Vesatolimod

Long known for its HIV drugs, Gilead is further delving into the field by acquiring investigational vaccines for the stubborn virus from a little-known biotech in Spain. Gilead is paying an undisclosed amount to buy HTI T cell immunogen HIV vaccines from Barcelona-based Aelix Therapeutics, a spinout from a Catalan public-private program created to find a vaccine for the virus. The companies declined to disclose deal terms. In the HIV epidemic’s 40-plus-year history, a vaccine has never made it across the regulatory finish line, continuously puzzling researchers and drugmakers. Many treatments exist, as do effective preventative measures like PrEP, but a vaccine remains elusive as HIV can stealthily hide from the immune system in reservoirs. Johnson & Johnson suffered two mid- and late-stage failures in 2021 and 2023 . Gilead is getting its hands on experimental HIV vaccine assets from Aelix, which has taken a regimen through Phase 2a. The startup tested its T cell vaccines ChAdOx1.HTI and MVA.HTI along with Gilead’s toll-like receptor agonist, known as vesatolimod, in people with HIV who were taking antiretroviral therapy, or ART. The Phase 2a study , dubbed AELIX-003, wrapped up in late 2022. Researchers said the regimen was “safe and well tolerated” with “high levels of HTI-specific T-cell responses,” according to a presentation at the Conference on Retroviruses and Opportunistic Infections in February 2023. Further, 10 of 30 AELIX-003 participants on the vaccine-vesatolimod regimen were able to stay off ART for 24 weeks. In the placebo group, four of 17 participants were able to do so, according to a press release . “The HTI vaccines have shown promising results in Phase 1 and Phase 2 clinical trials, and we are eager to see this immunogen move forward through this acquisition and potentially become an important aspect of the search for an HIV cure,” Aelix chair Thomas Hecht said in a Monday statement . The epidemic is still far-reaching, and a vaccine is seen as a critical way to finally bring it to an end. About 39.9 million people lived with HIV at the end of 2023, a year in which another 1.3 million new cases were reported. About 630,000 people died last year from HIV-related causes, according to the World Health Organization. HIV drugs are a core part of Gilead’s portfolio. Its HIV medicines, including Biktarvy and Descovy, made $5.1 billion in the third quarter, or about 68% of the company’s total sales in that period. But advocates have called for greater access to the drugmaker’s treatments and PrEP medicines, which they say are too costly and not readily available. The California biopharma made international headlines earlier this year when it said its twice-a-year injection of lenacapavir fully prevented HIV in cisgender women. The shot succeeded in another pivotal trial in September. Gilead is also working on multiple other programs, including long-acting oral inhibitors and injectables, a bispecific T cell engager and a once-weekly pill. The pill, a combination of lenacapavir and Merck’s islatravir, is entering two Phase 3 trials, the companies said last month. Gilead can also opt into programs from Gritstone bio and Hookipa Pharma. Aelix derives from HIVACAT, a Catalan program focused on HIV vaccines involving the IrsiCaixa AIDS Research Institute and Hospital Clínic de Barcelona. Ysios Capital and 10K Lakes Capital, among others, have backed Aelix.

April 19, 2024 -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the opening of A5374, a phase 1/2a study evaluating the safety, tolerability, and antiviral effect of a novel combination regimen that includes therapeutic T-cell vaccines, two broadly neutralizing antibodies (bNAbs), and an immune-system boosting treatment among people living with HIV who started antiretroviral treatment (ART) during acute (early) HIV infection. A5374 (Triple Immune Strategy for HIV Remission) is a multi-site, randomized, placebo-controlled trial. The study hypothesizes that this combination regimen will be safe and result in a longer period of viral control during a closely monitored pause in ART (known as an analytic treatment interruption) compared to placebo. While current ART can manage HIV very well, it does not cure it and people living with HIV have to take it for the rest of their lives in order to suppress viral replication and protect their immune systems. The approach being studied in A5374 is part of a potential path toward enabling the immune system to manage HIV in the absence of ART for weeks or months. “We expect that controlling HIV in the absence of ART will require a combination of novel treatments to decrease the number of cells harboring HIV and simultaneously stimulate the immune system to keep the virus from replicating,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles. “A5374 is a pivotal trial and we are hopeful that it will provide us with important insights into how to boost the immune system so that it can control HIV.” A5374 will enroll 45 participants aged 18 years and older who started combination ART within 28 days of acute HIV diagnosis (30 who will receive active study treatment and 15 who will receive placebo). The study will last up to approximately two years for each participant. After enrollment, participants will continue taking their HIV medications and will either receive a series of novel treatments or placebo. The novel regimen includes a T-cell vaccine regimen (vaccines vectored by replication-deficient chimpanzee adenovirus ChAdOx1 and poxvirus MVA, each containing six small fragments of HIV); broadly neutralizing antibodies (teropavimab, also known as GS-5423 or 3BNC117-LS, and zinlirvimab, also known as GS-2872 or 10-1074-LS); and vesatolimod (a toll-like receptor 7 or TLR7 agonist, which acts as an immune booster). After about 16 months in the study, participants will stop taking ART. They will be closely monitored for increases in HIV viral load, decreases in CD4 T-cell counts, and symptoms, and will resume taking ART if there is a signal that HIV is rebounding or if they become pregnant. The study will compare the length of time that participants in the active treatment and placebo groups experience viral control while they are off ART. “Our goal with this study is to demonstrate that enhancing immune responses to HIV will lead to sustained suppression of HIV during treatment interruption,” said A5374 Protocol Chair Sharon A. Riddler, M.D., M.P.H., University of Pittsburgh. Carefully monitored analytic treatment interruptions are an important part of HIV cure clinical trials. They can help determine whether a research intervention can reduce latent HIV (HIV that is “hidden” in different cells and tissues but not replicating) or increase immune function and delay or prevent latent HIV from actively replicating. A5374 will take place at up to 10 sites in the United States and Brazil. It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (which also funds ACTG), under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. The University of Oxford is supplying the T-cell vaccines and conducting endpoint assays. Gilead Sciences is supplying the bNAbs and TLR7 agonist. A5374 is led by Dr. Riddler and Cynthia L. Gay, M.D., M.P.H., University of North Carolina (UNC) (Co-vice Chair) and John Mellors, M.D., University of Pittsburgh (Co-vice Chair). ACTG is led by Dr. Currier and Joseph J. Eron, M.D., UNC (ACTG Vice-Chair). ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. The content above comes from the network. if any infringement, please contact us to modify.