You have reached the HIVandHepatitis.com legacy site. Please visit our new site at hivandhepatitis.com

 HIV and Hepatitis.com Coverage of the
18th Conference on Retroviruses and
Opportunistic
Infections (CROI 2011)
 February 27 - March 2, 2011, Boston, MA
HCV Protease Inhibitor Boceprevir Improves Response for Treatment-Naive and Non-responders

SUMMARY: Merck's investigational hepatitis C virus (HCV) protease inhibitor boceprevir improved sustained response rates when combined with pegylated interferon plus ribavirin in both previously untreated patients and those who were non-responders or relapsers after prior therapy, according to 2 Phase 3 studies presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston.

By Liz Highleyman

Mark Sulkowski
(Photo: Liz Highleyman)

The advent of direct-acting antiviral agents that interfere with various steps of the HCV lifecycle will usher in a new era of treatment for chronic hepatitis C. The current standard-of-care, pegylated interferon (Pegasys or PegIntron) plus ribavirin, leads to sustained virological response (SVR), or a cure, less than half the time for individuals with hard-to-treat HCV genotype 1.

The first such drugs -- boceprevir and Vertex's HCV protease inhibitor telaprevir -- are expected to be approved this year. Initially, they will be used in combination with standard-of-case therapy, but all-oral regimens without interferon are currently being studied.

At CROI, researchers presented final data from 2 pivotal Phase 3 studies of telaprevir: SPRINT-2, which enrolled previously untreated patients, and RESPOND-2, which enrolled prior non-responders and relapsers. These results were previously presented at the American Association for the Study of Liver Diseases (AASLD) meeting this past fall.

SPRINT-2 and RESPOND-2 did not include people with HIV -- making these presentations unusual for CROI -- but HIV specialists recognize the need to get up to speed on hepatitis C treatment, since many HIV positive people are coinfected with HCV. As recently reported, the conference also featured the first data on telaprevir for HIV/HCV coinfected individuals.

SPRINT-2

SPRINT-2 included 1097 treatment-naive HCV genotype 1 patients (about 60% men). Participants were divided into cohorts according to race, as people of African descent do not respond as well to interferon-based therapy. One cohort included 159 black patients, while the other included 938 people of other racial/ethnic groups ("non-black"). Most had high HCV viral load and nearly 10% had advanced liver fibrosis.

All participants started a regimen of 1.5 mcg/kg/week pegylated interferon alfa-2b (PegIntron) plus 600-1400 mg/day weight-adjusted ribavirin for a 4-week lead-in period. After this, they were randomly assigned to continue on pegylated interferon/ribavirin, either alone or in combination with 800 mg boceprevir 3-times-daily.

Boceprevir recipients were further allocated to receive either the triple combination for a fixed duration of 48 total weeks or response-guided therapy. In the latter arm, all participants stopped boceprevir at week 28. Those with undetectable HCV RNA during weeks 8-24 stopped all drugs, while those with continued detectable HCV viral load stayed on pegylated interferon/ribavirin through week 48.

Results

In an intent-to-treat analysis, SVR rates were significantly higher in the boceprevir arms -- 66% with fixed-duration treatment and 63% with response-guided therapy -- compared with the standard therapy arm (38%).
In all arms, white patients had higher response rates than blacks: 68% vs 53% in the fixed duration boceprevir arm, 67% vs 42% in the response-guided therapy arm, and 40% vs 23% in the standard therapy arm.
The relapse rate was 9% in both boceprevir arms, compared with 22% in the standard therapy group.
Almost all boceprevir recipients with undetectable HCV RNA during weeks 8-24 achieved SVR: 96% with fixed-duration boceprevir, 97% with response-guided therapy.
Among boceprevir participants who had detectable HCV viral load at least once during weeks 8-24, still 74% achieved SVR in both arms.
The most common treatment-related adverse events across arms were fatigue, headache, and nausea.
Anemia and dysgeusia (odd taste sensations) were more common in the boceprevir groups than in the standard therapy group.
Rates of discontinuation due to adverse events, however, were similar across arms: 16% in the standard therapy arm, 16% in the boceprevir fixed-duration arm, and 12% in the response-guided therapy arm.

Based on these findings, the researchers concluded that a regimen of boceprevir plus pegylated interferon/ribavirin "significantly increased SVR" compared with standard therapy alone, and HCV RNA at week 8 could be used to determine duration of pegylated interferon/ribavirin.

RESPOND-2

RESPOND-2 enrolled 400 treatment-experienced genotype 1 patients, both prior non-responders and relapsers (undetectable at the end of treatment followed by viral rebound). About two-thirds were men, 12% were black, and 12% had liver cirrhosis.

Again, all participants initially received pegylated interferon/ribavirin standard therapy for a 4-week lead-in period. They were then randomly assigned to continue on pegylated interferon/ribavirin either alone or in combination with 800 mg 3-times-daily boceprevir.

Boceprevir recipients were assigned to either stay on triple therapy through week 48 or use response-guided therapy. In the latter group, participants stopped boceprevir at week 36; those with undetectable HCV RNA at week 8 stopped all treatment, while those with detectable viral load continued on pegylated interferon/ribavirin through week 48.

Results

In an intent-to-treat analysis, patients in the boceprevir arms had significantly higher SVR rates -- 67% with fixed-duration therapy and 59% with response-guided therapy -- than those in the standard therapy arm (21%).
People with undetectable HCV RNA at week 8 had high SVR rates in all arms: 88% with fixed-duration boceprevir, 86% with response-guided boceprevir, and 100% with standard therapy.
People taking boceprevir, however, were about 6 times more likely to have undetectable HCV RNA at week 8 (46%-52% vs 9%).
In all arms, previous relapsers had higher SVR rates than prior non-responders: 75% vs 52% with fixed-duration boceprevir, 40% vs 69% with response-guided boceprevir, and 29% vs 7% with standard therapy.
Here too, the most common adverse events were fatigue, headache, and nausea.
Anemia occurred about twice as often in the boceprevir arms: 46% with fixed-duration boceprevir, 43% with response-guided boceprevir, and 20% with standard therapy.
Serious adverse events likewise occurred about twice as often in the boceprevir arms: 14%, 10%, and 5%, respectively.

The investigators concluded that boceprevir added to pegylated interferon/ribavirin "significantly increased SVR."

They added that boceprevir could be used to treat patients with all types of interferon non-responsiveness, and that fixed-duration and response-guided therapy were "equally effective."
Investigator affiliations:

Abstract 115: John Hopkins Univ School of Medicine, Baltimore, MD; Cedars-Sinai Med Ctr, Los Angeles, CA; Gastroenterology/Hepatology/Certified Endoscopy Ctrs, Alexandria, VA; St Louis Univ School of Medicine, St Louis, MO; AO Fatebenefratelli e Oftalmico, Milan, Italy; Hannover Medical School, Hannover, Germany; Ctr for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY; Univ of Pennsylvania, Philadelphia, PA; Merck, Whitehouse Station, NJ; Ctr Hosp Univ de Nancy, Univ Henri Poincaré Nancy 1, Vandoeuvre-lès-Nancy, France.

Abstract 116: Henry Ford Hosp, Detroit, MI; St Louis Univ School of Medicine, St Louis, MO; Alamo Medical Research, San Antonio, TX; Univ Paris, Hosp Beaujon, Clichy, France; Baylor College of Medicine, Houston, TX; Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; Cedars-Sinai Med Ctr, Los Angeles, CA; Merck, Whitehouse Station, NJ; Hosp Univ Vall d'Hebrón, Barcelona, Spain.

3/15/11

References

M Sulkowski, F Poordad, J McCone, et al. BOC Combined with P/R for Treatment-naive Patients with HCV Genotype-1: SPRINT-2 Final Results. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 115.

S Gordon, B Bacon, E Lawitz, et al. HCV RESPOND-2 Final Results: High Sustained Virologic Response among Genotype-1 Previous Non-responders and Relapsers to pegIFN/RBV when Re-treated with BOC + PEGINTRON/RBV
18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 116.





 


 

 


 



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



    Google Custom Search