Excision’s CRISPR-Based HIV Treatment Fails to Show Curative Potential in Early Study
Gene TherapyPhase 1Clinical ResultsiRNA
Pictured: 3D illustration of the CRISPR-Cas9 system editing a stretch of DNA/iStock, Meletios Verras
Excision BioTherapeutics’ attempt to use a CRISPR-based gene editing therapy to cure HIV has failed an early-stage study, according to several media reports on Friday.
Results from the Phase I trial of five patients showed that Excision’s CRISPR therapeutic did not strongly suppress the HIV virus. Three patients who were taken off of antiretroviral therapy soon developed viral rebound and needed to resume conventional treatments, according to reporting by STAT News.
Still, Excision’s approach did show signs of promise. One patient was able to keep the virus at bay for 16 weeks after stopping antiretroviral treatment before rebounding. Typically, HIV levels resurge after around four weeks. The experimental CRISPR treatment also appears to have lowered the number of infected cells in this patient, according to STAT.
In response to the disappointing outcome, CEO Daniel Dornbusch told STAT that Excision is “encouraged” by the safety data in the Phase I study, which suggests that “in-vivo CRISPR can be done in a safe way in humans.” The company will use these findings to work on a new gene editing candidate that it can apply to other chronic viral infections, such as herpes and hepatitis B.
According to its website, Excision’s lead candidate is EBT-101, a CRISPR-based gene editor that works by cutting out the HIV pro-viral DNA from all infected cells. The candidate is delivered via an AAV9 vector and uses two guide RNAs that can home in on three target sites in the HIV genome, minimizing the likelihood of viral escape.
The company is positioning EBT-101 as a potentially curative treatment for chronic HIV and is “rapidly advancing toward clinical trials.”
In October 2023, Excision released safety data from its first-in-human Phase I/II study of EBT-101, showing that there were no serious adverse events or dose-limiting toxicities in all three patients that had been dosed with the gene editor at the time. The study found four mild toxicities that could be potentially related to EBT-101, though all were resolved without intervention.
The early data also showed that EBT-101 was present at detectable levels in the blood four weeks after treatment.
In addition to targeting HIV, Excision is also leveraging its proprietary CRISPR-based gene-editing platform against herpes 1 and 2, for which it is advancing EBT-104, and hepatitis B, for which it is developing EBT-107.
Several biotech companies have responded to the HIV crisis, including industry powerhouses Gilead and GSK. Gilead owns the oral antiretroviral pill Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), while GSK and partner ViiV Healthcare market the oral pill Tivicay (dolutegravir) and long-acting injectable Cabenuva (cabotegravir/rilpivirine).
While these virus-suppressive treatments are effective, a true cure remains elusive and the field continues to face several substantial challenges. In March 2024, the World Health Organization warned of a growing virus resistance against Tivicay.
Meanwhile, gene therapies which have strong curative potential still pose potential safety concerns, particularly unintended edits and off-target effects.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
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