July 11, 2013

Simeprevir Shines in Hep C Trial

Gastroenterology and Endoscopy News

In the News

ISSUE: JULY 2013 | VOLUME: 64:7

by David Wild

Orlando, Fla.—Of patients who relapsed following treatment with peginterferon (PEG-IFN)-based therapy for chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, 80% experienced rapid and sustained virologic response with triple therapy including PEG-IFN-2a, ribavirin (RBV) and simeprevir, an experimental oral, once-daily HCV NS3/4A protease inhibitor (PI). Results from the Phase III PROMISE study were presented at the 2013 Digestive Disease Week meeting (abstract 869b).

The findings led Gregory Gores, MD, executive dean for research at Mayo Clinic, Rochester, Minn., to speculate that simeprevir will soon be added to the clinician’s HCV treatment toolbox.

“The surprising efficacy of simeprevir triple therapy in patients who had relapsed after prior RBV plus PEG-IFN therapy, and in patients with advanced liver fibrosis, along with its once-daily dosing, minimal drug–drug interactions and good safety profile, make it likely the drug will be approved by the FDA for use in HCV patients,” said Dr. Gores, who was not involved in the research.

Eric Lawitz, MD, professor of medicine at the University of Texas Health Science Center and vice president of scientific and research development at the Texas Liver Institute in San Antonio, and his colleagues randomized 260 patients with HCV GT1 to receive the triple therapy and 133 similar patients to receive an oral placebo with PEG-IFN/RBV, both for 12 weeks, in a double-blind fashion. Simeprevir recipients who experienced a drop in HCV RNA below 25 IU/mL after four weeks of treatment and who had undetectable HCV RNA at 12 weeks received an additional 12 weeks of PEG-IFN/RBV alone, whereas those who did not meet these criteria received an additional 36 weeks of PEG-IFN/RBV treatment, for a total of 48 weeks. All placebo recipients received 36 weeks of PEG-IFN/RBV after the initial 12 weeks of placebo plus PEG-IFN/RBV treatment.

Dr. Lawitz reported that 77% of patients who received simeprevir experienced a rapid virologic response (RVR), and 79% had a sustained virologic response 12 weeks after treatment completion (SVR12). In contrast, 3% of placebo recipients achieved RVR, and 37% achieved SVR12 (P<0.001 for simeprevir vs. placebo).

SVR12 rates among various patient subgroups were higher in the simeprevir arm compared with the placebo arm, Dr. Lawitz reported. These included patients with METAVIR scores of F0-F2 (82% vs. 41%), METAVIR scores of F3 (73% vs. 20%), METAVIR scores of F4 (74% vs. 26%), HCV GT1a (70% vs. 28%), HCV GT1b (86% vs. 43%), interleukin-28 B (IL28B) genotype CC (89% vs. 53%), IL28B genotype GT CT (78% vs. 33%) and IL28B genotype GT TT (65% vs. 19%; P<0.001 for all).

Only 7% of simeprevir recipients required 48 weeks of treatment, and rates of on-treatment failure and post-treatment relapse with the drug were 3% and 19%, respectively, compared with 27% and 48% with placebo.

There were no differences in serious adverse events in the simeprevir and placebo groups.

Dr. Lawitz said the study participants were a difficult-to-treat population and included those with prior treatment failure and compensated and fibrotic liver disease.

“Hepatitis C is a complex disease, and we need multiple treatment options in order to provide our patients with the best possible chance of successful therapy,” he concluded.


Dr. Lawitz has received research support from Abbott Laboratories, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Intercept Pharmaceuticals, Janssen Pharmaceuticals, Medtronic, Merck & Co., Novartis, Presidio, Roche, Santaris Pharmaceuticals, Scynexis and Vertex Pharmaceuticals. Dr. Gores has no conflicts of interest.

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