Reuters Health Information (2010-05-05): Telaprevir improves sustained response rates in refractory HCV
Drug & Device Development
Telaprevir improves sustained response rates in refractory HCV
Last Updated: 2010-05-05 17:03:13 -0400 (Reuters Health)
NEW YORK (Reuters Health) - In patients with refractory genotype 1 hepatitis C virus (HCV), adding telaprevir to peg-interferon and ribavirin significantly increases rapid and sustained viral response rates, researchers announced at Digestive Disease Week 2010.
"There are literally hundreds of thousands of patients that fit that description in the U.S.," presenter Dr. Andrew J. Muir told Reuters Health. "Genotype 1 HCV is the most common genotype in the U.S. and it has the lowest response rate to standard therapy."
He said that in previous trials, treatment-naive patients showed excellent responses to telaprevir -- an antiviral protease inhibitor -- in combination with peg-interferon alfa-2a and ribavirin.
The two phase II trials presented this week in New Orleans both involved patients who did not have a sustained virologic response to peg-interferon and ribavirin.
In the PROVE3 trial, Dr. Muir and his colleagues randomized 342 patients to one of three arms:
-- 12 weeks of telaprevir 750 mg three times daily plus 24 weeks of peg-interferon and ribavirin at standard doses (T12/PR24);
-- 24 weeks of telaprevir plus 48 weeks of peg-interferon and ribavirin (T24/PR48); or
-- peg-interferon and ribavirin for 48 weeks (PR48), the control arm.
Rapid and sustained virologic response rates were substantially higher in the two telaprevir arms compared with the control arm. For example, for patients with HCV RNA at least 800,000 IU/mL at baseline, sustained response rates were 50% (53/106) in T12/PR24, 52% (54/104) in T24/PR48, and 10% (10/104) for PR48.
"Most risk groups do quite well," Dr. Muir said. Results were similar in subset analyses (e.g., age over 50, black race, obesity, male gender, cirrhotics).
On multivariate analysis, the following were positive predictors of sustained virologic response: treatment (p < 0.001), baseline HCV RNA level < 800,000 (p = 0.017), and prior response (p < 0.001).
The second trial, Study 107, was an open-label rollover study of triple therapy among control patients in the PROVE 1/2/3 trials. Treatment response was greater among relapsers than among non-responders.
After 12 weeks of telaprevir and 24 weeks of peg-interferon and ribavirin (n = 80), the rate of sustained virologic response was highest in patients who had relapsed during the initial phase II trial (92%, 23/25) and those with a prior viral breakthrough (86%, 6/7). Prior partial responders (defined as at least a 2-log decrease at week 12, detectable virus at week 24) were next, at 60% (15/25).
Among prior non-responders, only 3 of 23 patients (13%) had a sustained response by 24 weeks. However, when treatment with peg-interferon and ribavirin was extended to 48 weeks, 57% (16/28) had a sustained response.
If these "very encouraging results" are replicated in ongoing phase III trials, Dr. Muir hopes that telaprevir will gain regulatory approval in 2011.