Dapivirine Vaginal Ring Next Steps:
Study Results Review, Planning for
Introduction & Access, Regulatory Overview
Reported by Jules Levin
HIV Research for Prevention (HIVR4P), October 21-25, 2018, Madrid
slide talks below
Satellite Session: Planning for Success: Next Steps for Dapivirine Ring
Introduction and Objectives for the Session
Research and Modeling Update: Research & Regulatory Update
Planning for Introduction: Preparing for Introduction: What do we need to understand about the ring market?
J&J Global Public Health
see slides below following this press release from MTN
First clinical trial of new dapivirine ring with both anti-HIV drug and contraceptive
announcement from MTN - Microbicide Trials Network
Results have paved the way for a second study of the dual-purpose ring
for protecting against both HIV and unintended pregnancy
MADRID, 24 October, 2018 - In the first clinical study of a vaginal ring that releases the antiretroviral drug dapivirine as well as a contraceptive hormone, there were no safety concerns and the ring was well-tolerated, researchers from the National Institutes of Health-funded Microbicide Trials Network (MTN) reported today at the HIV Research for Prevention conference (HIVR4P 2018) in Madrid.
The ring is designed to provide protection against both HIV infection and unintended pregnancy for 90 days at a time. As this was the first clinical study of the dual-purpose ring, women used it for just 14-days so that researchers could assess its safety and measure how dapivirine and levonorgestrel, a synthetic progestin used in many contraceptives, are each taken up in the body. The ring contains 200 mg of dapivirine and 320 mg of levonorgestrel.
Given the encouraging results of the study, known as MTN-030/IPM 041, the research team has already launched a second Phase I trial of the dual-purpose ring in which participants will use it for 90 days.
Results of the current study found plasma concentrations of levonorgestrel throughout the 14-day period were at levels consistent with those required for contraception. As expected, the amount of dapivirine in plasma was comparatively higher with the dual-purpose ring than has been seen in previous clinical trials of a monthly ring containing 25 mg of dapivirine.
The 25 mg monthly dapivirine ring was found to be well-tolerated and to reduce HIV risk in two Phase III trials - ASPIRE, conducted by the MTN, and The Ring Study, conducted by the nonprofit International Partnership for Microbicides (IPM), which also developed the monthly ring and is seeking its regulatory approval. IPM developed the dual-purpose ring as well.
If approved, the monthly dapivirine ring would be the first biomedical HIV prevention method developed specifically for women. Researchers recognize that a ring that is replaced every three months may be easier for women to use than a monthly ring. And depending on individual and life circumstances, some women may find a product that can also double as their contraceptive method especially appealing.
"We are very encouraged by our findings in this first-in-human study of the dapivirine-levonorgestrel ring. And with a second study under way, we are another step closer to potentially having an easy-to-use product that can provide safe and effective, long-acting protection against both HIV and unintended pregnancy," said Sharon L. Achilles, M.D., Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, director of the Magee-Womens Research Institute Center for Family Planning Research and protocol chair of the MTN-030/IPM 041 study.
MTN-030/IPM 041 was conducted at Magee-Womens Hospital of UPMC in Pittsburgh and the University of Alabama at Birmingham (UAB), in close collaboration with IPM. The study enrolled 24 women who were randomly assigned to use either the combination dapivirine-levonorgestrel ring or a ring containing 200 mg of dapivirine alone.
In the second Phase I study, called MTN-044/IPM 053/CCN019, all participants will use the dual-purpose ring for a total of 90 days - some will use the vaginal ring continuously for 90 days, while others will use the ring cyclically (worn for 28 days and taken out for two days) over the same period of time. Meanwhile, MTN researchers have also been conducting a Phase I study (MTN-036/IPM 047) of two formulations (100 mg and 200 mg) of a 90-day dapivirine-only ring containing no contraception.
Both types of products could have important public health impact in regions like sub-Saharan Africa, where HIV is not the only risk women face. Many women also experience high rates of complications during pregnancy and childbirth, often resulting in maternal and newborn death.
"We believe in the promise of multipurpose prevention and today's results of the first study of the three-month dapivirine-contraceptive ring are welcome progress toward meeting women's overlapping sexual and reproductive health needs," said Zeda F. Rosenberg, ScD, IPM founder and CEO.
First developed for contraceptive use, vaginal rings are flexible products that are worn inside the vagina, where they release medication slowly over time.
In all, 20 oral and poster presentations will be given by MTN investigators at HIVR4P 2018, which runs Oct. 22-25. Additional presentations include two plenary talks, one of which will be given by Dr. Achilles, and a number of satellite sessions and conference symposia.
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Dr. Achilles will be presenting Safety and Pharmacokinetics of Dapivirine and Levonorgestrel Vaginal Rings for Multipurpose Prevention of HIV and Pregnancy (OA12.02LB) on Wednesday 24 October (13:15-13:30) during Oral Abstract Session 12 - Contraception and HIV Risk: Still Between a Rock and a Hard Place. She will also be discussing the study's results at an official HIVR4P press conference on Thursday 25 October from 12:00-13:00 CET. All conference sessions will be available for playback on the HIVR4P website. Press conferences will be live-streamed on the HIVR4P Facebook page and also be available for playback on the conference website.
MTN-030/IPM 041 and the MTN are supported by the U.S. National Institutes of Health grants UM1AI068633, UM1AI068615, UM1AI106707.
About the Microbicide Trials Network
The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners whose work is focused on the rigorous evaluation of promising microbicides - products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV - from the earliest phases of clinical study to large-scale trials that support potential licensure of these products for widespread use. More information about the MTN is available at http://www.mtnstopshiv.org/.
Dapivirine, also known as TMC-120, belongs to a class of ARVs called non-nucleoside reverse transcriptase inhibitors that bind to and disable HIV's reverse transcriptase enzyme, a key protein needed for HIV replication. IPM holds an exclusive worldwide license for dapivirine from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), which is designed to ensure that women in low-resource settings have affordable access to any dapivirine-based microbicide. For more information about the dapivirine ring, go to www.ipmglobal.org.
"Almost 200 women in sub saharan africa by this afternoon by the end of this session would get infected with HIV...on daily basis more than 1500 women are getting infected"