Thursday, November 15, 2012

AASLD - Peginterferon lambda-1a decreases viral load more quickly, safely than alfa-2a in HCV patients

Peginterferon lambda-1a decreases viral load more quickly, safely than alfa-2a in HCV patients

November 14, 2012
BOSTON — Noncirrhotic patients with chronic HCV experienced a more rapid decrease in HCV RNA and fewer side effects when treated with pegylated interferon lambda-1a compared with alfa-2a in a study presented at The Liver Meeting.

In phase 2b of the EMERGE trial, researchers administered ribavirin and 120 mcg peginterferon lambda-1a, 180mcg peginterferon lambda-1a or 240 mcg peginterferon lambda-1a or 180 mcg peginterferon alfa-2a for up to 48 weeks to 407 noncirrhotic, treatment-naive patients with chronic HCV. They included 384 patients with genotype 1 and 23 patients with genotype 4. Ninety-eight patients received 120 mcg, 102 received 180 mcg, 104 received 240 mcg of lambda, and 103 patients received alfa. The impact of lambda on HCV RNA levels was evaluated, along with safety, through 72 weeks.

Approximately 60% of patients completed treatment and follow-up for each group. Treatment response, defined as undetectable RNA levels, occurred as follows:

  • After 4 weeks of treatment (RVR): 6.1% of 120 mcg lambda group; 14.7%, 180 mcg lambda; 16.3%, 240 mcg lambda; 5.8%, alfa.
  • After 12 weeks (cEVR): 55.1%, 120 mcg lambda; 55.9%, 180 mcg lambda; 56.7%, 240 mcg lambda; 36.9%, alfa.
  • After 48 weeks (ETR): 58.2%, 120 mcg lambda; 57.8%, 180 mcg lambda; 55.8%, 240 mcg lambda; 56.3%, alfa.
  • After 72 weeks (SVR24): 45.9%, 120 mcg lambda group; 37.3%, 180 mcg lambda; 39.4%, 240 mcg lambda; 36.9%, alfa.
Investigators noted that treatment with lambda led to a more rapid decrease in HCV RNA than treatment with alfa. Incidence of viral breakthrough and relapse were similar among all four groups. Of the three evaluated lambda doses, 180 mcg was selected for use in phase 3 of the study. Patients in the 240 mcg group experienced hepatic laboratory abnormalities and were reduced to a 180-mcg dose during the trial.

Among patients receiving 180 mcg lambda, incidence of serious adverse events were fewer (2.9% compared with 6.8% in the alfa group), as were incidence of interferon dose reductions (7.8% vs. 28.2%), reduction or withholding of ribavirin (10.8% of patients compared with 33.0%), and flu-like (12.7% vs. 45.6%) and musculoskeletal symptoms (15.7% vs. 46.6%). Patients receiving lambda had fewer increases to ALT and more incidence of direct bilirubin greater than 1.2 mg/dL, and were less likely to experience abnormal hemoglobin levels, low neutrophils and low platelet counts than alfa-treated patients.

“At the 180-mcg dose selected for phase 3, lambda was associated with rapid reduction of viral load, with significantly higher RVR and eVR rates, similar SVR24 rates and low relapse rates following end of treatment,” researcher Andrew J. Muir, MD, MHS, Duke University Medical Center, said. “The improved tolerability, together with the faster time to virologic response, supports the further assessment of lambda … in patients chronically infected with genotypes 1 and 4.”
Disclosure: The researchers report numerous financial disclosures.

For more information:
Muir AJ. P214: Peginterferon Lambda-1a (Lambda) Compared to Peginterferon Alfa-2a (Alfa) in Treatment-Naïve Patients with HCV Genotypes (GT) 1 or 4: SVR24 Results From EMERGE Phase 2b. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.

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