By Walter Alexander, Contributing Writer, MedPage Today
Published: April 01, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Adding telaprevir, an investigational oral protease inhibitor, to peginterferon alfa-2a and ribavirin substantially increased sustained response rates in patients with genotype 1 hepatitis C virus (HCV) infection who had previously failed the standard therapy, a researcher said here.
Results from the phase III REALIZE trial indicated that, among prior relapsers, sustained response rates with two telaprevir-containing regimens were 83% and 88%, compared with 24% for peginterferon alfa-2a and ribavirin plus placebo (both P<0.001), reported Stefan Zeuzem, MD, of Johann Wolfgang Goethe University Medical Center in Frankfurt am Main, Germany.
Lower sustained viral response rates were seen in patients who previously showed partial or no response to the two standard drugs, but they were still significantly better than in the placebo group (41% in both telaprevir arms versus 9% in the control group, P<0.001).
Zeuzem presented the findings here at the European Association for the Study of the Liver (EASL) annual meeting.
"T plus P plus R was superior to P plus R alone in treatment-experienced populations including prior relapsers, partial responders, and null responders," he told attendees.
The findings confirm those of earlier studies, including one reported last year in the New England Journal of Medicine.
The current standard of care for HCV is the combination of peginterferon alfa-2a and ribavirin, Zeuzem explained, but it fails to achieved sustained viral responses in 60% of patients with HCV genotype 1.
REALIZE assigned 662 patients to three treatment arms in a 2:2:1 ratio:
• T12/PR48: Telaprevir, peginterferon, and ribavirin for 12 weeks followed by placebo plus peginterferon and ribavirin for four weeks and then the two standard drugs alone for 32 weeks
• LIT12/PR48: Placebo plus peginterferon and ribavirin for four weeks, followed by telaprevir and the standard drugs for 12 weeks, and then the standard drugs alone for 32 weeks
• Pbo/PR48: 48 weeks of peginterferon plus ribavirin, with placebo for the first 16 weeks
The REALIZE primary endpoint was the proportion of these patients achieving sustained viral responses, defined as undetectable plasma HCV RNA at 24 weeks after the last planned intake of study medication. Whether the four-week lead-in with standard therapy alone made a difference in responses was a secondary objective.
Telaprevir was given at 750 mg every eight hours. Standard doses of the other drugs were used (180 mcg/week for peginterferon, 1,000 to 1,200 mg/day for ribavirin).
Null responders, partial responders, and relapsers to previous peginterferon plus ribavirin constituted about 28%, 19%, and 54%, respectively, of the cohort. Nearly half of patients were in advanced stages of disease; 89% had a baseline HCV viral load of >800,000 IU/mL. Median age was about 51 and more than two-thirds were men.
Sustained viral responses were seen in 83% of the T12/PR48 group and 88% of the LIT12/PR48 patients versus 24% of the Pbo/PR48 group.
These results, Zeuzem pointed out, indicated that the four-week lead-in with standard therapy did not improve response rates compared with including telaprevir from the outset.
Responses rates of 41% were seen in the previous null or partial responders in both the T12/PR48 and LIT12/PR48 groups, compared with just 9% of the previously unresponsive Pbo/PR48 patients.
Zeuzem said that sustained response rates were higher for prior partial responders than for prior null responders.
Relapse rates were 10% each for the two telaprevir-containing arms and 23% for the Pbo/PR48 arm.
Among the most common adverse events during any treatment phase, fatigue occurred in 55% of the T12/PR48 patients, 50% of the LIT12/PR48 group, and 40% of the Pbo/PR48 group. Frequencies of pruritus were similar.
Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28%, 22%, and 8% of the T12/PR48, LIT12/PR48, and Pbo/PR48 groups, respectively.
For each of these adverse events, and for anemia, rash, nausea and diarrhea, the incidence was more than 10% greater in the T12/PR48 arm than in the Pbo/PR48 arm.
Discontinuations of any study drug during telaprevir treatment occurred in 29% of patients. Rash and anemia were the most common adverse effects associated with drug stoppage.
"These are really exciting results for this particularly difficult-to-treat group of patients," commented Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of the EASL.
"Over 60% achieved an SVR. Compared with patients who previously relapsed after P-plus-R treatment, those who are partial responders did less well, and the null group was disappointing, but that was not entirely surprising."
A marketing application for telaprevir has been filed with the FDA, which is giving it priority review. The agency's deadline for a decision is May 23.
Zeuzem disclosed relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex.
Thursz declared he had no relevant industry relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Zeuzem S, et al "REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response or relapse to peginterferon/ribavirin" EASL 2011; Abstract 192.
Source
No comments:
Post a Comment