“This is an incredibly exciting milestone in our clinical trial,” said AGT CEO Jeff Galvin. “We demonstrated our theory in pre-clinical tests in cell models, and published encouraging data in Molecular Therapy Magazine. Now we’re seeing blood markers in trial participants that indicate parallel data in vivo.”
This augments the safety data already established in the human trial with initial markers of efficacy in the participants’ blood tests. The probative data is still to come in treatment withdrawal studies, which are planned to begin in the first half of 2022. AGT continues to hope to see a functionally cured patient by next summer that durably suppresses their viremia without the use of antiretroviral therapy (ART). The company remains optimistic that its work may allow people living with HIV to go off ART without fear of developing AIDS or infecting others, and without the risk of reinfection.
“Our goal is to return people living with HIV to a normal life without the side effects of ART, and having no further consequences of their HIV infection,” added Galvin. “We believe it is possible for a one-and-done therapy to make a person living with HIV permanently immune to HIV, and this recent data increases our optimism that we are on track.”
Phase 1 Trial Background
Overview: Designated the RePAIR trial (Restore Potent Antiviral Immune Responses, NCT04561258), AGT’s first-in-human study for AGT103-T is currently underway at trial sites in the Maryland / Washington, D.C. area. Participants in the Phase 1 trial receive a single infusion of their own HIV-specific CD4 T cells after those cells are enriched and genetically modified to resist infection. Without any observed negative or adverse events, the DSMB has allowed the trial to continue without adjustments or delays.
Focus: The primary endpoints of RePAIR are safety and efficacy. Testing related to secondary endpoints evaluates responses to treatment, including changes in the immune response to HIV. Participant Criteria: Participants range in age from 18 to 60 and include males and females.
Participants have been diagnosed with HIV for at least three years and must have taken HIV antiretroviral medication for more than two years prior to enrollment. Participants cannot be pregnant and must be available to attend 17 study visits over a 10-month period. Anticipated completion of treatments in the Phase 1 study is Q2 2022, although final data and long-term monitoring will continue. The Phase 1 study will include 18 participants. (The recruitment status of the Phase 1 RePAIR clinical trial, along with information on the trial sites, can be found on the official ClinicalTrials.gov website.)
Timeframe: Participants treated with AGT103-T are followed for 6 months in this safety study before enrolling in an FDA-mandated, 15-year, long-term follow up (required for all gene therapy trials). The first infusion occurred in May 2021, the second in August 2021, the third in September 2021, and the fourth and fifth in November 2021. Two more are scheduled for January 2022. AGT is also submitting a modification to the protocol with the intention of starting a treatment withdrawal study in March 2022.
According to UNAIDS, approximately 37.7 million people worldwide live with HIV/AIDS. In the United States, government statistics show 1.2 million people have HIV and estimate that 34,800 Americans were newly infected with HIV in 2019. Across the globe, UNAIDS estimates that approximately 1.5 million individuals were newly infected with HIV in 2020. The Washington D.C./Baltimore area is often cited as a ‘hot spot’ for HIV, with Washington, D.C., having the highest rate of infection at nearly 46 cases per 100,000 population and Baltimore City having rates of 17 cases per 100,000. Maryland also ranks sixth among U.S. states and territories in HIV diagnosis rates, with more than 900 new cases in 2019 alone, according to the Maryland Department of Health.
Since the late 1980s, antiretroviral drugs have restored quality of life to persons living with HIV and, in some cases, have even been used to prevent new infections. However, no approved treatment has demonstrated the ability to cure HIV. AGT is committed to addressing this unmet medical need.
AGT103-T is a genetically modified cell product made from a person's own cells. AGT's unique approach focuses on permanently repairing the key immune system damage caused by HIV. AGT’s goal is to develop a cell and gene therapy capable of repairing the immune system so it will provide natural control over HIV replication. About American Gene Technologies AGT is a gene and cell therapy company with a proprietary gene-delivery platform for rapid development of cell and gene therapies to cure infectious diseases, cancers, and inherited disorders. AGT's mission is to transform people's lives through genetic medicines that rid the body of disease. AGT has been granted four patents for the technology used to make AGT103-T and 11 patents for its unique immuno-oncology approach to stimulate gamma-delta (γδ) T cells to destroy a variety of solid tumors. The company has developed a synthetic gene for treating Phenylketonuria (PKU), a debilitating inherited disease. AGT's treatment for PKU has been granted Orphan Drug Designation by the Food and Drug Administration (FDA), and it is expected to reach the clinic in 2022.