HIV Gene Editing Clinical Trial Treats First Patient


The patient is expected to qualify for analytical treatment interruption of background anti-retroviral therapy.

The first patient has been dosed in a phase 1/2 clinical trial (NCT05144386) of Excision BioTherapeutics’ EBT-101, an in vivo CRISPR-based gene editing approach intended for the treatment of human immunodeficiency virus type 1 (HIV-1).

EBT-101 functions by delivering CRISPR-Cas9 and dual guide RNAs via an adeno-associated virus (AAV), targeting 3 sites in the HIV genome for excision, with the intention of minimizing viral escape. According to Excision’s announcement, the first patient’s dosing occurred in July of this year and the therapy has been well-tolerated in the time since then. The patient is expected to qualify for analytical treatment interruption (ATI) of background anti-retroviral therapy (ART). EBT-101 previously demonstrated positive efficacy data in transgenic mice and positive long-term safety data in non-human primates.

“Dosing the first participant with EBT-101 is a landmark event that solidifies Excision’s position as a pioneer in gene editing,” Daniel Dornbusch, chief executive officer, Excision, said in a statement regarding the news. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”

The open-label, multicenter study is expected to enroll approximately 9 male patients aged 18 years to 60 years with documented chronic HIV-1 infection. Participants must be on a stable ART regimen for more than 2 years prior to screening and must have plasma HIV-1 RNA levels below the limit of quantification. Patients are additionally required to have a body weight between 45 and 90 kg (inclusive) and must be vaccinated for N. meningitidis and COVID-19. Patients who have had drug resistance to 2 or more classes of ART within the past 5 years, patients with more than 1 change in ART due to virologic failure in the past 2 years, and patients receiving long-acting injectable ART will be excluded from the study, as will patients with anti-AAV9 serum neutralizing antibodies greater than 1:20 titer. Patients with a history of HIV dementia or HIV-related cardiac disease, HIV-related kidney disease with abnormal renal function, or HIV-related opportunistic infections within the past 2 years will also be excluded. Additional exclusion criteria relate to past treatments and health status.

Participants will be divided among 3 cohorts and will receive a single dose of EBT-101 intravenously at 1 of 3 dose-levels, depending on their cohort. Twelve weeks after administration, eligibility for ATI will be assessed. The primary end point is the incidence and severity of adverse events. The trial will also evaluate biodistribution, pharmacodynamics, and efficacy. The study is taking place at multiple locations in the United States and is expected to be completed in March 2025. Participants will also be enrolled in a long-term follow-up study (NCT05143307), which will follow the patients for up to 15 years.

“There are nearly 40 million people worldwide suffering from the effects of HIV with no curative treatments available more than 40 years after its discovery,” Kamel Khalili, PhD, chair, Department of Microbiology, Immunology and Inflammation, director, Center for Neurovirology and Gene Editing, director, Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine at Temple University, co-founder, Excision, added to the statement. “We believe EBT-101 can address the long-standing unmet needs of people living with HIV by removing HIV DNA from their cells, thereby eradicating their infections. We believe we are well-positioned to collect key data that will enable our efforts to translate the success this approach has shown in animal models to human clinical trial participants. We look forward to investigating this hypothesis through the EBT-101 clinical program and are pleased that the EBT-101 phase 1/2 trial is proceeding as planned.”

Excision Biotherapeutics doses first participant in EBT-101 phase 1/2 trial evaluating EBT-101 as a potential cure for HIV. News release. Excision BioTherapeutics, Inc. September 15, 2022. 
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