Gene-editing therapy PBGENE-HBV shows encouraging trial results
Early study data show top dose nearing cure-testing mark in hepatitis B
PBGENE-HBV, Precision BioSciences’ experimental gene-editing therapy for chronic hepatitis B, showed antiviral activity across three doses, with the highest dose approaching the benchmark needed to consider stopping standard antiviral medications and testing for a potential cure.
That’s based on data from nine adults with chronic hepatitis B in the Phase 1 ELIMINATE-B clinical trial (NCT06680232), which is assessing PBGENE-HBV’s safety, pharmacological properties, and antiviral activity against the hepatitis B virus (HBV). The study is still recruiting participants at sites in the U.S., New Zealand, Hong Kong, and Moldova.
“We feel the data coming out of [the high-dose group] represents a near-term path towards stopping [standard antiviral medication], testing for cure, and then moving into [the trial’s] Part 2 dose-expansion,” Cassie Gorsuch, PhD, Precision’s chief scientific officer, said during a recent company webcast announcing the trial’s latest results.
Early clinical results mark a milestone in hepatitis B research
The interim findings were also shared in an oral presentation at this year’s American Association for the Study of Liver Diseases meeting, held Nov. 7-11 in Washington, D.C.
“These new … data represent a milestone for Precision BioSciences and for the entire field of chronic hepatitis B,” Michael Amoroso, CEO of Precision, said in a company press release.
In hepatitis B, liver inflammation results from infection with HBV. When the infection becomes chronic — lasting six months or longer — it can lead to serious liver damage. Antiviral medications can lower the amount of virus in the blood, but they cannot fully stop it from replicating its DNA within liver cells.
PBGENE-HBV, administered through intravenous (into-the-vein) infusions, is designed to delete or inactivate all forms of HBV DNA inside infected liver cells. Delivered to liver cells using tiny fat-based carriers, the therapy works by cutting covalently closed circular DNA (cccDNA) — which acts as template to produce more virus — and the virus’ genetic material that’s been integrated into the cells’ own DNA.
These two forms of viral genetic material can keep the infection active even after years of treatment. By inactivating both, PBGENE-HBV aims to eliminate the source of infection and offer a potential cure — meaning the virus could be suppressed enough that antiviral medications are no longer needed.
The two-part ELIMINATE-B trial is evaluating PBGENE-HBV in up to 45 adults, ages 18-70, who have had hepatitis B for at least a year, are on stable antiviral medications, and test negative for HBeAg, a protein that indicates the virus is actively replicating in the body.
Trial tests escalating doses to assess safety and viral response
In the first part, three dose levels are being tested sequentially in small groups of three patients each. Each participant may receive up to three infusions at intervals of eight weeks. The safest and most effective dose will then be tested in more patients during the study’s second, dose-expansion part.
As of the end of last month, nine participants had received a total of 22 infusions across the three dose levels (0.2, 0.4, and 0.8 mg/kg). PBGENE-HBV was generally well tolerated, with side effects described as “predictable and manageable,” and “consistent with infusion related reactions,” according to the company’s presentation.
All nine participants showed signs of antiviral activity. Reductions in HBsAg — a viral protein that indicates infection — were seen even in those who began with very high HBsAg levels. Higher doses led to stronger and more lasting suppression of viral activity.
As reported earlier, two participants in the lowest dose group (0.2 mg/kg) showed a reduction in HBsAg within two weeks of the first dose. The third person in this group responded later, but their HBsAg remained reduced by half nine months after the first dose. At the 0.4 mg/kg dose, all three people had lasting reductions, of up to 66%, that continued after repeat dosing.
The highest dose group (0.8 mg/kg) showed the fastest and strongest responses, with large HBsAg reductions seen within two weeks of the first dose. One person received two doses and had a stronger response after the second, showing a 64% reduction in HBsAg that remained low between doses — unlike what was observed in lower-dose groups.
High-dose group continues to show deeper antiviral responses
With more doses to come and expected to complete in early 2026, all three people in the high-dose group “continue to demonstrate deepening responses towards benchmark to consider stopping [antiviral medications] to test for cure,” the company wrote in its presentation.
A liver biopsy — a piece of liver tissue collected for examination under a microscope — from a participant in the middle dose group showed that PBGENE-HBV had cut and inactivated HBV DNA at the intended target, confirming the therapy worked as designed.
Once Precision determines the dose and schedule that allow patients to stop their antiviral medication, it plans to test that optimized PBGENE-HBV regimen in the trial’s second part, which will include a larger group of participants. The company also plans to test a shorter, four-week interval between doses instead of the current eight weeks.
About the Author
