Microbicide Trials Network

MTN Studies Update and FDA Panel Recommendation

Dear MTN Friends and Family,

We thought that this would be a good time to update you all on the status of the VOICE study, ASPIRE and MTN-017, as well as share our reflections on the recommendation by the Antiviral Drugs Advisory Committee that the U.S. Food and Drug Administration (FDA) approve Truvada for use as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV transmission.

First, an update on the VOICE study. The final follow-up visits are slated to occur in August. We hope to complete data cleanup and analysis in time for publication and presentation of the data in the first quarter of 2013. As you know, VOICE was designed to determine the safety and effectiveness of daily use of oral tenofovir, oral Truvada and tenofovir gel. All women randomized to oral tenofovir and tenofovir gel have discontinued study product following the recommendation by the DSMB that neither product was any better than its matched placebo in protecting against HIV among the women in those study groups. Critically, VOICE is continuing to evaluate oral Truvada as PrEP, and will provide crucial information about the use of this product in women – information that will be highly relevant to the FDA’s decision and broader discussions, as we explain below.

What’s coming after VOICE? ASPIRE, a Phase III study of the dapivirine vaginal ring, remains on schedule to begin enrollment in August or September. The first site trainings are scheduled to take place during June in Cape Town and Kampala. We hope that by the end of September, all sites will have been trained. We are especially excited about this study and our collaboration with the International Partnership for Microbicides (IPM). IPM is the ring’s developer and regulatory sponsor and is also conducting The Ring Study (IPM 027) in parallel with ASPIRE.

We are also pleased to report that MTN-017, the first expanded safety study of a rectal microbicide, received a favorable review by the DAIDS Prevention Sciences Review Committee and we anticipate having version 1.0 ready by mid-July, and, thereafter, to begin implementation. Specifically, MTN-017 is evaluating the reduced glycerin formulation of tenofvir gel as well as oral Truvada in an open-label cross-over design, similar to MTN-001. Needless to say, the study will provide critical data that will not only help to advance the rectal microbicide research agenda, but also data important to better understanding the safety and pharmacokinetics of Truvada in MSM.

What effect will possible FDA approval of Truvada have, and how will VOICE, in particular, contribute to the evolving evidence base about PrEP in women? A great deal of discussion during the FDA Advisory Committee’s meeting last week focused on the evidence for Truvada in men who have sex with men. There was general agreement, reflected in the final voting results and the discussion, that despite the outstanding data on efficacy of Truvada in women in the Partners PrEP study, more data are needed to address challenges of adherence and real-world implementation in women, such as those represented in the VOICE Study. Moreover, while the FDA decision will be critical to stimulating inclusion of PrEP as part of a broader prevention strategy, it’s very likely that many regulatory and scientific entities outside of the U.S.—particularly in Africa—will strongly consider the VOICE results as they move forward with enhanced prevention efforts in the coming years.

We will need to consider the potential impact of the FDA’s decision on all of our studies, and to do so in consultation with our communities, our funders and other stakeholders. The FDA panel’s recommendation to approve Truvada was a momentous occasion for all of us in the HIV prevention field. The panel heard several hours of presentations and public testimony centered primarily on iPrEx and the Partners PrEP Study, the two pivotal trials that were the basis of Gilead Sciences’ supplemental drug application. We are immensely proud of our friend and colleague Bob Grant, who led iPrEx, and MTN’s own Connie Celum and Jared Baeten, who led Partners PrEP, as well as John Mellors, who presented to the FDA on behalf of Gilead. We want to congratulate both study teams, but especially Gilead and the studies’ sponsors, the National Institute of Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation, for believing in and supporting this research. The FDA’s decision whether to approve Truvada as oral PrEP is expected before June 15.

In short, this is a time of great pride and excitement. But we still need more options. Truvada is not a magic bullet – and even with approval, there’s still much more we need to understand about its safety and efficacy, especially in women; and there’s more work to be done to ensure we have not just the one intervention, but multiple tools. For our part, we need to conduct trials of only the highest quality, because the men and women throughout the globe who are at risk of HIV are counting on us to do so.

Sincerely,
 

Sharon Hillier

Ian McGowan