VIENNA – A new, once-daily, single-pill regimen for treating chronic hepatitis C infection without interferon or ribavirin showed 95% eradication efficacy after 12 weeks of safe treatment in a pivotal trial with 421 treatment-naive patients.
The study results also showed that the combination of grazoprevir and elbasvir, drugs that target two different hepatitis C proteins, was equally effective in noncirrhotic and compensated cirrhotic patents. Although more than 90% of the enrolled patients were infected by genotype 1 hepatitis C, the new combination also showed efficacy in the small number of patients enrolled who were infected by either genotype 4 or genotype 6 virus.
Perhaps the most important consequence of the new study, the C-EDGE trial, is that it put the grazoprevir-elbasvir combination on track for near-term approval as another simple, effective, interferon- and ribavirin-free regimen to cure patients of chronic hepatitis C infection, a step that would sharpen competition in this niche and could lead to price reductions among the currently available, high-cost treatments.
“I love competition,” said Dr. Stefan Zeuzem as he reported the results at the meeting, which was sponsored by the European Association for the Study of the Liver. “We should have many regimens that produce excellent sustained virologic response because we see in the data that certain drug combinations fit better for special indications,” said Dr. Zeuzem, professor and chief of medicine at J.W. Goethe University Hospital in Frankfurt, Germany.
“This provides an excellent option, and we need more options” for treating chronic hepatitis C, said Dr. K. Rajender Reddy, a coauthor with Dr. Zeuzem on the study and professor and director of hepatology at the University of Pennsylvania in Philadelphia.
“It’s one pill, it works in more than 90% of patients, the side effect profile is good,” and the grazoprevir-elbasvir combination can be used in patients with severe renal impairment and a glomerular filtration rate below 30 mL/min per 1.73 m2, something not recommended with one of the major drugs now available for treating hepatitis C, sofosbuvir (Sovaldi and Harvoni), Dr. Reddy said in an interview.
And it’s a “huge step” toward simpler hepatitis C–treatment regimens that are applicable to a broader range of patients, commented Dr. Donald M. Jensen, a hepatologist in Oak Park, Ill. who helped develop hepatitis C–treatment recommendations for the American Association for the Study of Liver Diseases.
“It offers the ability to treat multiple genotypes and had a high success rate, but it still relies on a protease inhibitor so it will still have issues of drug-drug interactions,” Dr. Jensen said in an interview. “Hopefully, as more regimens come out, companies will have to price their regimens competitively.”
The C-EDGE trial randomized 316 patients to immediate treatment with the grazoprevir-elbasvir combination and 105 patients to 4 weeks of placebo treatment as controls for adverse-effect monitoring, after which they also began active treatment. The trial enrolled patients during June 2014-March 2015 at 60 centers in nine countries. The rate of sustained virologic response after 12 weeks, the study’s primary endpoint, occurred in 92% of patients infected with genotype 1a, 99% of those infected by 1b, 100% of the 18 patients infected by genotype 4, and in 8 of the 10 patients infected by genotype 6, Dr. Zeuzem reported.
Concurrent with his talk at the meeting on April 24, the results were published online (Ann. Int. Med. 2015 [doi:10.7326/M15-0785]).
“You can use this regimen comfortably for genotype 4. Whether you want to take the data seriously for genotype 6 is a question,” noted Dr. Reddy, who acknowledged that the 10-patient experience for genotype 6 is too preliminary to provide firm guidance on efficacy. The apparent efficacy of the grazoprevir-elbasvir combination beyond genotype 1 reflects the fact that both drugs are “second generation” agents, particularly designed to have pan-genotype efficacy, Dr. Reddy said.
The safety profile of the two drugs was encouraging, with adverse events occurring at rates no different than in the placebo arm. No patient had a serious adverse event on active treatment, and two patients in the active arm discontinued because of an adverse event.
The data also showed that the regimen was effective regardless of age, sex, race, or the presence of compensated cirrhosis. All of the virologic failures occurred in patients with high viral loads – greater than 800,000 IU/mL – when they started treatment, a finding consistent with prior reports, Dr. Zeuzem said. The patients who had virologic failure carried resistance-associated variant strains of hepatitis C.