Arbutus cans early-phase hep B program after 2 healthy people fall ill

Arbutus Biopharma is dumping one of its Roivant-backed programs after two healthy people in a phase 1 study developed acute hepatitis—the very disease the drug was supposed to treat. 

The company was developing the drug, an oral capsid inhibitor called AB-506, for the treatment of chronic hepatitis B, where patients can’t clear the virus after six months. The drug is designed to attack the capsid, or protein shell, that protects the virus’ genetic material, thereby blocking viral replication. 

In July, Arbutus reported data from 33 healthy people and 24 patients with chronic hepatitis B showing that after 28 days of treatment, neither group experienced serious side effects. The study tested two doses of the drug and found that both slashed virus levels at similar rates to other capsid inhibitors in development. 

Then, two healthy people developed hepatitis. 

“We have observed two cases of acute hepatitis in our Phase 1a 28-day clinical trial in healthy volunteers. Consequently, the clinical trial and further development of AB-506 have been stopped,” said Arbutus CEO William Collier in a statement. The company is canceling a combination study of AB-506 and its lead asset, AB-729, an RNAi treatment for hep B that was slated to start in 2020. 

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The patients are being treated for and “experiencing resolution” of their acute hepatitis, added Gaston Picchio, Ph.D., Arbutus’ chief development officer. Though the company canned the AB-506 program, it will still present data from the phase 1a/1b study, including more details about the two hepatitis cases, at a scientific meeting later this year, Picchio said. 

Arbutus’ bench is deep, according to Chief Scientific Officer Michael Sofia, Ph.D.—“While we are disappointed in these recent clinical findings, we have a number of oral follow-on capsid inhibitor compounds with distinct chemical scaffolds that we believe have the potential to contribute to the inhibition of HBV replication as part of a combination regimen. Our objective is to select one of several lead compounds for IND-enabling studies by December of this year.” 

The termination of AB-506 leaves only the RNAi drug AB-729 in Arbutus’ clinical pipeline. It has an RNA destabilizer in IND-enabling studies. 

Roivant backed Arbutus in a $116 million share purchase deal two years ago on the heels of positive phase 2 data for the gene-silencing drug ARB-1467. One year later, in October 2018, the drug turned up disappointing data: Of the six patients enrolled in the phase 2 study, three didn’t mount enough of a response after six weeks of treatment to move onto the next stage of treatment. 

The pair also set up Genevant, an RNA-focused joint venture, early last year, wit RNA delivery technology from Arbutus and $37.5 million in seed funding from Roivant. It plans to take five to 10 programs into the clinic by 2020.