FDA clears Precision BioSciences to begin trials of gene-editing treatment for hepatitis B
By Nancy La Montagne | This article originally appeared via NCBiotech's blog
Durham-based Precision BioSciences Inc. has received investigational new drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for PBGENE-HBV, an in vivo gene editing program designed to cure chronic hepatitis B virus (HBV) infection. It is the first investigational in vivo gene editing therapy for treating chronic hepatitis B to be cleared for clinical trials in the U.S.
Over a million people in the U.S. have chronic hepatitis B, and while antiviral treatments can suppress the virus and reduce liver damage, they don’t fully eliminate the infection. PBGENE-HBV addresses this challenge by targeting the main source of HBV replication and deactivating integrated HBV DNA in liver cells.
“IND clearance to expand the ELIMINATE-B trial for chronic hepatitis B is a first for the gene editing space,” said Michael Amoroso, president and CEO of Precision BioSciences. “This marks the advancement of potentially curative gene editing modalities into major markets for diseases where enormous global disease burden and lack of curative options have unfortunately become the norm.”
Advancing gene-editing for HBV
Precision BioSciences spun out of Duke University in 2006 and went public in March 2009. The company uses its proprietary ARCUS technology, which was discovered by company scientists, to develop new gene-editing therapies. ARCUS uses a naturally occurring genome editing enzyme, I-CreI, that evolved in algae to insert, remove, or repair the DNA of living cells and organisms.
The PBGENE-HBV therapy is based on an ARCUS-encoding mRNA encapsulated in a lipid nanoparticle to potentially eliminate the key source of replicating HBV, known as cccDNA, while also inactivating integrated HBV DNA in liver cells.
PBGENE-HBV is being clinically investigated in the ELIMINATE-B study, which tests the therapy at increasing dose levels, with three dose administrations per dose level in patients with chronic Hepatitis B who are HBeAg-negative. The study enrolled patients in Moldova, Hong Kong, and New Zealand. With the FDA IND clearance, Precision BioSciences will soon initiate Phase 1 clinical activities in the U.S at the Liver Center at Massachusetts.
Initial clinical results
In February, Precision BioSciences reported initial safety and antiviral activity from the ELIMINATE-B study. The study showed that PBGENE-HBV was safe and well-tolerated in all three participants in cohort 1 following the first dose administration at the lowest dose level. Substantial antiviral activity was also measured, as seen by the reduction of Hepatitis B surface antigen after one administration of the lowest dose level.
“Prior to commencing the ELIMINATE-B clinical trial, we conducted numerous preclinical studies with PBGENE-HBV to understand the pharmacokinetics, safety, and impact on viral markers at various dose levels and following multiple dose administrations. Importantly, the early data in the first cohort of patients is consistent with the safety and HBsAg reductions observed in our preclinical models,” said Cassie Gorsuch, PhD, chief scientific officer. “The safety and early reduction of HBsAg suggests that PBGENE-HBV is doing what no previous treatment has been able to accomplish, eliminating the source of viral replication in cccDNA and inactivating integrated disease.”
