Phase 1 trial of gene-editing therapy for hepatitis B cleared in US
US site to run at Liver Center at Massachusetts General Hospital
Precision Biosciences has been given the go-ahead to expand a Phase 1 clinical trial testing PBGENE-HBV, its gene-editing therapy for chronic hepatitis B, to the U.S.
Clearance by the U.S. Food and Drug Administration (FDA) “marks a significant step forward in our mission to advance potential curative treatment options for hepatitis B patients,” Murray A. Abramson, MD, Precision’s head of clinical development, said in a company press release.
The Phase 1 trial, called ELIMINATE-B (NCT06680232), was launched last year and is already recruiting participants at sites in Hong Kong, Moldova, and New Zealand. With FDA clearance now secured, Precision is actively working to get the trial up and running at the Liver Center at Massachusetts General Hospital, in Boston.
“We look forward to accelerating patient access to the study by initiating the trial in the U.S. and later expanding to the U.K.,” Michael Amoroso, Precision’s president and CEO, said in a separate company press release. “Clinical data updates will continue to be shared throughout 2025 at meaningful timepoints.”
News that the trial will be expanding to the U.S. was welcomed by the Hepatitis B Foundation.
Up to 2.4M people with chronic hepatitis B in U.S.
“Millions of people are eager for new treatment approaches that can help reduce the burden of hepatitis B which includes liver damage, liver cancer, premature death and social stigma,” said Chari A. Cohen, the foundation’s president. “In the U.S. alone there [are] up to 2.4 million people living with chronic hepatitis B, and despite vaccinations and continued medical developments, the numbers haven’t changed appreciably over the past 15 years.”
The hepatitis B virus (HBV) can cause long-lasting liver infections that can set the stage for serious liver injury. When the virus infects liver cells, it introduces its DNA into the cell’s nucleus (where all genetic information is stored), and that viral DNA is used as a template for making more virus, allowing it to grow and spread in the liver.
Available antiviral therapies can reduce HBV levels in circulation, but cannot target the viral DNA in the cells of a patient to stop virus replication.
PBGENE-HBV is a gene-editing therapy designed to eliminate or inactivate all types of HBV DNA within the cell’s nucleus. In doing so, it may act as a functional cure for hepatitis B, according to Precision.
The ELIMINATE-B study plans to enroll 45 adults, ages 18 to 70, with chronic hepatitis B who are on stable regimens of antiviral therapies and test negative for HBeAg, a viral protein that indicates HBV is actively replicating.
The trial’s first part is sequentially testing three different PBGENE-HBV doses in three to six patients each. Each participant may receive up to three infusions at their assigned dose. Data from this part will be used to determine the optimal dose to be tested in the study’s second part, which will involve a larger number of patients.
The trial’s main goal is to assess PBGENE-HBV’s safety, while secondary goals include evaluating the therapy’s pharmacological properties and antiviral activity.
Early data suggest PBGENE-HBV was well tolerated
Early data from the first three trial participants, who had received the first infusion, suggested PBGENE-HBV was well tolerated, and that the therapy was exhibiting antiviral activity as designed. This was based on a substantial HBsAg level reduction in two of the three participants.
HBsAg is an HBV protein critical for the virus’s ability to infect cells and that can reflect disease activity.
“With a well-tolerated safety profile and early antiviral activity established after the first administration at dose level 1, Precision expects to complete subsequent administrations in all [group] 1 patients while in parallel expanding to the next higher dose [groups],” the release stated.
The observed drop in HBsAg levels was consistent with level reductions observed in preclinical non-human primate models of chronic hepatitis B, according to the company.
Additional safety data from these models, which were presented last week at the Global Hepatitis Summit 2025, supported a favorable safety profile for PBGENE-HBV. Notably, the gene-editing therapy did not accumulate throughout the body or reached germ cells (cells involved in reproduction), which suggests there’s not a risk the therapy could cause mutations that would be passed on to later generations.
In addition, studies in lab-grown, HBV-infected human liver cells demonstrated no increased risk of off-target effects — those on molecules other than the therapy’s targets — with additional dose administrations.
In a separate press release, Abramson said these preclinical data “highlight the potential to safely administer repeated doses of PBGENE-HBV … to achieve durable functional cures in chronic hepatitis B patients.”
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