Results from the REALIZE study show that combination treatment with telaprevir is superior to standard treatment for patients with hepatitis C virus infection.
Results from the REALIZE study indicate that combination treatment with telaprevir is superior to standard treatment for patients with hepatitis C virus infection.
Adding telaprevir, an investigational oral protease inhibitor recently recommended for approval by an FDA advisory panel, to pegylated-interferon alfa-2a (P) and ribavirin (R) (P/R) substantially increases rates of the sustained viral responses (SVRs) considered to represent cure for hepatitis C virus (HCV) infection. In approximately 60% of patients with genotype 1 chronic HCV infection, said Paul Pockros, MD, Scripps Research Institute, La Jolla, CA, combination treatment fails with R/B, the current standard of care.
Pockros presented SVR findings from the REALIZE trial, a Phase 3 evaluation of telaprevir in 662 patients whose responses to prior P/R had been null or partial, or who relapsed after initial response. The REALIZE primary objective was to evaluate the proportion of these patients achieving SVR, defined as undetectable plasma HCV RNA at 24 weeks after the last planned intake of study medication. A secondary objective was evaluation of the effect of a 4-week P/R lead-in on efficacy in one of the trial’s three study arms.
Patients in the international, multicenter, double-blind, placebo-controlled trial were randomized 2:2:1, to one of two telaprevir-containing regimens or to one P/R+placebo group. The telaprevir-containing regimens included 12 weeks of telaprevir (750 mg q8h) + P (180 µg/w) + R (1000-1200 mg/d), one with the 4-week P/R+placebo lead-in (LI12/PR48), and one followed by 4 weeks of P/R+placebo (telaprevir 12/PR48). Both were followed by P/R in weeks 16-48. Patients in the third arm (Pbo/PR48) received P/R+placebo for 16 weeks followed by P/R in weeks 16-48. Follow-up continued for all arms until SVR assessment at week 72.
Null responders, partial responders and relapsers constituted 27%/18%/and 55%, respectively, of the cohort, and nearly 50% of patients were in advanced stages of disease. Median age was ~51 years (~70% males).
The SVR rates among prior relapsers were 83% for telaprevir 12/PR48 (p<0.001 vs. placebo/PR48P), 88% for LIT12/PR48 (p<0.001 vs. placebo/PR48P) and 24% for placebo/PR48. Among prior non-responders (partial or null responders), SVR rates were 41% for both telaprevir arms (p<0.001 vs. placebo/PR48P) and 9% for placebo/PR48. Looking at the non-responders more closely, Pockros pointed out that SVR rates were higher for prior partial responders than for prior null responders. He said further that the use of the 4-week lead-in phase with P+R led to no reductions in virologic failure or relapse rates and no improvements in SVR rates.
Relapse rates were 10% each for the two telaprevir-containing arms and 23% for the placebo/PR48 arm.
During treatment phases, the most common adverse events were fatigue, pruritus and anorectal symptoms. Fatigue occurred in 55% (T12/PR48), 50% (LIT12/PR46) and 40% (placebo/PR48), and pruritus in 52% (T12/PR48), 50% (LIT12/PR46) and 427% (placebo/PR48). Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28% (T12/PR48), 22% (LIT12/PR46) and 8% (placebo/PR48). For each of these adverse events, and for anemia, rash, nausea and diarrhea, incidence was >10% greater in the T12/PR48 arm than in the placebo/PR48 arm. Discontinuations of any study drug during T treatment occurred in 29% of patients, and were most common for rash (5% (T12/PR48), 4% (LIT12/PR46) and 0% (placebo/PR48), and anemia 2% (T12/PR48), 3% (LIT12/PR46) and 0% (placebo/PR48).
Commenting on the adverse events with telaprevir in a DDW press conference, REALIZE co-investigator Zobair. M. Younossi, MD, vice president of Inova Health System, Falls Church, VA, said, “Generally speaking, these safety rates are consistent with previously reported data.”
Pockros concluded, “Telaprevir with P/R was superior to P/R alone in treatment-experienced populations including prior relapsers, partial responders, and null responders.”