Conference Coverage

HDV combo therapy reduces viral loads



– For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.

After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.

The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).

The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.

After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.

Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.

According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.

“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.

The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.

SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.

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