Clinical

Interferon-free HCV regimens on the horizon?

Last Updated: 2013-08-16 13:50:10 -0400 (Reuters Health)

By Megan Brooks

NEW YORK (Reuters Health) - Among patients with HCV genotype 1 infection, more than half had a sustained virologic response 12 weeks after completing an interferon-free regimen consisting of faldaprevir with deleobuvir plus ribavirin.

Interferon is tough to tolerate and many patients discontinue it or have contraindications to it. Interferon-free regimens would be a major advance in the treatment of chronic HCV, Dr. Stefan Zeuzem, Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany and colleagues say.

In the previously reported phase 1b SOUND-C1 study, they found that the combination of faldaprevir, a protease inhibitor, and deleobuvir (formerly BI207127), a nonnucleoside polymerase inhibitor, with ribavirin for four weeks showed rapid and strong activity against HCV genotype 1 and did not cause serious or severe adverse events.

Results of the phase 2b SOUND-C2 study, published in the New England Journal of Medicine August 15, build on this earlier trial by assessing the efficacy and safety of the interferon-free combination of faldaprevir plus deleobuvir, with or without ribavirin, for 16, 28, or 40 weeks.

The study involved 362 previously untreated patients with HCV-1 infection. They were randomized to faldaprevir 120 mg once daily and deleobuvir 600 mg three times daily plus ribavirin for 16, 28, or 40 weeks (TID16W, TID28W, or TID40W, respectively); faldaprevir 120 mg once daily and deleobuvir 600 mg twice daily plus ribavirin for 28 weeks (BID28W); or faldaprevir 120 mg once daily and deleobuvir 600 mg three times daily, without ribavirin, for 28 weeks (TID28W-NR).

The researchers say 52% to 69% of patients on these interferon-free regimens had a sustained virologic response 12 weeks after the completion of therapy.

This primary end point was met by 59% of patients in the TID16W group and the TID28W group, 52% of patients in the TID40W group, 69% of patients in the BID28W group, and 39% of patients in the TID28W-NR group.

There was no difference in achieving the primary endpoint according to treatment duration or dosage among ribavirin-containing regimens, the researchers say. They note that the response was significantly higher with TID28W than with TID28W-NR (p=0.03).

Rates of a sustained virologic response 12 weeks after the completion of therapy were 56% to 85% in patients with genotype 1b infection compared with 11% to 47% in those with genotype 1a infection, and 58% to 84% in those with IL28B CC versus 33% to 64% with non-CC genotypes.

Rash, photosensitivity, nausea, vomiting, and diarrhea were the most common adverse events.

A phase 3 study is underway (http://1.usa.gov/14BL7D0).

HCV genotype 1 is the most prevalent genotype in many parts of the world and it's hard to cure. In an email to Reuters Health, Dr. Zeuzem said he thinks "multiple interferon-free regimens could be approved, with various options for patients and physicians."

This might also fuel price competition, maybe leading to lower prices, which is "particularly important for countries with high HCV burden and restricted health care budgets," he added.

The SOUND-C2 trial was funded by Boehringer Ingelheim. A complete list of author disclosures is available with the full text of the article on NEJM.org.

SOURCE: http://bit.ly/1eGYoQ4

N Engl J Med 2013;369:630-639.