Agency is yet to rule on expanding Selzentry into this indication.
FDA’s advisory panel voted 10 to 4 in favor of Pfizer’s Selzentry for use in treatment-naïve adult patients with CCR5-tropic HIV-1 virus as part of combination therapy. It remains to be seen whether the drug will pass muster at the FDA as data showed that Selzentry (maraviroc) along with Combivir® was as effective as Sustiva® plus Combivir at reducing viral load.
Selzentry was granted accelerated approval in August 2007 and full approval in November 2008 by the FDA for use in treatment-experienced adult patients with only CCR5-tropic HIV-1 virus in combination with other antiretroviral therapies. The drug works by inhibiting viral entry into uninfected cells by blocking its predominant entry route, the CCR5 co-receptor.
Monogram Biosciences provides a companion diagnostic for Selzentry, called Trofile®. This assay identifies patients with CCR5-tropic HIV-1 virus.
FDA’s Antiviral Drugs Advisory Committee made its decision based on 48- and 96-week efficacy and safety data from an ongoing Phase III MERIT (maraviroc versus efavirenz regimens as initial therapy) trial and MERIT ES (analysis of the MERIT study with the enhanced sensitivity Trofile™ assay).
Results of MERIT at 48 weeks showed that Selzentry plus Combivir was as effective as Sustiva (efavirenz) plus Combivir at reducing viral load for the co-primary endpoint of less that 400 copies/mL. The combination, however, did not show noninferiority for the co-primary endpoint of less than 50 copies/mL at 48 weeks. Safety results at 96 weeks showed that among those patients who remained on therapy, less than half the number of malignancies were observed in patients taking Selzentry compared to those taking Sustiva.
MERIT ES is a retrospective analysis, which utilized Trofile in screening samples from the MERIT trial. Results of MERIT ES at 48 weeks showed that treatment-naïve patients with CCR5-tropic HIV-1 in the Selzentry combo arm experienced comparable virologic suppression to undetectable levels (< 50 copies/mL) as those in the Sustiva combo arm.