At the 2022 European Liver Conference (EASL2022), Chinese researchers introduced the latest results of the phase 2b interim study in subjects with chronic hepatitis B who received subcutaneous PD-L1 Ab ASC22 (Envafolimab) + nucleosides for 24 weeks.
ASC22, a new drug under development for hepatitis B, combined with nucleosides, has released the latest phase 2b interim data.
Researchers believe that blocking the PD-1/PD-L1 pathway can restore the function of T cells and is expected to cure chronic hepatitis B (CHB). ). Hepatitis flares/flares (transient rebound) are thought to be primarily immune-mediated and may be associated with or mark a transition to reduced or even clearance of hepatitis B surface antigen (HBsAg) levels.
Previous studies have shown that interferon (PegIFN) treatment may cause ALT flares in 18-24% of patients because interferon is an immunomodulator. However, small interfering RNA (siRNA), a direct-acting antiviral drug, causes ALT flares in only 6% of patients. At this European Liver Congress, researchers report the characteristics of ALT flares and their association with HBsAg reduction, serum clearance and seroconversion from a 24-week subcutaneous PD-L1 antibody ASC22+ nucleoside-based 2b study on CHB. Interim analysis of phase 1 clinical trials.
This randomized, single-blind, multicenter phase 2b clinical trial was divided into two cohorts and enrolled a total of 149 subjects with chronic hepatitis B (hepatitis B e antigen negative, surface antigen ≤ 10000 IU/mL and HBVDNA20 IU/mL ), they received 24 weeks of ASC22 treatment (1 or 2.5 mg/kg) and 24 weeks of follow-up (clinical trial number: NCT04465890).
Analysis of the relationship between ALT flare and hepatitis B surface antigen reduction/disappearance in subjects who completed 24 weeks of 1 mg/kg ASC22 Q2W (n=33) or placebo PBO Q2W (n=11) + nucleosides (NAs). relationship between. ALT A sudden increase in ALT is defined as a transient increase in serum ALT more than 3 times the baseline level and more than 2X ULN (upper limit of normal).
Results showed that baseline serum HBsAg, ALT and AST levels were comparable in subjects receiving ASC22 or placebo + nucleoside. Seven subjects had a 0.5 log10 IU/mL reduction in HBsAg, and all had baseline HBsAg ≤ 500 IU/mL. Three subjects even experienced HBsAg serologic clearance (undetectable, 0.05 IU/mL).
from the European Liver Conference 2022
One subject who lost HBsAg experienced hepatitis B surface antibody (HBsAb) seroconversion 6 weeks after the last ASC22 dose (Figure 1A above). ALT flares were observed in 5/33 (15%) subjects in the ASC22 group but not in the placebo group. Among subjects whose HBsAg decreased by 0.5 log10 IU/mL or whose HBsAg disappeared, ALT flares occurred in 4/7 (57%) and 2/3 (67%) subjects, respectively (Figure 1B above).
No clinically significant changes in total bilirubin or direct bilirubin were observed in subjects with ALT flare-ups. However, more immune-related adverse events (irAEs) occurred in the ASC22 group. The most common irAEs were grade 1 ALT/AST elevation and rash.
In summary, the researchers gave this phase 2b interim conclusion that the ALT flare that occurred during ASC22 treatment proved to be a clinically meaningful indicator of immune response, leading to a significant reduction in HBsAg levels and subsequent HBsAg loss/HBsAb. Seroconversion.
Xiaopan Health Conclusion: This is also a relatively positive research progress brought by Chinese researchers at this European Liver Conference. Simply put, in the ASC22+ nucleoside group, it was observed that 7 subjects had hepatitis B The surface antigen level decreased by 0.5 log10 IU/mL, and 3 out of 7 patients achieved sustained hepatitis B surface antigen clearance! The Phase 3 study of
ASC22 has not yet officially started and is expected to be released sometime in 2022. In addition, ASC22 has approved indications not only for HBV, but also for HIV. Recently, China's phase 2 clinical trial of ASC22+ retroviral therapy (ART) for HIV-1 has completed the administration of the first subject. The endpoint of the study is the same as that of chronic hepatitis B, which is to achieve functional cure of HBV/HIV. Ascletis Pharmaceuticals’ comments on the new data submitted by ASC22 at this European Liver Conference will be introduced in detail in another article.
