- Acts against: HIV-1
- Formulation: Silicone matrix vaginal ring
- Active ingredient: Dapivirine
- Length of action: One month, with a three-month ring in development
- Status: One open-label extension study ongoing and one completed; first regulatory review underway
Why is the dapivirine ring important?
Existing prevention methods have not done enough to stop the spread of HIV among women. Pending regulatory approval, the monthly dapivirine ring would provide women with the first discreet, long-acting prevention option.
How does the dapivirine ring work?
The ring is made of a flexible silicone matrix polymer and contains the ARV dapivirine, an NNRTI, which is slowly released over the course of a month.
The ring delivers dapivirine directly at the site of potential infection, with low systemic absorption. Women insert the flexible, long-acting ring themselves into the vagina and replace it every month.
What is its development history?
IPM brought the dapivirine ring from concept to Phase III clinical trials in just seven years. In 2004, IPM embarked on an extensive program of preclinical assessments of dapivirine in various formulations. To provide discreet, long-acting protection to women, IPM prioritized a ring formulation in 2010. IPM collaborated with partners to develop and evaluate early prototypes, ultimately advancing Ring-004 to late-stage clinical trials.
What is its clinical history?
IPM conducted two Phase I and one Phase I/II safety trials of the ring from 2009 to 2012, all of which found the ring to be safe and well-tolerated. Given the ring’s promise, IPM then launched two Phase III studies in 2012: The Ring Study, led by IPM, and ASPIRE, led by IPM’s clinical trial partner, the US National Institutes of Health-funded Microbicide Trials Network (MTN). These two studies enrolled approximately 4,500 women in Malawi, South Africa, Uganda and Zimbabwe to assess the ring’s efficacy and long-term safety. A package of smaller safety trials was also conducted to collect the safety data required by global and national regulatory authorities to seek licensure for the ring’s public use.
Two open-label studies, DREAM and HOPE, launched in July 2016 to provide the ring to former Phase III trial participants for one year and to gain insights into how women will use the ring now that they know the ring was found to help reduce HIV risk in the Phase III studies. HOPE completed in October 2018 and DREAM is scheduled to complete in December 2018, with final results for both studies expected in 2019.
What does the research show so far?
Phase III studies: In February 2016, The Ring Study and ASPIRE announced that the monthly dapivirine ring developed by IPM helped reduce the risk of HIV-1 infection in women and was well-tolerated. Additional analyses indicate that higher efficacy is associated with increased ring use. Learn more about the Phase III results.
Open-label studies: Interim data from DREAM and HOPE announced in March 2018 found increases in product use and suggest greater HIV risk reduction, with final results expected in 2019. Learn more about the interim open-label study results.
What are the next steps for the dapivirine ring?
IPM is pursuing approvals from global and national regulatory authorities for the ring's use in countries where women face the highest risk for HIV. IPM is working with a global network of government, donor, private and civil society partners to determine how the ring could best fit into HIV prevention programs and prepare for the potential roll-out of the ring at an affordable cost, pending its approval.
Who is IPM currently partnering with to develop and test the ring?
- ARV licenses: Janssen Sciences Ireland UC
- Development: Queens University Belfast
- Manufacturing and raw materials: QPharma; Trelyst
- Clinical trials: Microbicide Trials Network