Drug & Device Development

HCV response to IFN/ribavirin hints at response to telaprevir

Last Updated: 2012-12-05 18:01:06 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - In a subset of patients with hepatitis C virus (HCV) who don't respond well to peginterferon/ribavirin therapy, their viral load at four weeks of treatment might hold some clues to how they'll respond to telaprevir.

That suggestion, in a November 26 online paper in the Journal of Hepatology, applies to patients who are "null responders" to peginterferon/ribavirin at four weeks, not to those who are relapsers or partial responders.

"This (information) is particularly helpful for patients who responded poorly to their first course of therapy when a lead-in approach to therapy may help them to choose whether or not to pursue a further course of treatment," lead author Dr. Graham R. Foster of Queen Mary's University of London told Reuters Health by email.

Dr. Foster and colleagues note in their paper that telaprevir and another antiviral, boceprevir, have recently been approved for use along with peginterferon/ribavirin.

There have been reports of viral resistance in patients who fail to respond to the new drugs, however, which may be particularly significant in prior null responders. Early identification of patients unlikely to respond to treatment (and likely to develop resistance) can leave future options open and reduce the costs and inconvenience of therapy that is likely to be futile, the investigators say.

To gain more information, they analyzed data from the REALIZE trial, which enrolled prior relapsers and partial responders as well as prior null responders. It included a 12-week telaprevir treatment arm with a four-week peginterferon alfa/ribavirin lead-in phase.

The current subanalysis was restricted to the 240 patients in this arm for whom data was available on response at four weeks.

At that point, a reduction in HCV RNA of at least 1 log10 was seen in 90% of relapsers, 60% of partial responders, and 41% of null responders.

Sustained virologic response on telaprevir in those who achieved or did not achieve such reduction was 94% vs 62% in relapsers, 59% vs 56% in partial responders, and 54% vs 15% in null responders.

In relapsers and partial responders, therefore, "there is no apparent benefit of assessing response after a peginterferon/ribavirin lead-in with the aim of guiding telaprevir-based treatment," the authors say.

In fact, they write, assessment at that point "may result in missed opportunities to cure prior relapsers and prior partial responders with telaprevir-based therapy."

But for patients known to be prior null responders, "on-treatment response after a four-week peginterferon/ribavirin lead-in may provide clinically useful prognostic information."

The REALIZE trial was funded by Janssen Pharmaceuticals and Vertex Pharmaceuticals, which employ four of the paper's 15 authors and have financial relationships with others.

SOURCE: http://bit.ly/VxhCUb

J Hepatol 2012.