked to identify what combinations, treatment durations and what doses would be most effective in treating the rare disease.
In this presentation, Yurdaydin focused on 24- and 48-week treatments with the all-oral lower dosing of Sarasar (lonafarnib, Eiger Biopharmaceuticals) with ritonavir and the triple combination of lonafarnib in the same dosing but in combination with ritonavir and PEG-IFN.
At week 24 in the all-oral 25 mg lonafarnib group, three of six patients showed HDV RNA lower than the limit of quantification (LOQ), none were PCR negative and three had a log decline more than 2. In the 50-mg group, two of eight showed HDV RNA lower than LOQ, one was PCR negative and one had a log decline more than 2.
At week 24 in the PEG-IFN triple therapy group with 25 mg lonafarnib, four out of five had HDV RNA less than LOQ, three were PCR negative and three had a log decline greater than 2. In the 50-mg triple therapy group, three of four had HDV RNA less than LOQ, none were PCR negative and three had a log decline greater than 2.
“At 24 weeks of treatment, all oral lonafarnib 25 and 50 mg [twice daily] and ritonavir suppressed HDV RNA below the lower limit of quantification in 36% of patients,” Yurdaydin said. “The addition of PEG-IFN enhanced antiviral activity.”
When treatment was continued through 48 weeks, Yurdaydin showed that three of seven patients (43%) had HDV RNA lower than LOQ while 67% of patients treated with triple therapy including 25 mg lonafarnib were PCR negative at 48 weeks.
At baseline, ALT was elevated in all patients across both groups. At week 24, 60% of patients treated with the all-oral regimen showed normalized ALT. In the triple regimen, 78% showed normalized ALT at week 24.
Adverse events were mild to moderate and included anorexia, nausea, vomiting, weight loss and diarrhea, Yurdaydin said. – by Katrina Altersitz
Yurdaydin C. GS-008. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.
Disclosure: Yurdaydin reports no relevant financial relationships.