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VTP-300 as a monotherapy and in combination with a single administration of low-dose nivolumab was administered, with no treatment-related serious adverse events and infrequent transient transaminitis.
Meaningful, durable reductions of Hepatitis B surface antigen (HBsAg) were seen in some patients who received VTP-300 as either a monotherapy or in combination with a single low dose of nivolumab at the booster dose. Declines were most prominent in patients with lower baseline HBsAg.
All patients who received VTP-300 monotherapy or in combination with low-dose nivolumab and who had a HBsAg decline greater than 0.5 log10 had durable reductions of HBsAg until the last measurement (up to eight months after last dose).
A robust T cell response against all encoded antigens, measured by overnight stimulation, was observed following VTP-300 administration, notably for marked CD8+ T cell predominance, which, to our knowledge, has never been achieved by any other immunotherapeutic.
OXFORD, United Kingdom, June 22, 2022 (GLOBE NEWSWIRE) -- Vaccitech plc (NASDAQ: VACC), a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, cancer, and autoimmune diseases, today announced an update to the interim analysis of safety and efficacy data from the HBV002 study (NCT04778904), which is being presented as a poster at the 2022 EASL International Liver CongressTM by Professor Ellie Barnes, Professor of Hepatology and Experimental Medicine at the University of Oxford.
The updated analysis, with a data cut-off of May 9th, which now includes 39 patients with at least three months of follow-up, shows that VTP-300 as a monotherapy or in combination with a single low-dose nivolumab at the time of the booster dose was safely administered with no treatment-related serious adverse events and two patients with mild, rapidly resolving transaminitis.
In the VTP-300 monotherapy group, meaningful and durable reductions of HBsAg were seen in all three patients with baseline HBsAg under 50 IU/mL. These three patients had 0.7, 0.7 and 1.4 log10 declines two months after the last dose of VTP-300. These dramatic declines have persisted in all three patients at their latest follow-up at five or eight months after the last dose of VTP-300.
For the first eight patients who received VTP-300 in combination with a single low-dose of nivolumab at the time of the booster dose, the mean reduction in HBsAg was over 1 log10 at six months, an effect that persisted, with a mean decline of 1.15 log10 at eight months after the last dose of VTP-300. The effect was most prominent in patients with baseline HBsAg lower than 1,000 IU/mL. One patient in this group developed a non-detectable HBsAg level, which continued eight months after the last dose of VTP-300.
No reductions ≥1 log10 were seen in patients who received two doses of MVA-HBV, or in patients who received low-dose nivolumab with both doses of VTP-300. These two groups were discontinued after interim analysis.
“The immune system is likely a needed component in achieving durable HBsAg loss that could lead to a functional cure for patients with chronic hepatitis B (CHB),” said Dr. Henry Chan, Honorary Clinical Professor, Faculty of Medicine, The Chinese University of Hong Kong. “This exciting initial data supports VTP-300’s potential as an immunotherapy that can stimulate an antigen-specific immune response and could be a critical component of a functional cure regimen. I look forward to following future clinical and combination developments.” Dr. Henry Chan is a scientific advisor to Vaccitech but not directly involved in the HBV002 study.
A robust T cell response against all encoded antigens (core protein, polymerase and surface antigen), measured by overnight stimulation, was observed following VTP-300 administration, notable for marked CD8+ T cell predominance.
“The robust T cell response and marked, durable HBsAg reduction eight months after VTP-300 administration is remarkable,” said Thomas Evans, M.D., Chief Scientific Officer of Vaccitech. “We believe the prominent effect we are observing in patients with lower starting HBsAg levels supports the collaborative study with Arbutus Biopharma’s siRNA, AB-729, in which HBsAg has shown to be lowered below 100 IU/mL in a majority of treated patients.”
Enrollment in the HBV002 study is complete with 55 patients enrolled. An updated interim analysis for all patients at the six month follow-up timepoint is expected at the end of 2022.
A trial to look at timing of low dose nivolumab and additional doses of the MVA boost component of VTP-300 (NCT05343481) is planned in multiple countries, with the first patient expected to be dosed in the third quarter of 2022.
HBsAg is a hallmark of chronic hepatitis B virus (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. The crux of chronic HBV is the immune system’s inability to clear the virus due to insufficient immune priming and/or aberrant immune tolerance due to large quantities of HBV protein expression. Many involved in the field believe it makes sense to combine an immune-stimulating agent with an HBV protein-suppressing agent, to potentially elicit a functional cure to HBV.
Presentation details
Poster Title: Phase 1b/2a study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with CHB on nucleos(t)ide analogues
Poster Number: SAT-428
Presenter: Ellie Barnes, Professor of Hepatology and Experimental Medicine, Nuffield Department of Medicine, University of Oxford
Abstract: 3328
About HBV002
HBV002 is an open-label trial designed to evaluate 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 suppressed HBV DNA on nucleos(t)ide therapy.
As of June 22, 2022, 55 patients have been enrolled, and no concerning safety signals or vaccine-related serious adverse events have been reported.
Data from a previous interim analysis of HBV002 presented at the AASLD The Liver Meeting® in November 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.
About VTP-300
VTP-300 is a novel immunotherapy, dosed in a prime-boost regimen, whereby the immune system is primed with an adenovirus (ChAdOx1) and boosted with a pox virus (MVA). Both vectors have been modified to improve safety, enhance the immune response they induce and include HBV specific antigens including core, polymerase and surface antigen. Clinical data generated to date has demonstrated this regimen to be generally safe and well-tolerated, that antigen specific T cell responses are stimulated to each antigen and there were meaningful reductions in hepatitis B surface antigen when this regimen is given alone or when given in combination with a low dose of nivolumab at the boost. |
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发表于 2022-6-23 16:21
