HIV Gene Therapy Gets Go-Ahead for Early-Phase Trial


A phase 1 trial of a cell therapy for HIV is also currently underway.

Excision BioTherapeutics has received FDA clearance for its investigational new drug application for EBT-101, an investigational CRISPR-based gene therapy for the potential treatment of human immunodeficiency virus (HIV).1

“The clearance of our IND application for EBT-101 represents an important milestone for Excision and is the result of years of commitment to developing a functional cure for individuals living with HIV,” said Daniel Dornbusch, MPH, chief executive officer, Excision, in a statement.1 “Although antiviral treatments can manage HIV infection, they require life-long treatment, cause side effects, and do not provide the possibility of a functional cure. We are grateful for the FDA’s engaged review and acceptance of the IND for EBT-101 and look forward to initiating the Phase 1/2 clinical trial later this year.”

EBT-101 is an in vivo gene therapy designed to excise HIV proviral DNA. It previously demonstrated the ability to excise HIV proviral DNA across human, non-human primate, and other animal cell lines in preclinical studies. The 1-time treatment uses an adeno-associated virus (AAV) vector for delivery, guide RNAs to target 3 sites in the HIV genome, and CRISPR-Cas9 to excise portions of it and minimize viral escape. Following the FDA clearance, Excision plans to initiate a first-in-human phase 1/2 clinical trial to evaluate the safety, tolerability, and efficacy of EBT-101 in people with HIV. 

“EBT-101 has demonstrated removal of proviral DNA in multiple animal models and offers an opportunity for individuals living with HIV to potentially cease life-long therapies. The Excision team looks forward to this important collaboration with our principal investigators, scientific advisors and regulators, to conduct a safe and informative trial with this first-in-class approach to a viral disease target previously considered to be incurable,” Lisa Danzig, MD, chief medical officer, Excision BioTherapeutics, added to the statement.1

READ MORE: Zaia Draws on Decades of Innovation in Infectious Disease for Breakthroughs in Gene Therapy

The announcement follows initial dosing in American Gene Technologies’ (AGT) phase 1 RePAIR trial (NCT04561258) of AGT103-T, a cell therapy for the potential treatment of HIV, in May 2021.2 The autologous cell therapy is designed to repair the T helper cells and provide durable virus control. It can withstand HIV strains that vary in sequence or use alternate ways to enter and infect T cells.

The trial, which is still recruiting with an expected enrollment of 6 participants, is being conducted across sites in Maryland and Washington DC. Study completion is expected in September 2022. AGT’s Data and Safety Monitoring Board voted unanimously in July 2021 to continue the trial, dubbed the HIV Cure program, without modifications, after a safety analysis revealed no adverse events arising from the therapy.3

“Safety represents a critical milestone in the project and gives us additional confidence that HIV can be cured,” said Jeff Galvin, chief executive officer, AGT, in a statement.3 “This milestone supports AGT’s mission to relieve suffering and premature death from serious human diseases. AGT’s HIV cure program is based on a platform that has the capacity to treat other chronic viral infections, as well as monogenic disorders and cancers... A success in HIV would provide sustained funding to accelerate dozens of therapeutics that are within the scope of AGT’s technology platform.”

AGT has also stated that the National Institute of Allergy and Infectious Diseases has replicated their data in its labs, validating the therapy’s potential.2 They also claim that AGT103-T will yield nearly 2000 times the number of HIV specific immune cells protected and returned to the participants than a previous clinical trial by Sangamo Therapeutics, whose trial was effective in 10% of the treated patients.4

1. Excision receives FDA Clearance of IND for phase 1/2 Trial of EBT-101 CRISPR-based therapeutic for treatment of HIV. News release. Excision BioTherapeutics. September 15, 2021.
2. AGT announces progress with HIV Cure program, phase 1 clinical trial. News release. American Gene Technologies. May 27, 2021.
3. HIV Cure program releases initial clinical trial data. News release. American Gene Technologies. July 16, 2021.
4. Tebas P, Stein D, Tang WW, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 2014; 370:901-910. doi: 10.1056/NEJMoa1300662
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