Hepatitis B drug developer Assembly Biosciences is Lopsided After four patients showed signs of potential liver problems in mid-term clinical trials, an experimental treatment was studied. Although the research has been discontinued, Assembly continues to monitor patients, while also shifting its focus to other hepatitis B drugs in its development.
The worrying indicator is alanine aminotransferase, a liver enzyme whose elevated levels are consistent with drug-induced liver toxicity. Assembly Bio has not yet clearly linked its drug ABI-H2158 to these liver enzymes. But the South San Francisco-based biotechnology company also said that it has not found other reasons for the increase in enzyme levels. The company has notified the FDA that the agency said the drug will be placed on clinical suspension.
ABI-H2158 is a drug called a core inhibitor by the company. The small molecule is designed to target the core protein, a viral structural protein of the hepatitis B virus, which has no human counterpart and is involved in many aspects of the virus replication cycle.
The Phase 2 study of ABI-H2158 enrolled 88 patients who were randomly assigned to receive Assembly Bio drug plus hepatitis B antiviral drug entecavir, or placebo plus entecavir. This regimen is administered once a day for up to 72 weeks. Assembly Bio stated that the liver enzyme levels of two patients in the ABI-H2158 group reached a grade 4 adverse event, life-threatening or disabling. Those patients stopped treatment. Two other patients had liver enzyme levels of grade 3, which was considered serious.
Assembly Bio’s drug pipeline has additional core inhibitors, the most advanced of which is called vebicorvir. So far, the antiviral drug has shown good safety and effectiveness in phase 2 clinical trials for patients treated for up to 18 months. The company stated that it believes that combination therapy is the key to finding a cure for hepatitis B infection and is evaluating two triple combinations of vebicorvir with currently available treatments and experimental treatments. Preliminary data is expected next year.
Another core inhibitor, ABI-H3733, has completed phase 1a testing, and the company plans to report preliminary data at an upcoming medical meeting. Another core inhibitor, ABI-4334, is expected to undergo clinical trials next year. In pre-clinical studies, Assembly Bio stated that this compound has shown its potential to become the best drug in its class. The company also pointed out that ABI-H3733 and ABI-4334 are structurally different from the discontinued ABI-H2158.
Assembly Bio stated that the reallocation of resources from the terminated hepatitis B project should help accelerate the development of other assets, while also extending the amount of cash available to support its research to the second half of 2023. As of June 30, according to Assembly’s financial report for the second quarter of 2021, Bio’s cash and cash equivalents were $59.7 million.
Assembly Bio has been trimming its pipeline. The company has collaborated with Allergan on microbiome drug research, and the alliance dates back to 2017. After Allergan was acquired by AbbVie last year, the company carried out its own pruning and decided to terminate the partnership. Restitution rights To the microbiome program. Assembly Bio looked around for assets, but did not find a bidder. At the end of last year, Assembly Bio’s board of directors decided to terminate the microbiome plan and focus the company on hepatitis B drug research.
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