Aligos Takes Another Hit with Halt of Chronic Hepatitis B Therapy
Aligos halted the production of therapy for Chronic Hepatitis B.
Aligos Therapeutics, headquartered in South San Francisco, halted development of ALG-020572, which was being developed in patients with chronic hepatitis B (CHB). The first CHB cohort of Study ALG-020572-401 was stopped after one of the patients had a serious adverse event (SAE) causing a brief hospitalization.
The patient showed a significant increase in alanine aminotransferase (ALT) after multiple dosing of 210 mg of the therapy. Aligos noted that this was just one of four chronic hepatitis B (CHB) subjects in the cohort to have the potentially drug-related ALT flares, indicative of liver toxicity, which it was not expecting based on nonclinical research and Phase I studies in healthy volunteers.
What does Aligos Said About the Hiatus on Chronic Hepatitis B Therapy?
“Patient safety is our number one priority, and we are gratified to see that these unanticipated ALT elevations are improving, and subjects are on the path to recovering,” said Lawrence M. Blatt, Aligos’ chairman and chief executive officer. “We will continue to follow emerging safety and antiviral activity data as these subjects complete their off-treatment follow-up to understand these events further. Although this is undeniably a setback, our team remains committed to developing drug candidates with the potential to improve the lives of patients living with viral and liver diseases.”
ALG-020572 is a GalNAc-conjugated antisense oligonucleotide (ASO). The theory behind ASOs is small pieces of DNA or RNA can bind to specific RNA molecules which then block the RNA from producing a specific protein that is needed for a specific disease.
The company indicated that it was going to shift its resources to other clinical programs, specifically ALG-000184 in chronic hepatitis B (CHB), ALG-055009 being developed for hyperlipidemia, ALG-125755 for hepatitis B, and a ritonavir-free oral, highly potent SARS-CoV-2 protease inhibitor to treat COVID-19.
Blatt also said, “We will focus on accelerating our internal oral small molecule preclinical development programs, including: a Class-I CAM for chronic hepatitis B (CHB); and a PD-L1 inhibitor for CHB. Finally, we remain committed to our external partners in the oligonucleotide space, including Merck with whom we are collaborating on certain undisclosed targets for NASH.”
As a result of this shift, the company believes it will have enough cash, cash equivalents and investments to operate into the first half of 2024.
This is the second major hit this year for the company. On Jan. 6, 2022, it announced it was halting the development of ALG-010133, its STOPS drug candidate, for chronic hepatitis B (CHB). At that time, Aligos said emerging data from the Phase I study showed the drug at 400 mg was unlikely to produce meaningful hepatitis B viral antigen reduction. It did not identify any dose-limiting safety findings.
At the time, Blatt said, “We are disappointed that the antiviral activity data from this study indicate that ALGL-010133 cannot meaningfully contribute to achieving functional cures in chronic hepatitis B (CHB). Hepatitis B is a very challenging virus that will require combination regimens involving distinct mechanisms of action (MOAs) in order to achieve a functional cure.”
Shortly afterward, on Jan. 11, Aligos announced it was expanding its ongoing collaboration with Merck for nonalcoholic steatohepatitis (NASH). NASH is similar to cirrhosis of the liver but occurs in people who drink little or no alcohol. Under the original deal, the companies were applying Aligos’ oligonucleotide platform technology to find and develop oligonucleotides against a certain undisclosed NASH target and up to one more target of interest in the cardiometabolic/fibrosis space.
They expanded it to include the in-license by Merck of an early-stage program related to a second undisclosed NASH target that Aligos has been working on separately and independently from Merck. The expansion also added a potential third target in the same broad space.