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‘Quest for better HDV therapy’: triple combination reduces RNA in most

BOSTON — Triple combination therapy with lonafarnib, ritonavir, and Lambda for chronic hepatitis D appeared safe and tolerable for up to 6 months in most patients and led to high rates of RNA decline, according to data presented at The Liver Meeting 2019.

“Worldwide, approximately 15 to 20 million people are infected with delta hepatitis, and up to 80% of those patients may develop cirrhosis within 5 to 10 years,” Christopher Koh, MD, MHSc, FAASLD, from National Institutes of Health in Maryland, said during his presentation. “Patients with delta hepatitis are at a higher risk for hepatic decompensation, leading to death and the development of hepatocellular carcinoma compared with monoinfected hepatitis B patients.”

Koh explained that previous experience with interferon alpha in HDV has been unsatisfactory with less than 30% of patients who achieved HBV surface antigen loss and became HDV RNA negative. Additionally, nucleos(t)ide analogues have been ineffective against HDV.

“So, over the past decade, there has been a quest for better therapies in delta hepatitis,” he said.

Koh and colleagues designed the phase 2a open label LIFT HDV study, which comprised 26 patients with HBV and chronic HDV including quantifiable HDV RNA in serum. Patients received lonafarnib (Merck, Sharp & Dohme) 50 mg with ritonavir (AbbVie) 100 mg orally twice daily, and Lambda (pegylated interferon lambda, Eiger Pharmaceuticals) 180 µg subcutaneously once a week.

At 12 weeks, median HDV RNA in 21 patients declined from baseline (3.36 vs. 4.74 log IU/mL; P < .0001). Five patients achieved undetectable HDV RNA and five patients achieved HDV RNA below the lower limit of quantification (BLOQ).

At the 24-week end of therapy, the HDV RNA decline in 16 patients declined further (3.18; P < .0001). Seven patients achieved undetectable HDV RNA and three patients achieved BLOQ.

Altogether, 18 patients achieved more than 2 log decline during 24 weeks of therapy.

Adverse events were mostly mild to moderate and included gastrointestinal-related side effects such as weight loss, hyperbilirubinemia, and anemia. Three patients had a dose reduction during the study and four patients discontinued.

Koh noted that per protocol discontinuation was mostly due to known side effects related to pegylated interferon lambda.

“By the end of therapy, 53% of subjects achieved below the limit of quantification or undetectable serum HDV RNA levels,” Koh concluded. “Viral load decline did not differ between those achieving more than 2 log decline vs. undetectable, suggesting that baseline viral load may serve as a predictor of response.”

Currently, all patients enrolled in the study have been dosed and are in various phases of treatment or post-treatment follow-up. – by Talitha Bennett

Reference: Koh C. Abstract LO8. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.

Disclosure: Koh reports no relevant financial disclosures.