Antios Therapeutics’ push to develop a curative hepatitis B therapy has hit turbulence. The FDA has slapped Antios with a clinical hold over a safety report, prompting Assembly Biosciences to terminate its clinical trial collaboration agreement with the deep-pocketed biotech.
Last year, Antios made a splash, pulling off back-to-back financing rounds collectively worth $171 million to fund work on its hepatitis B prospect ATI-2173. The drug candidate is a liver-targeted prodrug form of clevudine, an antiviral that Pharmasset advanced into phase 3 more than a decade ago only for cases of muscle weakness in long-term users to stop the program.
In between the two financing rounds, Antios entered into deals with Arbutus Biopharma and Assembly Bioscience to test ATI-2173 in combination clinical trials. Antios’ publicly traded partners were the source of the initial information on its setback.
“ATI-2173, Antios’s investigational proprietary active site polymerase inhibitor nucleotide, has been placed on clinical hold by the U.S. Food and Drug Administration following submission of a safety report,” Assembly said in a financial filing. The safety report involved a patient who received a triple combination of Antios’ ATI-2173, Assembly’s vebicorvir and a nucleotide reverse transcriptase inhibitor.
Assembly terminated the clinical trial collaboration agreement it formed with Antios last year because of the hold. Separately, Arbutus updated its corporate presentation. The update removed a phase 2 trial of a combination involving ATI-2173, Arbutus’ AB-729 and a nucleotide analog from the pipeline. Antios CEO Greg Mayes said "the Arbutus study was impacted by the Russian invasion of Ukraine and all dosing was completed and one patient remains in long term follow-up and the event observed in the Assembly study was not observed in the Arbutus study."
Mayes provided more information in an emailed statement: "The first patient in this study was dosed the triple combination of ATI-2173, TDF, and vebicorvir on April 27, 2022. Female patient (49 years old) experienced bradycardia and hypotension which appeared to be a vasovagal/presyncope event about 4 hours post dose. The patient was fasting for 20 hours, had high volume blood draws, and taken a diuretic (indapamide).
"We do not believe this to be a treatment-related adverse event; ATI-2173 was generally well-tolerated with no concerning safety signals. However, the investigator conducting the study believes the adverse event may have been treatment related to the triple combination regimen of ATI-2173, TDF and vebicorvir. Despite our conclusion that this is not a signal for cardiotoxicity, the FDA has requested an independent cardiology review of ATI-2173."
As of Jan. 15, 172 subjects had been exposed to ATI-2173. Mayes said Antios has seen "no evidence of cardiac safety signals associated with ATI-2173 or its metabolites."
Editor's note: This story was updated at 9:27 a.m. ET May 25 with a statement from Greg Mayes.