- A gene editing treatment for HIV was safely given to the first three adults enrolled in a small clinical trial, the therapy’s developer, Excision BioTherapeutics, said Wednesday.
- Initial results from the study, presented at the European Society for Gene & Cell Therapy in Belgium, showed no serious side effects or toxicity that would limit treatment. Two of the three study participants had “transient and reversible” elevations in their liver enzyme counts, which are carefully watched as a warning sign of possible safety risks.
- Excision plans to increase the dose of its therapy, dubbed EBT-101, for evaluation in the next phase of the Phase 1/2 trial, which is set to enroll nine participants in total. The private San Francisco-based biotechnology company expects to report more trial data next year.
Excision’s results are early, from only a few treated individuals and don’t show whether EBT-101 actually might be effective as a treatment for HIV.
Still, they offer a glimpse at how one of the few “in vivo” gene editing treatments cleared by the Food and Drug Administration for human testing is working.
Unlike gene editing therapies that modify the DNA of cells in a laboratory, in vivo treatments do their editing work inside the body and are therefore considered more risky. Along with Excision’s therapy, the FDA has given a green light to testing of in vivo treatments from Sangamo Biosciences, Intellia Therapeutics and Verve Therapeutics. (Sangamo has since terminated its study.)
EBT-101 is also an ambitious application of CRISPR/cas9 technology. Excision’s treatment delivers into the body, via an adeno-associated virus, a DNA-cutting enzyme and two strips of RNA that act as a guide to direct the editing to sites on the HIV genome. Once cut, the virus should be unable to replicate. Excision intends for EBT-101 to be a functional cure for HIV.
Currently, antiretroviral treatment can effectively suppress the HIV virus and thereby prevent progression to AIDS. But available drugs don’t eliminate HIV that hides in pockets of the body known as viral reservoirs, a shortcoming EBT-101 could in theory address.
Excision is enrolling HIV-infected adults who are stable on antiretroviral therapy into its study, which is taking place at sites in California, Missouri and New Jersey.
Four mild adverse events judged to be related to treatment were reported in the first three treated participants, all of which resolved without medical intervention, Excision said. Two were liver enzyme elevations, while the other two were fatigue and low white blood cell counts.
There were no reactions related to EBT-101 infusion and no complement-mediated toxicity.
EBT-101 was detectable in the blood four weeks after infusion in all three participants, and Excision reported no evidence of the gene vector in tissue associated with male reproductive function. The company will continue to evaluate biodistribution of EBT-101 in the blood through the 48 weeks of the study, and expects to present updated findings in 2024.
“Establishing the safety and biodistribution of EBT-101 is an important first step in the clinical program,” said William Kennedy, Excision’s head of clinical development, in a statement. “These initial observations provide important clinical data that support the advancement of the EBT-101-001 trial to the next dosing cohort.”
Excision plans to launch the next dose cohort this quarter.