Berlin—A novel variant of pegylated interferon (PegIFN) called PegIFN-lambda is significantly more effective than PegIFN-alfa-2a (Pegasys, Genentech) at suppressing viral loads in patients with certain genotypes of hepatitis C virus (HCV), according to preliminary findings from an ongoing randomized trial. Patients also experienced fewer adverse events on the novel PegIFN.

“If the superior virological response rates and minimal adverse events are sustained through the completion of this study and replicated in other research, this form of interferon will represent a major advance in the treatment of chronic hepatitis C,” said Emmet Keeffe, MD, professor emeritus of medicine, Stanford University Medical Center, Palo Alto, Calif., who was not involved in the study.

An estimated 20% of patients stop treatment for HCV because of side effects associated with PegIFN-alfa-2a. PegIFN-lambda attaches to fewer cellular receptors than PegIFN-alpha-2a and thus may be a safer and equally effective alternative.

In this study, lead researcher Stefan Zeuzem, MD, and colleagues at 39 international centers randomly assigned individuals with chronic HCV to receive ribavirin in combination with PegIFN-alfa-2a 180 mcg (n=132), PegIFN-lambda 120 mcg (n=130), PegIFN-lambda 180 mcg (n=131) or PegIFN-lambda 240 mcg (n=133). The study is ongoing, but the current efficacy and safety findings are based on 12 weeks of double-blinded treatment.

The data showed that 14.7% and 16.5% of those with HCV genotypes 1 and 4 who received 180 and 240 mcg of PegIFN-lambda, respectively, experienced a rapid virologic response (RVR) to the novel drug compared with 5.8% of patients with the same HCV genotypes who took PegIFN-alfa-2a (P<0.05). The RVR rate among individuals with genotypes 1 and 4 who received 120 mcg of PegIFN-lambda was 6%.

Complete early virologic response rates were 55%, 55.9% and 56.3% among those with HCV genotypes 1 and 4 who received 120, 180 and 240 mcg of PegIFN-lambda compared with 37.9% among PegIFN-alfa-2a recipients (P<0.05). Response rates among those with HCV genotypes 2 and 3 did not differ significantly between the treatment groups, the researchers reported.

Patients administered PegIFN-lambda also experienced fewer flu-like and musculoskeletal symptoms as well as fewer cytopenias (Table). However, aspartate and alanine transaminase levels rose to more than five times the upper limit of normal in 17.4% of those receiving the highest dose of PegIFN-lambda, and direct bilirubin concentration exceeded 1.2 mg/dL in 7.6% of patients in the same group. These adverse events resolved with dose reduction or drug discontinuation.

Table. Adverse Events in Patients Receiving PegIFN-lambdaa For Hepatitis C Virus Infection
PegIFN-alfa-2a 180 mcg (n=132)PegIFN-lambda 240 mcg (n=133)PegIFN-lambda 180 mcg (n=131)PegIFN-lambda 120 mcg (n=130)
Flu-like symptoms42.9%9.7%9.9%12.5%
Musculoskeletal symptoms46.6%14.2%14.5%18%
Hemoglobin <10 g/dL44%12.9%15.4%20.5%
Neutrophils <750/mm315.2%–0.8%–
Platelets <50,000/mm314.4%– ––
PegIFN, pegylated interferon a All patients also received ribavirin.

“This is indeed a promising new drug,” said Dr. Zeuzem, professor and chair, Department of Medicine, Johann-Wolfgang Goethe University Hospital, Frankfurt/Main, Germany, who presented his group’s findings at the 46th annual meeting of the European Association for the Study of the Liver (Abstract 1360).

“Now we need to assess longer-term sustained virological responses and to accumulate more safety data,” he said.

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