The addition of mericitabine to a pegylated interferon and ribavirin regimen for patients with chronic HCV safely improved treatment efficacy in a recent study.
In a phase 2b, multicenter, double blind trial, researchers randomly assigned treatment-naive patients with chronic HCV genotype 1 or 4 to receive either 1,000 mg mericitabine (Genentech) (n=81) or placebo (n=85) twice daily for 24 weeks, in addition to a 48-week regimen of pegylated interferon alfa-2a and ribavirin. Treated patients who achieved extended rapid virologic response (eRVR, defined as HCV RNA levels below 15 IU/mL between weeks 4 and 22) discontinued therapy after 24 weeks, while remaining patients completed the peginterferon/ribavirin regimen.
Paul J. Pockros
“Most believe that nucleoside polymerase inhibitors [NPI] will be the backbone of antiviral therapies for HCV,” researcher Paul J. Pockros, MD, director of the Liver Disease Center and the SC Liver Research Consortium at Scripps Clinic in La Jolla, Calif., told Healio.com. “The first NPI was R1626 (balapiravir), [which] proved to be potent, but toxic. Therefore, the critical need was to develop a safe NPI.”
Throughout treatment and follow-up, treated patients had higher rates of virologic response than placebo recipients. eRVR occurred in 60.5% of mericitabine recipients and 12.9% of placebo patients, while 56.8% of treated patients achieved sustained virologic response (SVR) vs. 36.5% of placebo recipients. Higher SVR rates among mericitabine recipients persisted after subdivision for IL28B genotype (77.8% vs. 56% among CC genotypes; 44.1% vs. 16.2% for non-CC genotypes) and cirrhosis (38.1% vs. 21.7% among cirrhotic patients; 63.3% vs. 41.9% among noncirrhotic patients). Relapse occurred in 27.7% of treated and 32% of placebo patients.
Adverse events, including fatigue, headache and nausea, occurred similarly for treated and placebo patients. Treated patients experienced more serious adverse events (6.2% vs. 3.5%), although fewer were forced to discontinue treatment for safety-related reasons.
“A 24-week response-guided combination regimen of mericitabine 1,000 mg BID plus Peg-IFN-a2a/RBV is well tolerated and more effective than a standard 48-week course of Peg-IFN-a2a/RBV,” Pockros said. “However, it is not as potent as sofosbuvir, the competing NPI currently in phase 3 development.”
Disclosure: See the study for a full list of relevant disclosures.