Genotype 1b HCV Patients Fare Better on Boceprevir

(Article from Medscape on IAS presentation culling data from the SPRINT-2 and RESPOND-2 trails that find that genotype 1a patients have a lower barrier to resistance than genotype 1b. This was also found to be true for Telaprevir as well)

Genotype 1b HCV Patients Fare Better on Boceprevir
Emma Hitt, PhD

July 22, 2011 (Rome, Italy) — Boceprevir/peginterferon plus ribavirin is associated with a small but consistently higher sustained viral response (SVR) rate and a lower rate of development of boceprevir-related resistance-associated variants (RAVs) in patients infected with hepatitis C virus (HCV) genotype 1b subtype than in those infected with genotype 1a subtype, according to new data from the SPRINT-2 and RESPOND-2 phase 3 trials.

Daria Hazuda, PhD, vice president of virus and cell biology at Merck Research Laboratories, in Whitehouse Station, New Jersey, presented the findings in a late-breaking oral session here at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

"It was important to do this study in order to better understand the development of resistance with boceprevir," Dr. Hazuda told Medscape Medical News. "Additional analyses of our clinical studies with boceprevir are ongoing. A 3.5-year long-term follow-up study is underway to evaluate the persistence of resistance-associated variants over time," she added.


Dr. Daria Hazuda
In the SPRINT-2 and RESPOND-2 clinical trials, Dr. Hazuda and colleagues compared the SVR to boceprevir in combination with pegylated-interferon alfa-2b plus ribavirin and the associated presence or absence of RAVs between patients with HCV genotype 1a and those with genotype 1b.

The rate of SVR among those receiving boceprevir in the 2 trials was higher in patients with genotype 1b than in those with genotype 1a (66%–73% vs 59%–64%). The number of patients with RAVs detected was higher in genotype 1a patients than in genotype 1b patients in SPRINT-2 (58% vs 48%) and in RESPOND-2 (48% vs 41%).

The researchers also found that the RAVs V36M and R155K were more common in genotype 1a patients, whereas T54A/S, A156S, and V170A were more common in genotype 1b patients.

RAVs were more common in patients with a poor interferon response (defined as a decline in viral load of less than 1 log at week 4) than in those with a good interferon response (a decline in viral load of 1 log or more at week 4) (68% vs 31%). Overall, baseline samples showed a low rate of RAVs, and most patients with RAVs still achieved SVR.

"Understanding which mutations develop and how long they persist may help us assess the potential for retreatment with first-generation protease inhibitors and, importantly, facilitate the development of next-generation protease inhibitors that can work effectively against resistant mutants," Dr. Hazuda explained.

According to Dr. Hazuda, the resistance variants observed with boceprevir are similar, if not identical, to those observed with telaprevir. "Although we do not know if retreatment will be possible, there should be no difference between these 2 first-generation protease inhibitors," she said.

Dr. Hazuda added that it is still not known how long these resistant variants last, or whether the viral population has been altered in a way to make it less likely that patients will respond to retreatment with another first-generation protease inhibitor.

"These are valuable phase 3 trial data, which emphasize the fact that the main determinant of the SVR is not the preexistence of RAVs at baseline but the response to interferon and ribavirin," said independent commentator Jean-Michel Pawlotsky, MD, professor of medicine at the University of Paris-Est, director of the Department of Virology at the Henri Mondor University Hospital in Créteil, France, and director of the Department of Molecular Virology and Immunology at the Mondor Institute of Biomedical Research.

"Patients and doctors should not be afraid of resistance to protease inhibitors," he told Medscape Medical News. "Hepatitis remains theoretically curable in 100% of cases, and new drugs will allow patients who failed on triple-combination therapy the opportunity for treatment in the future," he added.

The study was funded Merck and Co. Dr. Hazuda is an employee of Merck. Dr. Pawlotsky reports acting as a consultant to Vertex, Jannsen, Merck, and Roche.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract WELBX04. Presented July 20, 2011.

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