PBGENE-HBV Granted FDA Fast Track Designation for Chronic Hepatitis B

The FDA granted a fast track designation to PBGENE-HBV (Precision BioSciences), an in vivo gene editing program designed to treat chronic hepatitis B through the elimination of covalently closed circular DNA (cccDNA). Currently, the treatment is undergoing evaluation in the ongoing phase 1 clinical trial, ELIMINATE-B (NCT06680232).^1,2

PBGENE-HBV, an in vivo gene editing program under investigation in a global, first-in-human clinical trial, is designed to potentially cure chronic hepatitis B infection. It is estimated that about 300 million people worldwide are afflicted with chronic hepatitis B. Hepatitis B is a leading cause of morbidity in the US and death globally, and despite the availability of approved antiviral therapies, an estimated 15% to 40% of patients with HBV infections may develop complications, such as cirrhosis, liver failure, or liver cancer (hepatocellular carcinoma), which account for the majority of hepatitis B virus-related deaths. If successful, PBGENE-HBV would be the first and only potentially curative gene editing program that is specifically designed to eliminate cccDNA and inactive integrated hepatitis B virus DNA.^1,3

ELIMINATE-B Clinical Trial

ELIMINATE-B is an open-label, dose escalation, dose expansion phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of PBGENE-B in adult patients with chronic hepatitis B. Patients were enrolled if they met the following criteria: male or female of nonchildbearing potential; body mass index of 18.0 to 35.0; were in good overall health (as deemed by the study Investigator); chronic hepatitis B infection documented at least 12 months prior to screening; hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B; and were virologically suppressed on current nucleos(t)ide analogue treatment.²

All participants will receive a finite course of multiple intravenous (IV) dose administrations of PBGENE-HBV. In part 1, administration will be conducted in a dose escalation manner, which may be further evaluated in a part 2 expansion cohort, noted the investigators. The ELIMINATE-B trial is designed for 3 dose administrations at each dose level, with the goal to maximize cumulative viral editing in order to achieve undetectable levels of hepatitis B surface antigen (HBsAg). The primary end point is frequency of treatment-emergent adverse events (TEAEs), which will be assessed 4 weeks following the final dose. Secondary end points include additional safety, pharmacokinetics, and antiviral activity of both hepatitis B virus DNA and HBsAg.²

Early Results

Initial results from the first administration of PBGENE-HBV (0.2 mg/kg) in cohort 1 of the ELIMINATE-B trial was safe and well-tolerated in all 3 patients. The investigators acknowledged that all 3 participants had different baseline characteristics, including age of infection, duration of infection, and level of HBsAg. Additionally, across the 3 participants dosed, none experienced a grade 2 or higher TEAE or serious AE.⁴

In addition to safety, PBGENE-HBV also showcased a substantial reduction in HBsAg in 2 of the 3 participants following the first administration at dose level 1. With a well-tolerated safety profile and early antiviral activity established at prespecified timepoints, the experts noted that all subsequent administrations in all cohort 1 patients would be completed. Further clinical data are expected to be announced throughout 2025, the experts said.⁴

“We are pleased to receive [a] fast track designation from the FDA for PBGENE-HBV and believe this classification underscores the urgent need for improved treatment options for patients living with chronic hepatitis B,” said Michael Amoroso, president and CEO at Precision BioSciences, in a news release. “We’ve been encouraged by the initial safety and antiviral activity we have observed in the ELIMINATE-B trial and look forward to continuing to work closely with the FDA as we progress PBGENE-HBV through clinical development.”¹

REFERENCES

1. Businesswire. Precision BioSciences Receives U.S. FDA Fast Track Designation for PBGENE-HBV, a First-In-Class Gene Editing Therapy Designed to Eliminate the Root Cause of Chronic Hepatitis B. April 17, 2025. Accessed April 17, 2025. https://www.businesswire.com/news/home/20250415414433/en/Precision-BioSciences-Receives-U.S.-FDA-Fast-Track-Designation-for-PBGENE-HBV-a-First-In-Class-Gene-Editing-Therapy-Designed-to-Eliminate-the-Root-Cause-of-Chronic-Hepatitis-B

2. Phase 1 Study to Evaluate Safety and Antiviral Activity of PBGENE-HBV in Adult Patients with Chronic Hepatitis B (ELIMINATE-B). ClinicalTrials.gov identifier: NCT06680232. Updated February 10, 2025. Accessed April 17, 2025. https://clinicaltrials.gov/study/NCT06680232

3. Precision BioSciences. PBGENE-HBV for Treatment of Chronic Hepatitis B. Accessed April 17, 2025. https://precisionbiosciences.com/pbgene-hbv/

4. Precision BioSciences. Precision BioSciences Announces Initial Safety and Antiviral Activity of PBGENE-HBV in the ELIMINATE-B Clinical Trial. News release. February 19, 2025. Accessed April 17, 2025. https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-announces-initial-safety-and-antiviral