Vaccitech reports promising interim efficacy analysis in Phase 1b/2a clinical study in chronic HBV

Vaccitech reports promising interim efficacy analysis in Phase 1b/2a clinical study in chronic HBV

Interim data from 27 patients, who had completed 3 months in the HBV002 study in chronic Hepatitis B (CHB) patients, demonstrated noted changes in surface antigen (HBsAg) levels, especially in the group receiving low-dose nivolumab with the heterologous boost (VTP-300).

The HBV002 study is enrolling 4 groups to explore prime-boost vector combinations, either MVA-HBV (prime) + MVA-HBV (boost), ChAdOx1-HBV (prime) + MVA-HBV (boost) (VTP-300), VTP-300 with low-dose nivolumab given at the boost, and VTP-300 with low-dose nivolumab given at both the prime and the boost.

The HBV002 study is designed to evaluate the different regimens and investigators will now look to focus enrollment on Group 2 which involves dosing of VTP-300 without nivolumab and Group 3, which involves dosing of VTP-300 with nivolumab administered with the MVA boost, due to the encouraging surface antigen (HBsAg) decrease measured in these study groups.

OXFORD, United Kingdom, Dec. 7, 2021 -- Vaccitech plc (NASDAQ: VACC), a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines, today announced a promising interim analysis of safety and efficacy data from the HBV002 study, including a review of surface antigen (HBsAg) levels in CHB patients.

Data from an interim analysis of immunogenicity and safety in Groups 1 and 2 were recently reported at the 2021 AASLD The Liver Meeting®, and a broader efficacy data set has now been analyzed, including patients receiving VTP-300 in combination with low-dose nivolumab (Groups 3 and 4).

The company has concluded that the results support a protocol change that will lead to a focus on enrolling patients into Groups 2 and 3.

The analysis of Group 3, patients on antivirals for at least 12 months with undetectable HBV DNA and a mean starting HBsAg level of 441 IU/ml, showed:

• Mean of greater than one log decrease (-1.04) and a greater than one log decrease in HBsAg in 3/6 patients at 3 months.
• HBsAg in one patient was undetectable 3 months after starting the immunotherapy regimen.
• One patient with a decrease experienced a transaminase flare after the MVA boost plus nivolumab that resolved over 3 weeks.
• Despite the very small patient numbers the difference in mean HBsAg between Group 3 and the other groups was highly significant (p < 0.01).

In addition, in the VTP-300 group without nivolumab (Group 2), one patient had a 1.29 log and one patient had a 0.70 log decrease at month 3 (2/6).

Enrollment into HBV002 will continue into 2022 and a further interim analysis, including more HBsAg level data, is anticipated during the first half of 2022.

“These interim efficacy results of the ongoing HBV002 study are very promising and build upon recent safety and T cell immunogenicity data from Groups 1 and 2 that were presented at AASLD this year,” said Thomas Evans, M.D., Chief Scientific Officer of Vaccitech. “The new analysis showed that some patients on chronic antivirals receiving VTP-300 alone, as well as in combination with a low-dose checkpoint inhibitor, experienced meaningful decreases in HBsAg levels.”

HBsAg is a hallmark of chronic HBV infection. Fewer than 10% of patients on current standard of care HBV therapies ever achieve distinct, sustained HBsAg decrease or loss, a state associated with functional cure of the disease.

Data from a previous interim analysis of HBV002 showed that VTP-300 was well-tolerated in CHB patients and that induced T cells were shown to be cross-reactive to two major HBV genotypes (C and D).

About HBV002

HBV002 is an open-label trial to determine the safety, immunogenicity and preliminary efficacy of ChAdOx1-HBV and MVA-HBV (VTP-300), with or without low-dose nivolumab, in patients with chronic HBV with supressed HBV DNA on nucleos(t)ide therapy.

As of December 6^th, 2021, 33 patients had been enrolled, and no concerning safety signals or Serious Adverse Reactions have been reported.

Data presented at the AASLD The Liver Meeting® in October 2021 showed that VTP-300 induced antigen specific T cell responses to all antigens, with elevated responses to core and polymerase, as compared to healthy controls dosed with ChAdOx1-HBV alone in HBV001, who exhibited a greater response to surface antigen. As in the HBV001 results, T cell responses cross-reactive to Genotype D specific peptides were measured in the majority of patients.