Breakthroughs Blog: FDA

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. Scientists at the Icahn School of Medicine at Mount Sinai and research partners have developed an innovative antibody platform to tackle viruses like SARS-CoV-2 (the virus that causes COVID-19) that can rapidly evolve and render vaccines and treatments ineffective. The platform uses engineered nanobodies to simultaneously target multiple stable regions of the virus that are less likely to mutate, making it harder for resistance to develop. While most therapeutic antibodies target only a single viral site and can lose effectiveness within a year as viruses evolve, this platform has the potential to offer a more durable, resilient defense against these tricky viruses. It could also be potentially adapted to target other pathogens. In lab tests and experiments in mice, the platform was able to effectively target a range of variants of the SARS-CoV-2 virus and even the closely related SARS-CoV virus. A new research project led by researchers at the Barcelona Institute for Global Health and Columbia University aims to develop a lateral flow test for diagnosing malaria at the point of care that would also enable health care workers to determine the severity of the disease and decide whether a course of treatment is necessary. While some patients with uncomplicated malaria can be treated at home, malaria can also rapidly progress and require more complicated treatment in a health care setting. Lateral flow tests for malaria diagnosis exist, but parasite counting using microscopy is needed to determine severity and that cannot be done at the point of care. The researchers, who hope to have a validated prototype by the fall of 2026, are looking to develop a portable, paper-based assay that uses a smartphone and can deliver results within minutes.   Last Monday, Roche announced that its mpox assay, Cobas MPXV, has been listed under the World Health Organization’s (WHO’s) Emergency Use Listing procedure, a designation that aims to accelerate the availability of and access to the test during the current global mpox emergency. The automated real-time PCR-based test detects DNA from the virus that causes mpox using a dual-target approach and previously received Emergency Use Authorization from the US Food and Drug Administration in 2022. Earlier this month, Abbot’s mpox test was also listed on the Emergency Use Listing procedure following a call by WHO for manufacturers to submit expressions of interest back in August.

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. Last week, scientists in Rwanda and partners from the World Health Organization launched the world’s first clinical trial testing a treatment for the deadly Marburg virus amid the ongoing outbreak in the country. There are currently no approved treatments or vaccines against Marburg virus, although a clinical trial of Sabin Vaccine Institute’s investigational vaccine is currently underway in Rwanda. The new trial will investigate the safety and efficacy of remdesivir and the monoclonal antibody MBP091, developed by Mapp Biopharmaceutical with support from the Biomedical Advanced Research and Development Authority.  At the recent G7 Joint Finance and Health Ministers’ Meeting, the Italian government announced a $21 million commitment over the next three years to the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to accelerate the development of innovative products to prevent, diagnose, and treat drug-resistant bacterial infections. AMR is a growing public health crisis, particularly in low- and middle-income countries, and there is an urgent need for international collaboration and investment to revitalize an inadequate clinical pipeline and ensure new antimicrobials, antimicrobial alternatives, and diagnostics are available for patients worldwide.Valneva and LimmaTech announced last week that their Shigella4V (S4V) vaccine has been awarded Fast Track designation by the US Food and Drug Administration. There are no approved vaccines for the Shigella bacteria, which causes shigellosis, the second leading cause of fatal diarrheal disease globally, particularly among children in low- and middle-income countries. S4V is the world’s most clinically advanced tetravalent bioconjugate vaccine for shigellosis. This designation will enable accelerated clinical development and review of the vaccine, which will be investigated in two Phase 2 trials that are expected to begin before the end of 2024.

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.