NEW YORK (Reuters Health) - Simeprevir plus peginterferon and ribavirin is noninferior to telaprevir plus peginterferon and ribavirin for treating previous null or partial responders with chronic hepatitis C virus (HCV) genotype 1 infection, according to Janssen's ATTAIN trial.
"The drug regimen in developing countries currently includes peginterferon, ribavirin, and telaprevir," Dr. K. Rajender Reddy from University of Pennsylvania in Philadelphia told Reuters Health by email. "In the U.S. and other countries where access to the latest research and treatment for HCV are available, physicians have moved towards all oral therapy and away from interferon-based therapy such as these, as they are known to come with a significant number of side effects and not as effective."
Dr. Reddy and colleagues from 169 investigational sites in 24 countries sought to demonstrate the noninferiority of simeprevir 150 mg once a day (379 patients) versus telaprevir 750 mg three times a day (384 patients), each in combination with peginterferon alfa-2a and ribavirin. Patients had chronic HCV genotype 1 infection and compensated liver disease and were null or partial responders to previous peginterferon alfa and ribavirin treatment.
"The ATTAIN study is the first head-to-head comparison of two direct-acting antivirals for the treatment of chronic HCV infection," the researchers note.
Endpoints included sustained virological response at 12 weeks (SVR12, the primary endpoint), rapid virological response (at week 4), on-treatment failure, viral breakthrough (a subgroup of on-treatment failures) and viral relapse.
More patients completed treatment with simeprevir (87%) than with telaprevir (80%), largely due to differences in discontinuations as a result of adverse events, the researchers report in The Lancet Infectious Diseases, online December 5.
The overall SVR12 rate was 54% in the simeprevir group and 55% in the telaprevir group (p=0.007 for noninferiority), and the rates for simeprevir were noninferior to those for telaprevir in both previous partial responders and previous null responders.
The groups did not differ significantly in the proportions of patients achieving rapid virological responses, viral breakthrough or relapse.
During the first 12 weeks of treatment, 69% of simeprevir patients and 86% of telaprevir patients experienced adverse events deemed at least possibly related to study drug, and more telaprevir patients (8%) than simeprevir patients (2%) discontinued their drug because of adverse events.
"We expected the tolerability to be better with simeprevir and it appeared to be the case," said Dr. Reddy, who has been an adviser to Jannsen and other drugmakers.
"The observations from the study present simeprevir, pegylated interferon, and ribavirin as a good therapeutic option for regions of the world where all oral therapies are unavailable or cost prohibitive," Dr. Reddy concluded.
"Will 48 weeks of interferon-based treatment be the standard of care in low-income and middle-income countries for previous interferon nonresponders in the face of higher response rates that can be achieved with more expensive treatments?," asks Dr. Geoffrey Dusheiko from UCL Institute of Liver and Digestive Health and Royal Free Hospital in London, UK, in a related commentary. "Will cheaper but less effective interferon-based treatments be used first, reserving more expensive treatments for those who fail treatment? Such a two-tiered policy would seem to be intrinsically inadvisable, and efforts to harmonize access to highly effective interferon-free regimens for treatment experienced patients should intensify."
"Simeprevir in combination with peginterferon and ribavirin is a safer but not more efficacious regimen than telaprevir for partial and null responders," he concluded. "The drug's real promise lies in its use in effective and safe combination direct-acting antiviral regimens. It is time to cut the cord to long-duration treatments with interferon."
Telaprevir was withdrawn from the U.S. market in October 2014.
"These regimens would be relevant only in areas where combinations of oral agents are not available, since avoidance of interferon is highly desirable," Dr. Raymond T. Chung from Massachusetts General Hospital in Boston said of the treatments used in the study.
"In those areas where only simeprevir or telaprevir are available, simeprevir may be advantageous in view of its once daily dosing and improved tolerability profile," Dr. Chung, who was not involved in the trial, told Reuters Health by email.
"We can expect to see continued refinement and improvement of DAA (direct antiviral agent) classes, such as protease inhibitors, and our ability to successfully treat HCV with high rates of cure, and with increasingly well-tolerated regimens, will evolve rapidly," he concluded.
Janssen funded the trial, employed eight of the 17 authors, and had various relationships with all but two of the other authors, as well as with Dr. Dusheiko.
SOURCE: http://bit.ly/1BP90wc and http://bit.ly/1uNbNi6
Lancet Infect Dis 2014.
Reuters Health Information © 2014
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