Development of IPM's Vaginal Ring Designed to Reduce HIV-1 Receives $25 Million Boost

The United States Agency for International Development recently announced that it will award the International Partnership for Microbicides (IPM) up to $25 million for a period of 5 years to accelerate the potential rollout of its monthly vaginal ring designed to reduce the risk of HIV in HIV-negative women.

Made of a flexible silicone material, the ring contains dapivirine, a non-nucleoside reverse transcriptase inhibitor that blocks HIV’s ability to replicate inside of a healthy cell.

“This would be the first new product for women for the prevention of HIV,” Sharon Hillier PhD, principal investigator of the Microbicide Trials Network (MTN), director of reproductive infectious disease research in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine, said in a press release.

The award supports ongoing research of the ring including further study of former participants in ASPIRE and The Ring Study. It follows previous USAID awards, bringing IPM’s backing from the organization to $91 million.

The ring releases dapivirine over the course of 1 month, offering a discreet and long-acting HIV prevention method for women, who insert and replace the ring themselves. IPM will also be able to accelerate the development of a 3-month dapivirine ring offering women greater convenience, as well as reducing the product’s annual cost.

In July, IPM submitted the product for review to the European Medicines Agency. The application was based on the results of The Ring Study and ASPIRE, 2 independent, placebo-controlled phase 3 clinical trials assessing the ring’s long-term safety and efficacy in more than 4500 women in Malawi, South Africa, Uganda, and Zimbabwe. Data from 35 supporting clinical studies were also included.

The studies showed that the ring reduced women’s risk of acquiring HIV by about 30% overall—27% in ASPIRE and 31% in The Ring Study, respectively. Higher levels of protection were seen in women 21 and older who used the ring more regularly. (The studies included women ages 18 to 45.)

A more recent study, MTN-023/IPM 030, found that the dapivirine ring was also safe and effective in adolescent women. MTN-023/IPM 030 enrolled 96 girls ages 15—17 at 6 US sites: 2 affiliated with the MTN, University of Pittsburg, and the University of Alabama at Birmingham, and 4 affiliated with the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), St. Jude Children’s Research Hospital Memphis, The Fenway Institute in Boston, Children’s Hospital at Montefiore Medical Center, Bronx, and University of Colorado Denver School of Medicine.

The phase 2a clinical trial was conducted from July 2014 to July 2016, as ASPIRE and The Ring Study were underway.

Seventy-three participants were assigned to the dapivirine ring and 23 to a placebo ring, that looked and felt the same but contained no active drug, for 1 month at a time for a period of 6 months.

The results showed that there were no differences in safety outcomes between the 2 rings. Adherence to the ring was high, and a majority of patients (93%) stated they liked the ring.

A second trial called REACH will be launched by MTN later this year. The trial will collect safety data on the use of the ring in adolescent girls and young women in Africa, who are among the most vulnerable population at risk of acquiring HIV. For this trial, investigators will collect information on the safety of both the monthly ring and the oral Truvada tablet as daily pre-exposure prophylaxis (PrEP), and explore biological or physiological factors that can affect product efficacy or HIV susceptibility in adolescent girls or young women.

REACH, or MTN-034/IPM 045, will evaluate how adolescent girls and young women use the ring and the oral tablet, as well as preferences for the approaches in an open-label study.

Approximately 300 females aged 16—21 will be enrolled at 5 MTN-affiliated sites in Kenya, South Africa, Uganda, and Zimbabwe. They will be randomly assigned to use 1 of the products (either the dapivirine ring or oral tablet) for 6 months, and then will be switched to the product they were not assigned to originally, for another 6 months. After experiencing both approaches to PrEP, participants will have a choice to use the ring, the oral tablet, or neither, for an additional 6 months.

The study, expected to start late 2017 pending ethics committee and in-country approvals, is anticipated to take 3 years to complete.

IPM plans to submit new drug applications for the dapivirine ring to the South African Health Products Regulatory Authority in late 2017, the US Food and Drug Administration in 2018, and regulatory authorities in African countries. If approved, it would be the first biomedical prevention product exclusively for women.