1. Do the safety and efficacy data presented support accelerated
approval of maraviroc for treatment-experienced HIV-1 infected patients
with CCR5-tropic virus?
If not, please discuss what additional data are needed to provide
sufficient evidence of efficacy and safety.
If so, please comment on additional data (e.g., patient subgroups,
longer term follow-up, etc.) that Pfizer should provide post-marketing
to further characterize the safety and efficacy profile of maraviroc
2. There have been several safety concerns during the development of all
CCR5 co-receptor antagonists, including risk of lymphomas and infection,
hepatotoxicity, and tropism switching. Please discuss each of these
issues with respect to maraviroc specifically, and provide
recommendations for possible product labeling, post-marketing studies or
post-marketing risk management strategies.
4. The Monogram Trofile assay was used to screen subjects for
enrollment and to monitor subjects for tropism switching. Please
discuss how you would recommend assays for tropism testing be used for
the management of subjects who might receive maraviroc in clinical
Please discuss the impact of the availability of maraviroc on the
design of future Phase 3 trials for new antiretroviral agents in the
treatment-experienced population and provide recommendations for how
those trials should be designed accordingly.