Breakthroughs Blog: FDA

An estimated 257 million women globally who want to avoid pregnancy are not using safe, modern contraceptive methods, leading to around 121 million unintended pregnancies globally every year—nearly half of all pregnancies. Ensuring all who wish to use contraception have access to safe, effective, and acceptable options can enable all people of reproductive potential to enjoy greater autonomy over their lives and health. To meet the diverse needs of people of reproductive age, we need a variety of new contraceptive choices, including options that are longer-lasting, more discreet, have fewer side effects, and require fewer visits to a health care provider, as well as additional options for men to take more of the burden of pregnancy prevention off the shoulders of women. In recognition of this year’s World Contraception Day, GHTC is highlighting six technological solutions in the pipeline that could enable greater access to contraception by breaking down barriers, especially for underserved populations and those in low-resource settings. 1. Next-generation contraceptive vaginal rings   Intravaginal rings—flexible silicone rings that are self-inserted into the body and release contraceptives—offer an easy-to-use, convenient, and discreet contraceptive option for many women worldwide. Today, women can choose from either a monthly or a yearly ring—the latter of which was developed by Population Council and first approved by the US Food and Drug Administration (FDA) in 2018. However, both ring options use a combination of the same estrogen hormone, ethinyl estradiol, and different types of progestin hormones. While these hormone options work well for many individuals, for others, they can cause side effects or risks, creating a need for rings with alternative hormones and rings that are nonhormonal. Thankfully, several next-generation rings are on the horizon.These next-generation options include two rings under development by Population Council, which use alternative hormones. The first, the three-month Nestorone®/estradiol intravaginal ring uses a form of estrogen that, unlike ethinyl estradiol, is not associated with an increased risk of blood clots in the veins among women with a higher body mass index—who account for 15 percent of adult women. It is currently being evaluated for use in women with a higher body mass index in a Phase 2b study.  The second, the Nestorone®-only vaginal ring, has no estrogen, offering an alternative for those who have estrogen sensitivities, those who are at higher risk of blood clots, and postpartum breastfeeding mothers, who are often advised against using hormonal contraception that contains ethinyl estradiol due to its effect on milk production and composition. The ring will soon undergo a Phase 2 dose-finding study.On the nonhormonal front, Daré Bioscience is developing Ovaprene®, a monthly vaginal ring which uses a “semi-permeable polymer mesh barrier” to physically stop sperm from entering the cervical canal. Early clinical studies found that the ring is well-tolerated and acceptable to sexually active women and their partners. Additional clinical trial results announced in 2024 also demonstrated safety and efficacy, paving the way for a Phase 3 trial now underway.2. Biodegradable contraceptive implant  Today’s contraceptive implants are small, flexible rods inserted under the skin that continuously release hormones for pregnancy prevention. While they are safe and long-lasting, after three years, they must be removed by a medical provider. That can be an issue, particularly in low-resource settings worldwide where fewer trained health care workers, distance, and cost can serve as barriers to care. Biodegradable contraceptive implants, which dissolve into the body, offer promise as a more convenient option that could improve access by cutting out the need for a trip to a medical facility for device removal.FHI 360 and development partners pH Sciences and Gesea Biosciences, with funding from the Bill & Melinda Gates Foundation, developed a biodegradable implant called Casea S, which can provide protection against unintended pregnancy for 18 to 24 months. The implant is now being tested in a Phase 1 clinical trial, the first trial for a biodegradable contraceptive implant in more than 20 years.3. Microneedle contraceptive patches   Many women choose to use injectable forms of contraception for long-acting protection, but, for others, the need for regular shots and visits to a health care provider can make this a less desirable choice. But imagine if these injections were pain-free and did not require leaving home. That is the promise of microneedle or microarray patches, which are small Band-Aid-like patches that contain hundreds of microneedles that slowly release drugs into the body when pressed against the skin. The new technology, which is also being developed to deliver vaccines and therapeutics, could offer a discrete, user-controlled, and less painful option that could either be self-administered or administered by a health care provider with minimal training.  With support from the US Agency for International Development through the US President’s Emergency Plan for AIDS Relief, PATH is developing an easy-to-use, discreet, and self-administered contraceptive patch that could provide protection against unintended pregnancy and HIV, which is currently in preclinical development.FHI 360, in partnership with Population Council and the Georgia Institute of Technology, is also developing a three- to six-month, biodegradable, and progestin-only patch currently in the preclinical phase, with support from the US Agency for International Development and the Gates Foundation.4. Longer-acting contraceptive injectablesThe most commonly used contraceptive injection, depot-medroxyprogesterone acetate (DMPA), approved by FDA back in 1992, offers a longer-lasting option than the daily pill, with a three-month period between injections. However, DMPA requires users to return often to their health care providers, and it has the highest discontinuation rate among contraceptives in the United States due to unpleasant side effects like menstrual irregularities, weight gain, and bone density loss.FHI 360 is in the midst of a Phase 3 trial testing a six-month version of DMPA that is injected under the skin rather than into the muscle, which could offer a longer-lasting, lower-dose option that is more convenient and presents a lower risk of side effects for users. The product, which is the furthest-along six-month injectable in the pipeline, could be approved as early as 2025 or 2026 if trials prove successful.  FHI 360 is also developing a six-month self-injectable contraceptive that uses levonorgestrel rather than DMPA and is being advanced through Phase 1 clinical trials in collaboration with the Shanghai Institute for Biomedical and Pharmaceutical Technologies, with funding from the Gates Foundation. This product could offer another longer-lasting option with potentially fewer side effects and the convenience of using it at home.  5. Male contraceptivesThe need for male contraceptive options beyond condoms and vasectomy to allow men to more equally share the responsibility of contraception has been widely and increasingly recognized. There are a number of technologies in development, including technologies that use hormones to disrupt the sperm creation process. Population Council has developed a novel, easy-to-use, and reversible gel hormonal contraceptive method that is applied daily to the shoulders and, if approved, would be the first-of-its-kind option for men. Early studies showed that it is well tolerated and causes no serious adverse events. A Phase 2b study yielded promising results, with a second part of the trial now underway. The gel, which could enter the final phase of testing in 2025 with the go-ahead from FDA, has made it excitingly far in a pipeline lacking in male contraceptive technologies beyond the preclinical stage.While hormonal strategies require a long time to start and stop working because of the considerable months-long sperm development process and could have side effects due to hormone disruption, there are also nonhormonal technologies in early-stage development. These nonhormonal strategies target specific processes later in sperm development and could start and stop working more quickly, perhaps even to the point of an on-demand product taken right before intercourse. One recent study in mice identified a new nonhormonal, reversible method that targets a protein complex important during sperm production, with the drug successfully stopping the process without producing side effects or causing irreversible effects. Another recent study in mice identified a different protein target necessary for fertility, finding similarly positive results.  Contraline and Next Life Sciences are also developing nonhormonal products that work by blocking the vas deferens, the tube in the male reproductive system that transports sperm, with an injectable gel. Contraline announced positive interim results from a first-in-human trial earlier this year. 6. Dual-use technologies for HIV, STI, and pregnancy preventionMultipurpose technologies that protect against unintended pregnancy, HIV, and other sexually transmitted infections (STIs) could be a game-changer in opening up access to prevention tools, particularly in low-resource settings, by reducing the burden on users and the health care system.In addition to the aforementioned microneedle patch for HIV and unintended pregnancy prevention, Population Council is developing several dual-use products. The two products likely to reach market fastest are a dual-use pill, which reformulates already approved medicines for oral pre-exposure prophylaxis and oral contraceptives into one tablet to be taken daily, and the dapivirine-levonorgestrel vaginal ring, which builds on the successful development of the one-month dapivirine ring for HIV prevention with a three-month ring that slowly releases the antiviral drug dapivirine and the contraceptive hormone levenorgestrel, drugs already approved in other forms. Other products in early development include a nonhormonal vaginal ring and a nonhormonal fast-dissolving vaginal insert, both designed to provide crosscutting protection against unintended pregnancy and STIs.Currently, contraceptive research and development is greatly underfunded, and there is an urgent need for new and improved products to better serve particular populations and those living in low-resource settings. The contraceptive technologies detailed above and others in the pipeline offer hope that we will in the future have a robust array of contraceptive options to ensure everyone globally who wants to use contraception has access to a product that works for them.  

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. On Friday, the World Health Organization (WHO) announced the prequalification of Bavarian Nordic’s MVA-BN vaccine for mpox, the first-ever vaccine for the virus on the prequalification list. Prequalification status is anticipated to facilitate timely and increased access to the vaccine, helping to contain the current outbreak on the African continent by accelerating procurement by governments and international agencies and enabling national regulatory authorities to fast-track additional approvals. The vaccine has been licensed for use in people 18 years and older with a two-dose schedule given a month apart. However, the WHO Strategic Advisory Group of Experts has specifically recommended the use of the vaccine for people at a high risk of exposure in the context of an outbreak; thus, the vaccine has been used in infants, children, adolescents, and pregnant and immunocompromised people. It has also recommended single-dose use to stretch limited supplies while also urging the need to collect additional data about the vaccine’s safety and efficacy in these circumstances.Last week, Gilead published new results from the highly anticipated PURPOSE 2 trial, the second Phase 3 study of its twice-yearly, long-acting drug for HIV pre-exposure prophylaxis (PrEP), lenacapavir. The trial showed that the drug was able to reduce HIV infections by 96 percent compared with background HIV incidence and was 89 percent more effective than Gilead’s already available PrEP drug, Truvada. The study, which included more than 3,000 cisgender men, transgender men and women, and gender non-binary individuals aged 16 and older across seven countries, was unblinded early to offer lenacapavir to all patients in the study. This news follows the exciting results from the PURPOSE 1 trial of the drug in cisgender women and adolescent girls, which demonstrated 100 percent efficacy and was also unblinded early. Lenacapavir is currently available for use alongside other agents in patients with multidrug-resistant HIV, which make up only 2 percent of adults living with HIV, but, if approved for additional populations, the drug could be available as soon as 2025 and could be a game-changer for the HIV epidemic. Emergent BioSolutions last week announced that the Biomedical Advanced Research and Development Authority (BARDA) awarded the company a $41.9 million research and development option to its existing ten-year contract to further the development, validation, commercialization, and scale-up of the company’s monoclonal antibody treatment for Ebola virus infection. The treatment, Ebanga, was initially developed by Ridgeback Biotherapeutics with support from BARDA and was approved by the US Food and Drug Administration as a single infusion for the treatment of Ebola Zaire virus infection in 2022. The award is part of BARDA’s broader strategy to support treatments that can be deployed during virus outbreaks.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. The US Food and Drug Administration (FDA) on Thursday approved updated COVID-19 vaccines from Pfizer and Moderna that target the KP.2 virus strain, which emerged from the highly contagious JN.1 variant that began circulating widely in the United States last winter. The new shots are expected to be available within days amid spiking case rates and hospitalizations for COVID-19. Experts also hope the vaccines will provide cross-protection against closely related subtypes of the virus, including KP.3.1.1 and KP.3, which are now spreading rapidly and account for 36 and 17 percent of all new cases, respectively. The FDA has not yet approved a third vaccine from drugmaker Novavax.The World Health Organization (WHO) this week recommended three new oral regimens for multidrug-resistant or rifampicin-resistant tuberculosis (TB) that can cure patients more quickly and successfully than the current painful injectable regimens. These regimens—which include the use of new and repurposed medicines like bedaquiline, pretomanid, linezolid, and delamanid—can be offered to nearly all patients and can improve treatment success by shortening treatment time to six to nine months, rather than the usual 18 months, while reducing treatment toxicity and the spread of drug-resistant forms of TB. WHO’s recommendations are based on results from the BEAT-TB clinical trial conducted in South Africa and the endTB trial conducted in seven countries between 2017 and 2023 by Médecins Sans Frontières, Partners In Health, and Interactive Research and Development and funded by Unitaid.  A new study found that giving azithromycin to all children up to five years old can greatly reduce childhood mortality in sub-Saharan Africa, more so than by limiting the distribution of the antibiotic to younger children, as recommended by WHO. The study, published Wednesday in the New England Journal of Medicine, found that twice-yearly distribution of azithromycin to children ages 1 to 59 months in rural communities in Niger reduced childhood mortality by 14 percent when compared with children who received a placebo. Further, the study found that targeting only children ages 1 to 11 months (recommended by WHO in 2020) did not lead to a significant reduction in childhood mortality. However, concerns remain about the effect of routinely distributing the antibiotic to all children under five on antimicrobial resistance. 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. A team led by US Food and Drug Administration researchers last week published findings suggesting that three vaccines, already approved and stored in the Strategic National Stockpile, targeting earlier H5N1 clades that circulated in the early 2000s could provide some cross-neutralizing antibodies against the currently circulating 2.3.4.4b clade, which continues to infect dairy herds and some farm workers across the United States. Federal officials are already implementing a plan to produce 4.8 million doses of an updated vaccine targeting the current clade, with the first doses expected to be delivered this month, but, before being administered to people, the shots would still need to get regulatory approval. These new study results offer hope that the old vaccines could provide some protection if there is a need to start vaccinating humans before the updated vaccines become available.Recently published results from a Phase 2 clinical trial conducted in Sudan by the Drugs for Neglected Diseases initiative and the Institute of Endemic Diseases at the University of Khartoum found promising results for a new and improved treatment for people with post-kala-azar dermal leishmaniasis (PKDL), a serious condition that can develop after treatment for visceral leishmaniasis. The current treatment for PKDL is an injectable drug given for two to three months, which can cause life-threatening toxicity and must be administered under close supervision in a hospital. The new treatment is safer, shorter, cheaper, more effective, and more patient-friendly, only requiring patients to be admitted to the hospital for 14 days followed by an oral treatment that can be completed at home, offering hope of a new and improved tool for PDKL for affected populations, like in Sudan where nearly 20 percent of patients treated for visceral leishmaniasis will develop PKDL within six months post-treatment, the highest rate worldwide.The Sabin Vaccine Institute and the Makerere University Water Reed Project recently launched a Phase 2 clinical trial testing Sabin's vaccine against Sudan ebolavirus, which can cause deadly disease, as seen in the recent outbreak in Uganda that ended only last year. Although Sabin’s vaccine was one of three candidates chosen to be included in a trial during the outbreak, the outbreak ended before the trial could begin. The vaccine candidate, which is based on the same platform as Sabin’s Marburg vaccine candidate that is already undergoing its own Phase 2 trial, was found to be safe and elicit rapid, robust, and long-lasting immune responses in Phase 1 clinical and nonclinical studies. There is currently no approved vaccine for Sudan ebolavirus.