SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

Faldaprevir regimen is effective as first treatment for HCV genotype 1