Precision reports mixed early results for hep B gene editing therapy

Precision BioSciences has shared phase 1 low-dose and safety data for its lead in vivo gene editing program, designed to effectively cure chronic hepatitis B.

The ELIMINATE-B trial is designed to investigate PBGENE-HBV at multiple ascending dose levels with three dose administrations per level in patients afflicted with chronic hepatitis B who are Hepatitis B e-Antigen (HBeAg)-negative, treated daily with nucleos(t)ide analog therapies, and have ≥200 IU/mL HBsAg without an upper limit.

The recently-shared study data included a completed Cohort 1 — the lowest dose level of the trial — and initial safety data from Cohort 2.

Cohort 1 of the study consisted of three patients, each of whom received three planned administrations of PBGENE-HBV dosed approximately eight weeks apart. While one patient achieved durable undetectable levels of HBsAg (a marker for active infection) seven months after dosing, the other two patients in Cohort 1 demonstrated antiviral response after each dose administration but returned to baseline levels of HBsAg.

In Cohort 2, consisting of three patients, no adverse events above Grade 2, no serious adverse events, nor dose-limiting toxicities were observed.

“Our early data shows that we have a novel, safe and active drug in all patients treated, with a durable effect in one-third of patients, even at the lowest dose level. To deliver a complete cure and reduce long term liver disease and cancer risk, we must ensure we are eliminating the root cause of disease replication – the cccDNA. We are generating molecular data using liver biopsies to demonstrate PBGENE-HBV’s mechanism of action to eliminate cccDNA and inactivate integrated HBV DNA,” said Michael Amoroso, president and CEO of Precision.

Given the favorable safety profile in Cohort 1 and 2, Precision said it will begin enrolling Cohort 3 this month to test the next higher dose level.

The U.S. FDA has granted fast track designation to the therapy back in April, and the company has clinical investigation underway in the U.S., Moldova, Hong Kong, New Zealand, and the UK.