FDA to Fast Track 1% Tenofovir (Press Release)

Press Release from CONRAD

October 25, 2010, Arlington, VA - - The U.S. Food and Drug Administration (FDA) held an end-of-Phase II meeting to determine the next steps required for U.S. licensure of 1% tenofovir gel, a microbicide product recently found to be effective at  reducing the rate of HIV and herpes infection in women when used before and after sex.

The meeting, held on October 20, 2010, was requested by CONRAD, a division of the Eastern Virginia Medical School in Norfolk, VA. CONRAD was one of the partners in the Phase II study, “CAPRISA 004,” which evaluated 1% tenofovir gel in prevention of male-to-female HIV transmission in 889 women in South Africa. USAID provided funding for the trial, conducted by the Centre for Programme Research for AIDS in South Africa and U.S. based FHI, which was the first study to show that a vaginal gel can reduce the risk of HIV and herpes infection in women. CONRAD manufactured and provided the tenofovir gel for the study.

Tenofovir gel was found to be 39% effective in reducing a woman’s risk of becoming infected with HIV during sex and 51% effective in preventing genital herpes infections in the women participating in the trial. Results of the CAPRISA 004 clinical trial were reported in July 2010 and represent the first “proof of concept” for a vaginal microbicide.

A number of key stakeholders contributed to the collaborative meeting with the FDA, including representatives from the U.S. National Institutes of Health, the U.S. Agency for International Development, Gilead Sciences, Microbicides Trial Network (MTN), South African clinical investigators, the International Partnership for Microbicides (IPM) and FHI.

During the meeting, the FDA stated their preference for two well-controlled studies to verify the safety and efficacy of 1% tenofovir gel prior to submission of a New Drug Application (NDA). The FDA furthermore stated that the NIH-sponsored Phase IIB study, MTN-003, known as VOICE (Vaginal and Oral Interventions to Control the Epidemic), represents a second adequate and well-controlled study that would, if successful, serve as the second pivotal trial together with CAPRISA 004 to support the submission of an NDA for 1% tenofovir gel.

In addition, the FDA has granted Fast Track approval designation for 1% tenofovir gel, which facilitates the development and expedites the review of drugs that are intended for treating serious diseases and fill an unmet medical need. With Fast Track designation, an NDA can be submitted as a “rolling review”, which allows a clinical trial sponsor to submit completed sections of its NDA for review by the FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed.

The agency agreed that the current preclinical program for 1% tenofovir gel is sufficient to support a future NDA. However, they stated that additional safety data on adolescents would be needed and that information on in vivo drug interaction studies with commonly used vaginal products should be obtained. Also, the FDA will ultimately need data on post menopausal women. It was also agreed that a future meeting with the FDA would be held to address any outstanding discussions associated with product quality, including chemistry, manufacturing and controls (CMC). Since much of the clinical work on 1% tenofovir gel has been and will be conducted in South Africa, FDA officials indicated that they can work through the FDA’s “Office of International Programs” with the goal of coordinating the data and review processes with the South African Medicines Control Council.

CONRAD and its partners appreciate the contributions and detailed recommendations put forth by the FDA, which have helped clarify the next steps required for testing and licensure of 1% tenofovir gel.

In 2006, CONRAD and IPM obtained a co-exclusive, royalty-free license from Gilead Sciences to develop 1% tenofovir gel as a topical microbicide for use by women in developing countries to prevent HIV.

Straight Talk with Dr Zeda Rosenberg, CEO of the International Partnership for Microbicides

Via PlusNews Global

There were cheers and some tears at the International AIDS Conference in Vienna in July when delegates heard the news that a clinical trial in South Africa, had found a vaginal gel containing the antiretroviral drug, tenofovir, was 39 percent effective at reducing women's risk of contracting HIV during sex.

"There were tears from many people – tears of happiness that finally there is something we can work towards - and a lot of tears of sadness for all of the women whose lives have been lost waiting for a microbicide," Dr Zeda Rosenberg recalled at a recent meeting in Johannesburg, South Africa, hosted by the International Partnership for Microbicides (IPM), a non-profit organization.

IPM is involved in coordinating and funding the long process of developing effective microbicides - products that women can apply vaginally to protect themselves against HIV - and making sure they reach the women in developing countries who most need them. Rosenberg, who has been working in the field of HIV prevention research for more than two decades and is CEO of IPM, talked to IRIN/PlusNews after the meeting.

QUESTION: What do you think is the likelihood that women will use a microbicide any more consistently than men use condoms?

ANSWER: Part of the issue with condoms is that although they're highly effective, many people put a large value on skin-to-skin contact and ... in long-term relationships it just seems that condoms aren't used as often because it's a trust issue, an issue of intimacy; and also, if everyone uses a condom all the time, women can't get pregnant.

So there really does need to be a method that women can use where they and their partners don't feel it reduces intimacy, allows for conception, and is culturally acceptable.

I think microbicides need to be marketed with the message: 'Condoms should be used', because you don't want a less effective microbicide replacing highly effective condoms. At some point there will be all of these partially effective methods that, when used together, will be highly effective.

Adherence was a challenge in the [South African] trial - those women who reported greater adherence had greater efficacy. [The investigators] also saw a drop-off in product use over the course of the study, which means you need something that's sustainable in the long term.

For more click here.