Arlington, Va. CONRAD Head of drug delivery, Meredith Clark, PhD, today presented preclinical data on a new intravaginal ring that provides contraception as well as HIV-1 and HSV-2 prevention at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition in San Antonio, Texas. This multipurpose prevention technology (MPT) can remain in the vagina for up to 90 days and releases the contraceptive levonorgestrel (LNG) and tenofovir (TFV), an antiretroviral that inhibits HIV and HSV replication in susceptible cells.
The CONRAD product development team, in collaboration with Dr. Patrick Kiser at Northwestern University, performed in vitro release testing and 3-month pharmacokinetic (PK) studies of the ring in rabbits and sheep, and compared drug levels to those seen with use of tenofovir gel. The PK studies found that levels of tenofovir in the target tissue delivered from the ring are similar or higher than those obtained after TFV 1% gel application, a product that has proven to be effective in preventing HIV and HSV infections in women. In addition, release of the contraceptive agent was also consistent with previous levels tested to be efficacious in women. Stability studies will continue and lead to Phase I clinical trials in women in 2014, which will test the combination ring, as well as a tenofovir-only ring.
Tenofovir is the first microbicide proven to be efficacious in humans, with the CAPRISA 004 clinical trial showing that women using the gel before and after sex reduced their risk of HIV infection by 39-54%. CAPRISA 004 also showed the gel to be 51% effective in reducing the transmission of HSV-2, making this combination ring potentially triple protective.
"The TFV/LNG ring is the first device to be tested in women that will offer contraception as well as HIV and herpes prevention," said Dr. Clark. "And so far, tenofovir is the only microbicide that has been proven to be effective in reducing HIV infections when used topically. It's important to develop a variety of delivery mechanisms for tenofovir in order to serve different women's needs."
CONRAD's product development director David Friend Ph.D added, "Products only work when they are used. By having a ring that can remain in the body for up to 90 days, our hope is that this ring will offer a solution to increase adherence, and therefore provide greater protection against HIV while also preventing pregnancy."
CONRAD's deputy director of clinical research, Marianne Callahan, will also present information on MPTs later this week at the International Conference on Family Planning in Addis Ababa, Ethiopia. The CONRAD sponsored panel, "Development of Multipurpose Prevention Technologies (MPTs): Pathway from Product Development to the End Users," will discuss how the development of MPTs are tied to the regulatory approval process, the importance of acceptability research within target populations, and the importance of taking a "systems approach" when considering feasibility of future introduction of a new technology.
In addition to the TFV/LNG intravaginal ring, CONRAD is testing the one-size-fits-most SILCS diaphragm with tenofovir gel. Used together, the diaphragm plus the gel can offer contraception plus the potential to reduce HIV and HSV-2 infections as an on-demand system providing immediate protection.
According to the World Health Organization, there are 35.3 million people living with HIV around the world and approximately 87 million unintended pregnancies occur each year. Ms. Callahan says, "An unintended pregnancy is more tangible than an invisible virus so MPTs may lead to increased product use by offering a crucial combination of protection that can have a major impact in developing countries."
|Contact: Annette Larkin|