Antios Therapeutics received a clinical hold on its Hepatitis B virus (HBV) combinatorial therapy from the U.S. Food and Drug Administration on Wednesday.
Antios Therapeutics received a clinical hold on its Hepatitis B virus (HBV) combinatorial therapy from the U.S. Food and Drug Administration on Wednesday. The action has resulted in the termination of a collaboration agreement between Antios and Assembly Biosciences.
Antios was in two collaborative deals for its therapeutic ATI-2173, an oral drug candidate for chronic HBV. In December 2021, Antios and Arbutus Biopharma announced that the first patient was dosed in a Phase IIa combination trial of ATI-2173 and AB-729, an RNA interference therapeutic. In October 2021, Antios and Assembly Biosciences entered into a clinical collaboration agreement to evaluate ATI-2173 and vebicorvir, an HBV core inhibitor, as a combinatorial treatment for chronic HBV infection.
Now, Assembly has chosen to cut ties with Antios over the clinical hold. In a regulatory filing, Assembly stated that Antios notified the company of the clinical hold, which was established based on a safety report involving a patient who received a triple combination therapy and a nucleos(t)ide analog reverse transcriptase inhibitor.
Antios CEO Greg Mayes told Fierce Biotech that the company does not believe the adverse event to be related to the therapy, but that the FDA has requested an independent cardiology review of the asset.
It does not seem that the deal between Antios and Arbutus is off the table yet, though. The two companies are investigating a different combinatorial treatment than the one which was penned with Assembly. The trial is investigating ATI-2173, AB-729 and tenofovir disoproxil fumarate in patients with chronic HBV infection. However, the clinical trial is bound to face similar setbacks as ATI-2173 undergoes investigation.
ATI-2173 is an investigational phosphoramidate prodrug of clevudine monophosphate. The drug works to curb HBV by inhibiting HBV polymerase, and Antios has stated previously that if the drug is approved, it could become the cornerstone of curative treatment for HBV. The mechanism of action behind ATI-2173 is designed to be complementary to other treatments seeking a curative approach to HBV, hence the collaborations. In studies of ATI-2173, a single oral dose demonstrated 82% hepatic extraction.
In the Assembly and Antios collaborative trials, ATI-2173 was to be paired with vebicorvir, Assembly’s lead core inhibitor and tenofovir disoproxil fumarate. In Phase II clinical trials, vebicorvir administered with nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy led to greater viral suppression of both HBV DNA and HBV pgRNA than NrtI therapy alone.
Assembly is also in collaborative cahoots with Arbutus Biopharma, testing vebicorvir in combination with AB-729 for patients with chronic HBV infection. The two entered into a collaboration agreement in August 2020, and Assembly recently announced that it anticipates completing enrollment for its clinical trial with Arbutus in the first half of 2022. Assembly is also investigating core inhibitor ABI-H3733 for HBV in a stand-alone monotherapeutic trial.
Chronic HBV infection remains an important target for innovative treatment. Although treatment with immune modulator drugs and antiviral drugs can slow down the risk of developing more serious liver disease, there is no complete cure for the condition which can cause cirrhosis, liver failure or liver cancer.
