- Acts against: HIV-1
- Delivery method: Silicone matrix vaginal ring
- Active ingredient: Dapivirine, an antiretroviral drug
- Length of action: One month, with a three-month ring in development
- Regulatory status: Received positive opinion from European Medicines Agency, WHO recommendation and WHO prequalification; country regulatory submissions on rolling basis in Africa; under review in the US
- Research status: Open-label studies underway among adolescents & young women, pregnant and breastfeeding women
Why is the dapivirine ring important?
Existing prevention methods have not done enough to stop the spread of HIV among women, who bear a disproportionate burden of the epidemic, particularly in sub-Saharan Africa. 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.
How effective is the ring?
Phase III studies: Two Phase III studies found that the monthly dapivirine ring reduced the risk of HIV-1 infection in women and was well-tolerated with long-term use. The Ring Study, led by IPM, found that the ring reduced overall risk by 35%, and ASPIRE, conducted by the US National Institutes of Health-funded Microbicide Trials Network (MTN), found that the ring reduced overall risk by 27%.
Open-label studies: Final results from DREAM and HOPE, the open-label extension trials (OLEs) that enrolled former participants of The Ring Study and ASPIRE, respectively, showed increases in ring use and modeling data suggest greater risk reduction—by over 50% across both studies—compared to the Phase IIIs. Although these modeling results are limited due to the lack of a placebo comparison group, they indicate an encouraging trend we hope to see continue if the ring is approved and rolled out.
What is the ring's status and what are the next steps?
The ring received a positive scientific opinion from the European Medicines Agency in July 2020 for its use among women ages 18 and older in developing countries. In November 2020, the ring received WHO prequalification, a designation that confirms that the product meets global standards for quality, safety and efficacy, and will help guide national and global procurement decisions, pending country regulatory approvals for its use. The WHO also issued a recommendation for the dapivirine ring in January 2021 as an additional prevention choice for women at substantial risk of HIV infection.
Through the WHO’s collaborative registration procedure, in Q4 2020, IPM began submitting the first phase of applications to countries in eastern and southern Africa where HIV incidence among women remains high. IPM is seeking regulatory approvals in Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda, Zambia and Zimbabwe, and will seek to make the product available in Eswatini and Lesotho through national import license processes. We hope to submit to other countries in Africa in the future. IPM also submitted an application to the US Food and Drug Administration in December 2020. 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 rollout of the ring at an affordable cost, pending its approval.
Research with key groups: A set of studies is designed to help us understand how the ring can work for women at different times in their lives: when they are under age 18, and when they are pregnant or breastfeeding. Research is planned among women ages 18-25 to better understand the ring’s efficacy among this high-risk group and to collect additional data on safety and potential resistance. In addition, the REACH study, led by MTN, is underway in Africa to assess the ring’s safety and adherence among young women 16-21. Safety studies in Africa are also ongoing among pregnant women (DELIVER) and breastfeeding women (B-PROTECTED), both conducted by MTN..
Follow-on products: In addition, the monthly ring is a platform technology for longer-acting products that could further expand women’s options, such as a dapivirine ring that could be used for three months, and rings that have broader appeal, such as IPM’s three-month dapivirine-contraceptive ring designed to prevent both HIV and unintended pregnancy.
What is the dapivirine ring’s potential impact?
Modeling studies show that microbicides like the dapivirine ring would have a meaningful public health impact as part of a comprehensive HIV prevention portfolio and could avert infections that would not be prevented by another method.
If approved, the dapivirine ring would offer the first woman-controlled, long-acting HIV prevention method and could be an important new option for women, who bear the greatest burden of the global HIV/AIDS epidemic.
Who are IPM's research and manufacturing partners?
- ARV license: Janssen Sciences Ireland Unlimited Company
- Development: Queens University Belfast
- Manufacturing and raw materials: Sever Pharma Solutions (formerly QPharma); Omnichem; Nusil
- Clinical trials: US National Institutes of Health-funded Microbicide Trials Network and research center partners in Africa
What is the ring's 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 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 nearly 4,600 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.
When the Phase III studies found the ring to help reduce HIV risk in 2016, two open-label studies, DREAM and HOPE, launched in July of that year to provide the ring to former Phase III trial participants for one year and to gain insights into how women use the product. HOPE completed in October 2018 and DREAM completed in January 2019, with final results for both announced in 2019.
- Open-label extension study results:
- Pooled Phase III trial results (July 2017): IAS 2017 abstract and presentation
- Primary Phase III trial results (Feb. 2016):