First CCR5-Antagonist Approved for Use in Treatment-Naive Setting Provides Additional Treatment Option

20 November 2009 --Today, ViiV Healthcare announced that the U.S. Food and Drug Administration (FDA) has approved the expanded use of Selzentry (maraviroc) tablets, in combination with other antiretroviral agents, to include adult patients with CCR5-tropic HIV-1 virus who are starting treatment for the first time (treatment-naive).

Selzentry works by blocking HIV from binding to CCR5 sites on human cells. HIV can use other sites to bind to and enter cells. Clinical data shows that for patients who have not taken antiretrovirals before, the vast majority carry HIV that only binds to CCR5.

"The use of Selzentry in those untreated with antiretrovirals is a natural progression as patients in this population are more likely to have virus that enters cells by binding to CCR5 sites," said Dr. John Pottage, Chief Scientific and Medical Officer of ViiV Healthcare. "ViiV Healthcare is committed to continuing efforts to expand the current indications for Selzentry to include appropriate treatment-naive populations throughout the world."

Selzentry, in combination with other antiretroviral agents, is indicated for adult patients infected with only CCR5-tropic HIV-1. This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of Selzentry in treatment-experienced subjects and one study in treatment-naive subjects. Both studies in treatment-experienced subjects were conducted in clinically advanced, 3-class antiretroviral experienced (NRTI, NNRTI, PI, or enfuvirtide) adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The following points should be considered when initiating therapy with Selzentry: (1) Adult patients infected with only CCR5-tropic HIV-1 should use Selzentry; (2) Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for Selzentry use. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on Selzentry; (3) Use of Selzentry is not recommended in subjects with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a phase 2 study of this patient group; (4) The safety and efficacy of Selzentry have not been established in pediatric patients; and (5) In treatment-naive subjects, more subjects treated with Selzentry experienced virologic failure and developed lamivudine resistance compared to efavirenz.

This action is in response to the review of the supplemental New Drug Application (sNDA) submitted to the FDA by Pfizer Inc, and is based on 48- and 96-week efficacy and safety data from the ongoing Phase 3 MERIT (Maraviroc versus Efavirenz Regimens as Initial Therapy) study and MERIT ES (re-analysis of the MERIT study, assay which utilized the enhanced sensitivity Trofile assay in screening samples from the MERIT study).

Results of MERIT ES at 96-weeks showed that treatment-naive patients with CCR5-tropic HIV-1 virus taking Selzentry plus zidovudine/lamivudine experienced comparable virologic suppression to undetectable levels (<50 copies/mL) compared to those taking efavirenz plus zidovudine/lamivudine (183/311 and 190/303, respectively). The median increase from baseline in CD4+ cell counts at week 96 was 184 cells/mm3 for the Selzentry arm compared to 155 cells/mm3 for the efavirenz arm. Patients were screened into the study using the original Trofile assay which is no longer available.

In the MERIT analysis at 96 weeks, the overall number of patients who failed to respond to therapy was similar in both arms. There was a greater number of virologic failures in the arm containing Selzentry and a greater number of discontinuations due to adverse events in the arm containing efavirenz.

MERIT Safety results at 96-weeks also showed that among those patients who remained on therapy, less than half the number of malignancies were observed in patients taking Selzentry (4/360) compared to those taking efavirenz (10/361) . While no increase in malignancy has been observed with Selzentry, due to this drug's mechanism of action it could affect immune surveillance and lead to an increased risk of malignancy. No new safety signals were identified in association with Selzentry at 96-weeks.

Overall, the most frequently reported adverse events seen with Selzentry in both treatment-experienced and treatment-naïve patients were colds, cough, fever, rash, gastrointestinal side effects including gas and bloating, and dizziness.

"The availability of maraviroc for appropriate HIV patients starting therapy is an important advancement in HIV/AIDS care," said Dr. Michael Saag, Professor of Medicine and Director of the Center for AIDS Research at the University of Alabama at Birmingham. "With rates of new HIV infection continuing to rise in the U.S., enhancing existing regimens with newer effective treatments that are generally well tolerated is critical."

See the full press release or the Selzentry prescribing information for complete safety information and warnings.

Selzentry is currently approved for use in treatment-experienced adult patients with CCR5-tropic HIV-1 virus as part of a combination therapy in several markets around the world including the U.S., Canada, Japan, and the European Union.

Maraviroc is marketed under the trade name Selzentry in the U.S. and Celsentri in all other countries in which it is approved.

For more information on ViiV Healthcare, its management, portfolio, pipeline, and commitment, please visit www.viivhealthcare.com.