Biotech Company Takes a Hit After Axing HBV Therapy over Safety Concerns

Stocks down

Shares of Assembly Biosciences have fallen more than 20% in premarket trading after the company announced it has discontinued developing a hepatitis B therapeutic candidate following the observation of elevated alanine transaminase (ALT levels) that are consistent with drug-induced hepatotoxicity.

John McHutchison, A.O., M.D., chief executive officer of South San Francisco-based Assembly Biosciences, said the decision to discontinue the development of the asset was an easy one to make because patient safety is the top priority of the company. McHutchison said the company remains committed to developing curative therapies for chronic hepatitis B. Despite the discontinuation of ABI-H2158, which was assessed in a Phase II study, he said the company’s strategy remains unchanged.

“We will continue to evaluate our core inhibitor portfolio, to ultimately choose the best and safest candidate to take forward into later stage clinical trials as we believe this mechanism will be an important and key component of future curative regimens,” McHutchison said in a statement.

Chronic hepatitis B virus (HBV) infection affects approximately 270 million people across the globe, based on estimates from the World Health Organization. HBV has a higher morbidity and mortality rate than hepatitis C. HBV is a leading cause of chronic liver disease and the need for liver transplantation. Up to one million people worldwide die every year from HBV-related causes.

ABI-H2158 was assessed in a mid-stage clinical trial for treatment-naïve patients with HBeAg positive or HBeAg negative chronic hepatitis B infection without cirrhosis. In the clinical trial, two patients who received 2158 experienced Grade 4 elevations in ALT, leading to drug discontinuation. Two additional patients who received 2158 developed Grade 3 ALT elevations. Elevated levels of ALT can lead to damage of liver cells, particularly in the liver. The company said the patients are being monitored for the elevated levels.

While the company was forced to discontinue ABI-H2158, Assembly Biosciences maintains a pipeline of core inhibitor candidates. Its most advanced candidate is vebicorvir, which has demonstrated a favorable safety and potent antiviral profile. Assembly is assessing vebicorvir in two ongoing triple combination studies. Initial treatment data for these trials are anticipated in 2022. Another clinical asset is ABI-H3733, which completed a Phase Ia study. According to the company, initial data from that trial will be shared at an upcoming conference.

Another asset is ABI-4334, also a core inhibitor, which will enter clinical studies in 2022. The company said ABI-4334 has a best-in-class preclinical profile for HBV.

“We remain focused on expeditiously advancing our additional clinical programs, including the two ongoing Phase II triple combination studies, accelerating the clinical development for 3733 and 4334, and progressing additional research programs in our HBV portfolio with complementary mechanisms. And, as always, we will continue evaluating strategic opportunities to build additional value in the company’s pipeline,” McHutchison added.

Funds used for the development of ABI-H2158 will be redirected into the other clinical programs.

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